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1.
Clin Endocrinol (Oxf) ; 71(1): 145-53, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19178514

RESUMO

BACKGROUND: Critical illness results in activation of the hypothalamic-pituitary-adrenal (HPA) axis, which might be accompanied by a peripheral adaptation in glucocorticoid sensitivity. Tissue sensitivity is determined by the active glucocorticoid receptor GRalpha, of which two splice variants involving the hormone-binding domain exist, GRbeta and GR-P. OBJECTIVE: To study tissue mRNA expression of the GR and its splice variants in fatal critical illness. DESIGN AND METHODS: We assessed mRNA expression of the GRalpha, GRbeta and GR-P variants in liver (n = 58) and muscle (n = 65) of patients who had died after intensive care, and had been randomized for insulin treatment. We analysed whether GR mRNA expression was associated with insulin treatment, cortisol levels and glucocorticoid treatment. RESULTS: GRalpha and GR-P mRNA constituted 87 +/- 8% and 13 +/- 2%, respectively, of total GR mRNA in liver. GRbeta mRNA could only be amplified in five liver samples. All variants were present in most muscle samples (alpha = 96 +/- 11%, P = 3.9 +/- 0.4%, beta = 0.010 +/- 0.002%). GR expression was not associated with insulin therapy. A strong positive relationship was observed between the different GR variants in both liver and muscle (P < 0.001 for all). Serum cortisol levels were negatively associated with liver GRalpha and muscle GR-P expression (P < 0.05). mRNA expression of both liver GRalpha and GR-P, but not muscle GR, was substantially lower in patients who had received exogenous glucocorticoids (P < 0.01). CONCLUSION: We demonstrate the presence of GRalpha and GR-P mRNA in liver and of GRalpha, GRbeta and GR-P mRNA in muscle, with no evidence for altered splicing in critical illness. In contrast to muscle GR, liver GR expression was substantially lower in patients receiving exogenous glucocorticoids.


Assuntos
Processamento Alternativo , Estado Terminal/terapia , Expressão Gênica , Fígado/metabolismo , Músculos/metabolismo , Receptores de Glucocorticoides/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Glucocorticoides/uso terapêutico , Humanos , Insulina/uso terapêutico , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Receptores de Glucocorticoides/metabolismo
2.
J Clin Endocrinol Metab ; 82(9): 3068-73, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9284745

RESUMO

TRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2. TRH was undetectable in serum (< 25 pg/mL), but TRH-LI was detected with antiserum 4319 in serum of 27 normal subjects, 21 control patients, and 12 patients with carcinoid tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because serum was kept for at least 2 h at room temperature, which causes degradation of TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is not caused by these peptides. On high-performance liquid chromatography, serum TRH-LI coeluted with pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced in, among others, the prostate. Urine of normals and control patients also contained TRH-LI (range 1.14-4.97 and 0.24-5.51 ng/mL, respectively), with similar levels in males and females. TRH represented only 2% of urinary TRH-LI, and anion-exchange chromatography and high-performance liquid chromatography revealed that most TRH-LI in urine was < EEP-NH2. In patients with carcinoid tumors, increased urinary TRH-LI levels were noted (range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with urinary creatinine, and the urinary clearance rate of TRH-LI was similar to the glomerular filtration rate. In addition, serum TRH-LI was increased in 17 hemodialysis patients (43-373 pg/mL). This suggests that serum < EEP-NH2 is cleared by glomerular filtration with little tubular resorption. The possible role of the prostate as a source of urinary TRH-LI was evaluated in 11 men with prostate cancer, showing a 25% decrease in urinary TRH-LI excretion after prostatectomy (0.19 +/- 0.02 vs. 0.15 +/- 0.01 ng/mumol creatinine, mean +/- SEM). However, TRH-LI was similar in spontaneously voided urine and in urine obtained through a nephrostomy cannula from 16 patients with unilateral urinary tract obstruction (0.15 +/- 0.01 vs. 0.14 +/- 0.01 ng/mumol creatinine). These data indicate that: 1) TRH-LI in human serum represents largely < EEP-NH2, which is cleared by renal excretion; 2) part of urinary < EEP-NH2 is derived from prostatic secretion into the blood and not directly into urine; and 3) urinary < EEP-NH2 can be used as marker for carcinoid tumors.


Assuntos
Rim/metabolismo , Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/metabolismo , Adulto , Idoso , Anuria/sangue , Tumor Carcinoide/secundário , Tumor Carcinoide/urina , Cromatografia Líquida de Alta Pressão , Constrição Patológica , Creatinina/sangue , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Antígeno Prostático Específico/análise , Prostatectomia , Ácido Pirrolidonocarboxílico/análogos & derivados , Valores de Referência , Hormônio Liberador de Tireotropina/sangue , Hormônio Liberador de Tireotropina/urina , Doenças Urológicas/urina
3.
J Endocrinol ; 153(3): 411-21, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9203995

RESUMO

TRH-like immunoreactivity (TRH-LI) was estimated in methanolic extracts of rat tissues and blood by RIA using antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2, or antiserum 8880, which is specific for TRH (pGlu-His-ProNH2). TRH-LI (determined with antiserum 4319) and TRH (determined with antiserum 8880) contents were 8 and 8 ng/g in brain, 216 and 222 ng/g in hypothalamus, 6.5 and 6 ng/g in pancreas, 163 and 116 ng/g in male pituitary, 105 and 77 ng/g in female pituitary, 1 and 0.1 ng/g in salivary gland, 61 and 42 ng/g in thyroid, 12 and 3 ng/g in adrenal, 3 and 0.3 ng/g in prostate, and 11 and 0.8 ng/g in ovary respectively. Blood TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 31 and 18 pg/ml in male rats, and 23 and 10 pg/ml in female rats respectively. Unextracted serum obtained from blood kept for at least 1 h at room temperature no longer contained authentic TRH but still contained TRH-LI (males 20.3 +/- 3.1, females 15.9 +/- 3.0 pg/ml; means +/- S.E.M.). Isocratic reverse-phase HPLC showed that TRH-LI in serum is largely pGlu-Glu-ProNH2 (< EEP-NH2), a peptide previously found in prostate and anterior pituitary. In urine, TRH-LI (antiserum 4319) and TRH (antiserum 8880) levels were 3.21 +/- 0.35 and 0.32 +/- 0.04 ng/ml in male rats and 3.75 +/- 0.22 and 0.37 +/- 0.04 ng/ml in female rats respectively (means +/- S.E.M.). Anion-exchange chromatography on QAE-Sephadex showed that urine of normally fed rats contains both basic/neutral TRH-LI (b/n TRH-LI) and acidic TRH-LI (aTRH-LI) in a ratio of approximately 40:60, and further analysis by HPLC indicated that aTRH-LI represents < EEP-NH2. Analysis of food extracts and urine from fasted rats demonstrated that b/n TRH-LI is derived from food particles spilled by the rats during urine collection, while aTRH-LI is endogenously produced. While urinary aTRH-LI levels were higher in female than in male rats (2.99 +/- 0.41 vs 2.04 +/- 0.20 ng/ml), the daily urinary excretion was similar in both sexes (females 15.6 +/- 1.4, males 19.5 +/- 2.0 ng/day). Intravenously injected < EEP-NH2 disappeared from serum with a half-life of approximately 1 h, and was recovered unchanged and quantitatively in urine. In contrast, when < EEP-NH2 was administered with food, only approximately 0.5% was recovered in urine. The urinary clearance rate of serum TRH-LI amounted to 0.52 +/- 0.10 ml/min in males and 0.34 +/- 0.05 ml/min in females. In view of the presence of < EEP-NH2 in the anterior pituitary gland, and the regulation of its content in parallel with gonadotrophins, we examined the possibility that serum < EEP-NH2 is of pituitary origin and correlates with gonadotrophin secretion. However, treatments that alter pituitary < EEP-NH2 content and gonadotrophin release had no effect on serum TRH-LI or urinary aTRH-LI. In conclusion, the TRH-like peptide < EEP-NH2 is present in rat serum and is excreted into the urine. Moreover, < EEP-NH2 in serum and urine is not derived from rat food and is probably not of pituitary origin.


Assuntos
Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/urina , Glândulas Suprarrenais/química , Animais , Química Encefálica , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Feminino , Meia-Vida , Hipotálamo/química , Masculino , Taxa de Depuração Metabólica , Ovário/química , Pâncreas/química , Hipófise/química , Próstata/química , Ácido Pirrolidonocarboxílico/análogos & derivados , Ratos , Ratos Wistar , Glândulas Salivares/química , Glândula Tireoide/química , Hormônio Liberador de Tireotropina/análise , Hormônio Liberador de Tireotropina/farmacocinética
4.
J Endocrinol ; 153(2): 259-67, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9166115

RESUMO

We investigated the effects of diabetes mellitus on the hypothalamo-hypophysial-thyroid axis in male (R x U) F1 and R-Amsterdam rats, which were found to respond to streptozotocin (STZ)-induced diabetes mellitus with no or marked increases, respectively, in plasma corticosterone. Males received STZ (65 mg/kg i.v.) or vehicle, and were killed 1, 2 or 3 weeks later. At all times studied, STZ-induced diabetes mellitus resulted in reduced plasma TSH, thyroxine (T4) and 3,5,3'-tri-iodothyronine (T3). Since the dialyzable T4 fraction increased after STZ, probably as a result of decreased T4-binding prealbumin, plasma free T4 was not altered during diabetes. In contrast, both free T3 and its dialyzable fraction decreased during diabetes, which was associated with an increase in T4-binding globulin. Hepatic activity of type I deiodinase decreased and T4 UDP-glucuronyltransferase increased after STZ treatment. Thus, the lowered plasma T3 during diabetes may be due to decreased hepatic T4 to T3 conversion. Median eminence content of TRH increased after STZ, suggesting that hypothalamic TRH release is reduced during diabetes and that this is not caused by impaired synthesis or axonal transport of TRH to the median eminence. Hypothalamic proTRH mRNA did not change in diabetic (R x U) F1 rats during the period of observation, but was lower in R-Amsterdam rats 3 weeks after STZ. Similarly, pituitary TSH and TSH beta mRNA had decreased in R-Amsterdam rats by 1 week after STZ treatment, but did not change in (R x U) F1 rats. The difference between the responses in diabetic R-Amsterdam and (R x U) F1 rats may be explained on the basis of plasma corticosterone levels which increased in R-Amsterdam rats only. Hypothalamic TRH content was not affected by diabetes mellitus, but the hypothalami of diabetic rats released less TRH in vitro than those of control rats. Moreover, insulin had a positive effect on TRH release in vitro. In conclusion, the reduced hypothalamic TRH release during diabetes is probably not caused by decreases in TRH synthesis or transport to the median eminence, but seems to be due to impaired TRH release from the median eminence which may be related to the lack of insulin. Inhibition of proTRH and TSH beta gene expression in diabetic R-Amsterdam rats is not a primary event but appears to be secondary to enhanced adrenal activity in these animals during diabetes.


Assuntos
Corticosterona/fisiologia , Diabetes Mellitus Experimental/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Animais , Corticosterona/sangue , Iodeto Peroxidase/metabolismo , Fígado/metabolismo , Masculino , Eminência Mediana/metabolismo , Técnicas de Cultura de Órgãos , Hipófise/metabolismo , Pró-Fármacos/metabolismo , Ratos , Ratos Wistar , Tireotropina/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo
5.
J Endocrinol ; 155(2): 393-9, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9415074

RESUMO

Recent studies have revealed that TRH-like immunoreactivity (TRH-LI) in human serum is predominantly pGlu-Glu-ProNH2 (< EEP-NH2), a peptide previously found in, among others tissues, the pituitary gland of various mammalian species. In the rat pituitary, < EEP-NH2 is present in gonadotrophs and its pituitary content is regulated by gonadal steroids and gonadotrophin-releasing hormone (GnRH). Hence, we reasoned that < EEP-NH2 in human serum may also arise, at least in part, from the pituitary, and that its secretion may correlate with that of gonadotrophins. Therefore, blood was simultaneously sampled from both inferior petrosal sinuses, which are major sites of the venous drainage of the pituitary gland, and a peripheral vein from seven patients with suspected adrenocorticotrophin-secreting pituitary tumours. In addition, in six postmenopausal and six cyclic women, peripheral vein blood was collected at 10-min intervals for 6 h, then a standard 100 micrograms GnRH test was performed. In the sera, TRH-LI was estimated by RIA with antiserum 4319, which binds most tripeptides that share the N- and C-terminal amino acids with TRH (pGlu-His-ProNH2). In addition, LH and FSH were measured in these sera by RIA. In the blood samples taken at 10-min intervals, an episodic variation in serum TRH-LI was noted and pulses of TRH-LI were detected at irregular intervals (from one to six pulses per 6 h) in five postmenopausal and six cyclic women. In general, these pulses did not coincide with those of LH and FSH, suggesting that TRH-LI is not co-secreted with gonadotrophins. Moreover, unlike LH and FSH, serum TRH-LI did not increase during the menopause or after exogenous administration of GnRH. Whereas gonadotrophin concentrations were significantly greater in the inferior petrosal sinus than in peripheral serum, there were no differences in TRH-LI concentrations between these serum samples. In conclusion, serum TRH-LI in humans seems not to be regulated by gonadal steroids or GnRH. Moreover, serum derived directly from the pituitary contained no more TRH-LI than did peripheral serum, which suggests that the human pituitary gland does not secrete significant amounts of < EEP-NH2, and therefore does not contribute significantly to serum TRH-LI concentrations. Further research is required to identify the site of origin of < EEP-NH2 in human serum.


Assuntos
Hipófise/metabolismo , Hormônio Liberador de Tireotropina/análogos & derivados , Adulto , Idoso , Cromatografia Líquida de Alta Pressão , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina , Humanos , Ensaio Imunorradiométrico , Hormônio Luteinizante/sangue , Masculino , Menstruação/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Amostragem do Seio Petroso , Neoplasias Hipofisárias/sangue , Pós-Menopausa/sangue , Ácido Pirrolidonocarboxílico/análogos & derivados , Radioimunoensaio , Hormônio Liberador de Tireotropina/sangue
6.
J Endocrinol ; 150(2): 169-78, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8869583

RESUMO

The reduced thyroid activity during short-term starvation is associated with a lowered hypothalamic synthesis and secretion of TRH. However, little is known about the cause of the reduced thyroid function during prolonged malnutrition. We have therefore studied the effects of food reduction to one-third of normal (FR33) on the hypothalamus-pituitary-thyroid axis of male and female Wistar rats. After 3 weeks body weights of FR33 rats were almost 50% lower than those of controls. In both sexes, FR33 caused marked increases in serum corticosterone, and decreases in serum TSH, thyroxine (T4), free T4, tri-iodothyronine (T3) and free T3. While the free T3 fraction (FFT3) in serum decreased, the free T4 fraction (FFT4) tended to increase. Electrophoretic analysis indicated that decreased FFT3 was correlated with an increased thyroxine-binding globulin, while the increase in FFT4 seemed due to a decreased thyroxine-binding prealbumin binding capacity. Total RNA and proTRH mRNA in the hypothalamus were not affected by FR33. Median eminence and posterior pituitary TRH content tended to increase in FR33 rats, suggesting that hypothalamic TRH release is reduced in FR33 rats. Anterior pituitary TSH content was decreased by FR33 in both sexes, but pituitary TSH beta mRNA and TRH receptor status were not affected except for increased pituitary TSH beta mRNA in female FR33 rats. Although FR33 had no effect on pituitary weight, pituitary RNA and membrane protein content in FR33 rats were 50-70% lower than values in controls. In conclusion, prolonged food reduction suppresses the pituitary-thyroid axis in rats. In contrast to short-term food deprivation, the mechanism whereby serum TSH is suppressed does not appear to involve decreases in proTRH gene expression, but may include effects on pituitary mRNA translation. Our results further support the hypothesis that TSH release may be lowered by increased corticosterone secretion, although the mechanism of this effect may differ between acute starvation and prolonged food reduction.


Assuntos
Privação de Alimentos/fisiologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Glândula Tireoide/fisiopatologia , Animais , Peso Corporal , Corticosterona/sangue , Feminino , Masculino , Hipófise/química , Hipófise/metabolismo , Precursores de Proteínas/genética , Ácido Pirrolidonocarboxílico/análogos & derivados , RNA Mensageiro/análise , Ratos , Ratos Wistar , Tireotropina/sangue , Hormônio Liberador de Tireotropina/genética , Hormônio Liberador de Tireotropina/metabolismo , Tiroxina/sangue , Tri-Iodotironina/sangue
7.
J Clin Endocrinol Metab ; 81(8): 2816-20, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8768836

RESUMO

The TRH-like peptide pGlu-Glu-Pro-NH2 ( < EEP-NH2) has been identified in the prostate, the anterior pituitary, and a human neuroblastoma cell line. We here report the determination of TRH-like immunoreactivity (TRH-LI) in serum of control subjects and patients with carcinoid tumors. TRH-LI was distinguished from authentic TRH (pGlu-His-Pro-NH2) in RIAs using the nonspecific antiserum 4319, which recognizes most peptides with the structure pGlu-X-Pro-NH2, or the TRH-specific antiserum 8880. TRH levels were undetectable ( < 25 pg/mL) in unextracted serum from healthy subjects, whereas the TRH-LI level was 42 +/- 22 pg/mL (mean +/- SD; n = 175). TRH levels were also undetectable in unextracted serum from 60 patients with carcinoid tumors, whereas TRH-LI levels ranged from less than 10 to 2540 pg/mL, being elevated in 27 of 60 (45%) patients. Serum TRH-LI was significantly correlated with 1) the number of tumor localizations (tumor load), 2) the presence of liver metastases, and 3) urinary 5-hydroxyindoleacetic acid excretion. Serum TRH-LI was completely extracted with methanol, and its identity was analyzed in serum extracts from 3 patients with carcinoid tumors by QAE-Sephadex A-25 anion exchange chromatography and reverse phase high performance liquid chromatography. With both techniques, TRH-LI predominantly coeluted with synthetic < EEP-NH2, suggesting secretion of this peptide by carcinoid tumors. The mechanism of < EEP-NH2 production by these tumors and its possible biological function remain to be determined.


Assuntos
Tumor Carcinoide/sangue , Hormônio Liberador de Tireotropina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Soros Imunes , Masculino , Pessoa de Meia-Idade , Ácido Pirrolidonocarboxílico/análogos & derivados , Radioimunoensaio , Valores de Referência , Hormônio Liberador de Tireotropina/sangue , Hormônio Liberador de Tireotropina/metabolismo
8.
J Endocrinol ; 148(2): 325-36, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8699147

RESUMO

This study describes the effects of litter size and acute suckling on the synthesis and release of hypothalamic TRH, as indirectly estimated by determination of hypothalamic prothyrotrophin-releasing hormone (proTRH) mRNA and median eminence TRH content. The effects of litter size (five or ten pups) were studied throughout lactation, while suckling-induced acute changes were analyzed on day 13 of lactation in dams with ten pups. In view of the enhanced adrenal activity during lactation and recent evidence that corticosteroids have negative effects on hypothalamic TRH, we also studied adrenalectomized (ADX) dams treated with corticosterone to maintain basal plasma corticosterone levels. In addition to an increased plasma level of prolactin (PRL), adrenal weight and plasma corticosterone increased, while plasma TSH, tri-iodothyronine (T3), thyroxine (T4) and free T4 (FT4) levels decreased during lactation. Litter size correlated positively with plasma PRL, adrenal weight and plasma corticosterone. No effect of litter size was observed on plasma T3, but rats with ten pups had lower plasma TSH, T4 and FT4 than rats with a five-pup litter. Compared with dioestrous rats, lactating rats showed an increased hypothalamic proTRH mRNA content on day 2, but not on days 8 and 15 of lactation. Median eminence TRH in lactating rats gradually increased until day 15 and decreased thereafter. Acute suckling, after a 6-h separation of mother and pups, rapidly increased plasma PRL and corticosterone in the mothers, but had no effects on plasma TSH and thyroid hormone levels. Hypothalamic proTRH mRNA increased twofold after 0.5 h of suckling, and then gradually returned to presuckling values after 6 h. Compared with sham-operated rats, corticosterone-substituted ADX rats with ten pups had increased plasma PRL and TSH, hypothalamic proTRH mRNA and pituitary TSH beta mRNA on day 15 of lactation. Moreover, while acute suckling did not enhance TSH release in sham-operated rats, it provoked not only PRL but also TSH release in corticosterone-substituted ADX dams. It is concluded that suckling exerts a rapid, positive effect on hypothalamic proTRH mRNA content. However, the concurrent enhanced adrenal activity has negative effects on hypothalamic proTRH gene expression resulting in a suppressed hypophysial-thyroid axis during lactation. While TRH appears to play a role in PRL release during the first days of lactation and during acute suckling, TRH seems not important in maintaining PRL secretion during continued suckling.


Assuntos
Corticosterona/fisiologia , Lactação/fisiologia , Prolactina/metabolismo , Hormônio Liberador de Tireotropina/fisiologia , Tireotropina/metabolismo , Adrenalectomia , Animais , Corticosterona/farmacologia , Feminino , Lactação/sangue , Tamanho da Ninhada de Vivíparos , Eminência Mediana/química , Prolactina/sangue , Precursores de Proteínas/genética , Ácido Pirrolidonocarboxílico/análogos & derivados , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos , Tireotropina/sangue , Hormônio Liberador de Tireotropina/análise , Hormônio Liberador de Tireotropina/genética
9.
J Endocrinol ; 146(2): 293-300, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7561642

RESUMO

Recent evidence shows that thyrotrophin-releasing hormone (TRH) immunoreactivity in the rat anterior pituitary gland is accounted for by the TRH-like tripeptide pyroglutamyl-glutamyl-prolineamide (pGlu-Glu-ProNH2, < EEP-NH2). The present study was undertaken to investigate further the regulation, localization and possible intrapituitary function of < EEP-NH2. Anterior pituitary levels of < EEP-NH2 were determined between days 5 and 35 of life, during the oestrous cycle and after treatment with the luteinizing hormone-releasing hormone (LHRH) antagonist Org 30276. Treatment of adult males with the LHRH antagonist either for 1 day (500 micrograms/100 g body weight) or for 5 days (50 micrograms/100 g body weight) reduced anterior pituitary < EEP-NH2 levels by 25-30% (P < 0.05 versus saline-treated controls). Anterior pituitary < EEP-NH2 increased between days 5 and 35 of life. In females, these levels were 2- to 3-fold higher (P < 0.05) than in males between days 15 and 25 after birth; these changes corresponded with the higher plasma follicle-stimulating hormone (FSH) levels in the female rats. After day 25, < EEP-NH2 levels in female rats decreased in parallel with a decrease in plasma FSH. Injections with the LHRH antagonist (500 micrograms/100 g body weight), starting on day 22 of life, led to reduced contents of < EEP-NH2 in the anterior pituitary gland of female rats on days 26 and 30 (55 and 35% decrease respectively). Levels of < EEP-NH2 in the anterior pituitary gland did not change significantly during the oestrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Adeno-Hipófise/metabolismo , Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/metabolismo , Animais , Animais Recém-Nascidos/metabolismo , Células Cultivadas , Estro/metabolismo , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/farmacologia , Masculino , Adeno-Hipófise/efeitos dos fármacos , Ácido Pirrolidonocarboxílico/análogos & derivados , Radioimunoensaio , Ratos , Ratos Wistar , Hormônio Liberador de Tireotropina/análise , Hormônio Liberador de Tireotropina/fisiologia
10.
Hybridoma ; 14(3): 285-90, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7590793

RESUMO

In this article, two mouse monoclonal antibodies (83-7B5-A1 and 83-6B6-A10) and three rabbit polyclonal antibodies (1118, 8572, and 8577) directed against thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2) are described. The anti-TRH antibodies were raised by immunization with a TRH-bovine serum albumin conjugate obtained by coupling of the CO2H group of pGlu-His-Pro-OH to NH2 groups in the protein. The monoclonal antibodies were produced by hybridoma clones obtained by the fusion of SP2/0 myeloma cells with spleen cells of an immunized BALB/c mouse. Both monoclonal antibodies were of the IgG1 (kappa) subclass. Characterization of the anti-TRH antibodies showed that in general they are specific for the pGlu-His moiety. The cross-reactivities for the TRH-like peptides [Glu1]TRH, [Glu2]TRH, and [Phe2]TRH are low, while alterations at the Pro-NH2 moiety of TRH are recognized to varying extents. The specificities of these antibodies are markedly different from those previously obtained using TRH coupled through the histidine residue to protein as the immunogen.


Assuntos
Anticorpos Monoclonais/biossíntese , Hormônio Liberador de Tireotropina/imunologia , Sequência de Aminoácidos , Animais , Anticorpos/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Coelhos , Hormônio Liberador de Tireotropina/química , Tiramina/imunologia
11.
Neuroendocrinology ; 61(4): 421-9, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7783855

RESUMO

Although the presence of thyrotropin-releasing hormone (TRH) in the posterior pituitary (PP) was reported more than one decade ago, knowledge on its origin, regulation and functional significance is lacking. In the present study we investigated the regulation of TRH in the rat PP. Analysis by specific RIA, anion and cation exchange chromatography and reverse-phase HPLC showed that all TRH immunoreactivity in the PP is accounted for by authentic TRH. Induction of hyperthyroidism with thyroxine increased levels of TRH in the PP by 20%, whereas in methimazole-treated, hypothyroid rats the content decreased by 25% versus untreated, euthyroid controls. Food deprivation for 3 days increased levels by 35% and refeeding completely normalized TRH content again. Also 14-17 days after castration, TRH in the PP was increased by 25% while testosterone substitution prevented this increase. Castration did not affect proTRH mRNA levels in the hypothalamus. One week after adrenalectomy or daily subcutaneous dexamethasone injections, TRH content in the PP was not affected. Treatment with disulfiram, an inhibitor of the peptidylglycine alpha-amidating monooxygenase (PAM), reduced levels of TRH in the PP by 20%. ProTRH and PAM mRNA levels were not affected in the hypothalamus by this treatment. Since TRH in the PP has been suggested to play a role in prolactin (PRL) release, we determined the content of TRH in the PP during a 6-hour suckling stimulus that increased PRL levels in peripheral blood 30-fold. Whereas TRH in the median eminence increased by 35%, 6 h after the initiation of suckling, TRH levels in the PP remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Neuro-Hipófise/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Adrenalectomia , Animais , Northern Blotting , Cromatografia , Dexametasona/farmacologia , Dissulfiram/farmacologia , Jejum , Feminino , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Lactação , Masculino , Eminência Mediana/metabolismo , Orquiectomia , Radioimunoensaio , Ratos , Ratos Endogâmicos
12.
J Endocrinol ; 145(1): 143-53, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7798020

RESUMO

The purpose of this study was to investigate the mechanisms involved in the reduced thyroid function in starved, young female rats. Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160-169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSH beta mRNA. Plasma TSH was either not affected or slightly reduced by starvation, but food deprivation induced marked increases in plasma corticosterone and decreases in plasma thyroid hormones. Refeeding after starvation normalized these parameters. Since the molar ratio of TRH and proTRH160-169 in hypophysial portal blood was not affected by food deprivation, it seems unlikely that proTRH processing is altered by starvation. The median eminence content of pGlu-His-Pro-Gly (TRH-Gly, a presumed immediate precursor of TRH), proTRH160-169 or TRH were not affected by food deprivation. Since median eminence TRH-Gly levels were very low compared with other proTRH-derived peptides it is unlikely that alpha-amidation is a rate-limiting step in hypothalamic TRH synthesis. Possible negative effects of the increased corticosterone levels during starvation on proTRH and TSH synthesis were studied in adrenalectomized rats which were treated with corticosterone in their drinking water (0.2 mg/ml). In this way, the starvation-induced increase in plasma corticosterone could be prevented. Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSH beta mRNA and plasma TSH in starved adrenalectomized rats. Thus, high levels of corticosteroids seem to exert negative effects on the synthesis and release of proTRH and TSH. This conclusion is corroborated by the observation that TRH release into hypophysial portal blood became reduced after administration of the synthetic glucocorticosteroid dexamethasone. On the basis of these results, it is suggested that the reduced thyroid function during starvation is due to a reduced synthesis and release of TRH and TSH. Furthermore, the reduced TRH and TSH synthesis during food deprivation are probably caused by the starvation-induced enhanced adrenal secretion of corticosterone.


Assuntos
Glândulas Suprarrenais/fisiologia , Hipotálamo/metabolismo , Precursores de Proteínas/genética , RNA Mensageiro/metabolismo , Inanição/metabolismo , Hormônio Liberador de Tireotropina/genética , Hormônio Liberador de Tireotropina/metabolismo , Adrenalectomia , Animais , Northern Blotting , Corticosterona/metabolismo , Dexametasona/farmacologia , Feminino , Hibridização In Situ , Fragmentos de Peptídeos/metabolismo , Ácido Pirrolidonocarboxílico/análogos & derivados , Radioimunoensaio , Ratos , Ratos Wistar , Tireotropina/sangue , Hormônio Liberador de Tireotropina/sangue , Fatores de Tempo
13.
J Endocrinol ; 145(1): 43-9, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7798029

RESUMO

TRH-like peptides share the N- and C-terminal amino acids with TRH (pGlu-His-Pro-NH2) but differ in the middle amino acid residue. One of them, pGlu-Glu-Pro-NH2 (< EEP-NH2; EEP) is present in the rat pituitary gland, but its biological significance is unknown. We investigated the localization and regulation of this tripeptide in the rat pituitary gland. To distinguish between TRH and EEP two antisera were used for RIA: specificity of antiserum 4319 for the TRH-like peptides pGlu-Phe-Pro-NH2 and EEP was equal to or greater than that for TRH, whereas antiserum 8880 is TRH-specific. Our RIA data showed the presence of a TRH-like peptide in the anterior pituitary gland (AP) and of TRH in the posterior pituitary gland (PP). The TRH-like peptide in the AP was identified on anion-exchange chromatography and subsequent HPLC as EEP. Pathophysiological conditions such as altered thyroid and adrenal status and suckling did not affect pituitary gland levels of EEP. In general, however, there is a clear sex difference: levels of EEP are higher in male than in female rats. In both sexes gonadectomy leads to a substantial two- to threefold rise in EEP levels, abolishing the sex difference. Testosterone administration to gonadectomized male rats normalizes levels of EEP again. Disulfiram, an inhibitor of the enzyme peptidylglycine alpha-amidating monooxygenase, reduced levels of EEP in the AP by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Adeno-Hipófise/metabolismo , Hormônio Liberador de Tireotropina/análogos & derivados , Adrenalectomia , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Dissulfiram/farmacologia , Feminino , Masculino , Orquiectomia , Ovariectomia , Adeno-Hipófise/efeitos dos fármacos , Neuro-Hipófise/química , Ácido Pirrolidonocarboxílico/análogos & derivados , Radioimunoensaio , Ratos , Ratos Wistar , Testosterona/farmacologia , Tireoidectomia , Hormônio Liberador de Tireotropina/análise , Hormônio Liberador de Tireotropina/metabolismo
14.
Brain Res ; 665(2): 262-8, 1994 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-7895062

RESUMO

The human neuroblastoma cell line IMR32 produces and secretes substantial amounts of TRH-immunoreactivity (TRH-IR) as measured with radioimmunoassay (RIA) using the nonspecific antiserum 4319. It was found that synthesis of TRH-IR is dependent on neural differentiation: under serum-free conditions these cells exhibit neural characteristics as defined by morphological and biochemical standards. After culture for 2-5 days in serum-free medium cells grew large neural processes and expressed neuron-specific markers whereas glial-specific markers were absent. TRH-IR became detectable after 4-8 days serum-free conditions. Northern blot and chromatographic analysis, however, failed to detect proTRH mRNA and authentic TRH in these cells. Moreover, TRH-IR was undetectable in the RIA using TRH-specific antiserum 8880. TRH-IR produced by differentiated cells was retained on a QAE Sephadex A-25 anion-exchange column and thus negatively charged. HPLC analysis showed coelution with the synthetic peptide pGlu-Glu-ProNH2. Study of the mechanisms regulating production of this novel peptide in these cells should further elucidate the role differentiation plays in the synthesis of neuropeptides.


Assuntos
Neuroblastoma/patologia , Neurônios/patologia , Hormônio Liberador de Tireotropina/metabolismo , Northern Blotting , Diferenciação Celular/fisiologia , Cromatografia Líquida de Alta Pressão , Humanos , Ácido Pirrolidonocarboxílico/análogos & derivados , Radioimunoensaio , Hormônio Liberador de Tireotropina/análogos & derivados , Fatores de Tempo , Células Tumorais Cultivadas
15.
Endocrinology ; 135(4): 1336-45, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7925094

RESUMO

The cytokines interleukin-1 (IL-1) and IL-6 are thought to be important mediators in the suppression of thyroid function during nonthyroidal illness. In this study we compared the effects of IL-1 and IL-6 infusion on the hypothalamus-pituitary-thyroid axis in rats. Cytokines were administered by continuous ip infusion of 4 micrograms IL-1 alpha/day for 1, 2, or 7 days or of 15 micrograms IL-6/day for 7 days. Body weight and temperature, food and water intake, and plasma TSH, T4, free T4 (FT4), T3, and corticosterone levels were measured daily, and hypothalamic pro-TRH messenger RNA (mRNA) and hypophysial TSH beta mRNA were determined after termination of the experiments. Compared with saline-treated controls, infusion of IL-1, but not of IL-6, produced a transient decrease in food and water intake, a transient increase in body temperature, and a prolonged decrease in body weight. Both cytokines caused transient decreases in plasma TSH and T4, which were greater and more prolonged with IL-1 than with IL-6, whereas they effected similar transient increases in the plasma FT4 fraction. Infusion with IL-1, but not IL-6, also induced transient decreases in plasma FT4 and T3 and a transient increase in plasma corticosterone. Hypothalamic pro-TRH mRNA was significantly decreased (-73%) after 7 days, but not after 1 or 2 days, of IL-1 infusion and was unaffected by IL-6 infusion. Hypophysial TSH beta mRNA was significantly decreased after 2 (-62%) and 7 (-62%) days, but not after 1 day, of IL-1 infusion and was unaffected by IL-6 infusion. These results are in agreement with previous findings that IL-1, more so than IL-6, directly inhibits thyroid hormone production. They also indicate that IL-1 and IL-6 both decrease plasma T4 binding. Furthermore, both cytokines induce an acute and dramatic decrease in plasma TSH before (IL-1) or even without (IL-6) a decrease in hypothalamic pro-TRH mRNA or hypophysial TSH beta mRNA, suggesting that the acute decrease in TSH secretion is not caused by decreased pro-TRH and TSH beta gene expression. The TSH-suppressive effect of IL-6, either administered as such or induced by IL-1 infusion, may be due to a direct effect on the thyrotroph, whereas additional effects of IL-1 may involve changes in the hypothalamic release of somatostatin or TRH.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Interleucina-1/farmacologia , Interleucina-6/farmacologia , Glândula Tireoide/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Corticosterona/metabolismo , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Expressão Gênica , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Hipotálamo/química , Masculino , Eminência Mediana/química , Hipófise/química , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Precursores de Proteínas/genética , Ácido Pirrolidonocarboxílico/análogos & derivados , RNA Mensageiro/análise , RNA Mensageiro/genética , Radioimunoensaio , Ratos , Ratos Wistar , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tireotropina/genética , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/análise , Hormônio Liberador de Tireotropina/sangue , Hormônio Liberador de Tireotropina/genética , Tiroxina/sangue , Tiroxina/metabolismo , Tri-Iodotironina/sangue , Tri-Iodotironina/metabolismo
16.
Neuroendocrinology ; 56(3): 348-53, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1436373

RESUMO

Effects of starvation on thyroid function were studied in 5- to 6-week-old (R x U) F1 rats. Starvation lowered plasma TSH in female, but not in male rats. Plasma T4 and T3 levels decreased, whereas the dialysable T4 fraction increased during starvation. Free T4 (FT4) levels decreased rapidly in females, but only after prolonged fasting in male rats. Glucose decreased, and free fatty acid levels increased during starvation. Peripheral TRH levels did not change during food deprivation. Since effects of starvation were most apparent in young female rats, such rats were used to study hypothalamic TRH release during starvation and subsequent refeeding. Basal in vitro hypothalamic TRH secretion was less in starved rats than in control or refed animals. In vitro hypothalamic TRH release in medium with 56 mM KCl increased 3-fold compared to basal release, and in these depolarization conditions TRH release was similar between hypothalami from control, starved and refed rats. In rats starved for 2 days, TRH level in hypophysial portal blood was lower than that of controls. Thus, diminished thyroid function during starvation may at least in part be caused by a reduced hypothalamic TRH release.


Assuntos
Ingestão de Alimentos/fisiologia , Hipotálamo/metabolismo , Inanição/fisiopatologia , Glândula Tireoide/fisiopatologia , Hormônio Liberador de Tireotropina/metabolismo , Animais , Feminino , Masculino , Hipófise/irrigação sanguínea , Veia Porta , Ratos , Ratos Wistar , Caracteres Sexuais , Hormônio Liberador de Tireotropina/sangue
17.
Acta Endocrinol (Copenh) ; 126(3): 276-81, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1574958

RESUMO

The significance of TRH for pituitary function is still unresolved mainly due to limitations in determining in vivo hypothalamic TRH release. We therefore examined whether TRH immunoreactivity (TRH-IR) in peripheral blood is an index for hypothalamic TRH release. Peripheral TRH-IR varied between 10 and 55 pmol/l and was similar in euthyroid and hypothyroid rats, but lower in hyperthyroid rats. Destruction of the hypothalamic paraventricular area reduced peripheral TRH-IR, while stimulation of this area increased it. Clearance of TRH during continuous TRH infusion was 1.9 +/- 0.2, 3.5 +/- 0.3 and 5.9 +/- 0.8 ml/min in hypothyroid, euthyroid and hyperthyroid rats, respectively. These and previous data on TRH in hypophysial portal blood indicate that 5-25 pmol TRH/l peripheral blood is of hypothalamic origin. Chromatography revealed that TRH-IR from hypothalamus and portal blood co-eluted with TRH, but in peripheral blood two peaks were found, one of which was authentic TRH. Thus, peripheral TRH-IR alters in experimental conditions and part of it seems to be of hypothalamic origin. However, the presence of TRH-like material in peripheral blood not identical to TRH and the fact that experimental conditions alter TRH clearance indicate that peripheral TRH-IR is not an index for hypothalamic TRH release.


Assuntos
Hipotálamo/metabolismo , Hormônio Liberador de Tireotropina/sangue , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Radioimunoensaio , Ratos , Ratos Endogâmicos , Hormônio Liberador de Tireotropina/metabolismo
18.
Endocrinology ; 130(2): 651-6, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1733713

RESUMO

The aim of this study was to investigate whether the severity and duration of primary hypothyroidism influence hypothalamic TRH release. Hypothyroidism was induced in male Wistar rats by treatment with different thyrostatic drugs or by thyroidectomy. Serum TSH in rats treated for up to 3 weeks with methimazole (MMI; 0.05% in drinking water) increased 20-fold, but TRH release into hypophyseal portal blood (HPB) did not change. Treatment with propylthiouracil (PTU; 0.1% in drinking water), which inhibits thyroidal T4 production and peripheral conversion of T4 to T3, resulted in a more rapid reduction in serum T3 levels and increase in serum TSH than those in rats treated with 0.1% MMI. Although these differences were no longer observed after 3 weeks of treatment, TRH release into HPB of rats treated with PTU was 34-49% higher than that in MMI-treated rats. Combined treatment with MMI (0.05-0.1% in drinking water) and iopanoic acid (IOP; 4 mg/100 g BW.day, ip), an inhibitor of both peripheral and central T4 to T3 conversion, also tended to produce a more rapid decrease in serum T3 and increase in serum TSH. After 3 weeks of treatment, serum T4, T3, and TSH were not different in the two groups, but TRH release into HPB was 48-65% increased by MMI plus IOP vs. MMI alone. Three to 10 weeks after thyroidectomy, TRH release into HPB was 58-72% higher than that in untreated controls. In vitro incubation of hypothalami isolated from rats treated for 3 weeks with MMI, MMI plus IOP, or PTU, as described above, showed that basal and 56 mM K(+)-induced TRH release were not influenced by the different drugs. Also, the total hypothalamic TRH content was not changed by any of these treatments. However, in rats treated for 1 or 2 weeks with MMI or PTU, the TRH content of the median eminence was decreased by 17-25%. These findings indicate that, depending on severity and duration, experimental hypothyroidism may cause a significant increase in hypothalamic TRH release in rats. The magnitude of these changes compared with the much larger increases in serum TSH suggests that the feedback of thyroid hormone on TSH secretion is mainly exerted at the pituitary level.


Assuntos
Hipotálamo/metabolismo , Hipotireoidismo/fisiopatologia , Ácido Iopanoico/farmacologia , Eminência Mediana/metabolismo , Metimazol/farmacologia , Propiltiouracila/farmacologia , Hormônio Liberador de Tireotropina/metabolismo , Tireotropina/metabolismo , Animais , Hipotálamo/efeitos dos fármacos , Hipotireoidismo/induzido quimicamente , Técnicas In Vitro , Masculino , Eminência Mediana/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Valores de Referência , Tireoidectomia , Tireotropina/sangue , Tri-Iodotironina/sangue
19.
Acta Med Austriaca ; 19 Suppl 1: 77-9, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1519460

RESUMO

Thyrotropin-releasing hormone (TRH) is produced in the hypothalamic paraventricular nucleus (PVN) as a 255-amino acid precursor (pro-TRH) with 5 TRH progenitor sequences. Pro-TRH is enzymatically processed to yield TRH and other peptides, which are transported to the median eminence and released into hypophysial portal blood. To elucidate the role of TRH in the control of thyroid function, we studied hypothalamic TRH synthesis and release in many conditions. TRH synthesis and release were assessed by pro-TRH mRNA measurement, and by sampling portal blood or push-pull perfusate, respectively. Destruction of the PVN reduced TRH and TSH secretion dramatically, while electrical stimulation of this nucleus enhanced their release. Hence, the PVN is important for normal TSH secretion. TRH synthesis and release decreased in hyperthyroid rats, but increased in hypothyroid rats. The magnitude of these changes, however, was small compared with alterations in TSH, suggesting that the feedback of thyroid hormones on TSH release is mainly exerted at the pituitary level. TRH synthesis and release increased during cold exposure, and decreased during starvation and diabetes. Thus, altered thyroid function during cold exposure, diabetes and starvation seems due to modified hypothalamic TRH synthesis and release.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Glândula Tireoide/fisiologia , Hormônio Liberador de Tireotropina/sangue , Animais , Precursores de Proteínas/sangue , Ácido Pirrolidonocarboxílico/análogos & derivados , Ratos
20.
Endocrinology ; 123(1): 523-7, 1988 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3133200

RESUMO

TRH is a potent stimulator of pituitary TSH release, but its function in the physiological regulation of thyroid activity is still controversial. The purpose of the present study was to investigate TRH and catecholamine secretion into hypophysial portal blood of hypothyroid and hyperthyroid rats, and in rats bearing paraventricular area lesions. Male rats were made hypothyroid with methimazole (0.05% in drinking water) or hyperthyroid by daily injections with T4 (10 micrograms/100 g BW). Untreated male rats served as euthyroid controls. On day 8 of treatment they were anesthetized to collect peripheral and hypophysial stalk blood. In euthyroid, hypothyroid and hyperthyroid rats plasma T3 was 1.21 +/- 0.04, 0.60 +/- 0.04, and 7.54 +/- 0.33 nmol/liter, plasma T4 50 +/- 3, 16 +/- 2, and 609 +/- 74 nmol/liter, and plasma TSH 1.58 +/- 0.29, 8.79 +/- 1.30, and 0.44 +/- 0.03 ng RP-2/ml, respectively. Compared with controls, hyperthyroidism reduced hypothalamic TRH release (0.8 +/- 0.1 vs. 1.5 +/- 0.2 ng/h) but was without effect on catecholamine release. Hypothyroidism did not alter TRH release, but the release of dopamine increased 2-fold and that of noradrenaline decreased by 20%. Hypothalamic TRH content was not affected by the thyroid status, but dopamine content in the hypothalamus decreased by 25% in hypothyroid rats. Twelve days after placement of bilateral electrolytic lesions in the paraventricular area plasma thyroid hormones and TSH levels were lower than in control rats (T3: 0.82 +/- 0.05 vs. 1.49 +/- 0.07 nmol/liter; T4: 32 +/- 4 vs. 66 +/- 3 nmol/liter; TSH: 1.08 +/- 0.17 vs. 3.31 +/- 0.82 ng/ml). TRH release in stalk blood in rats with lesions was 15% of that of controls, whereas dopamine and adrenaline release had increased by 50% and 40%, respectively. These results suggest that part of the feedback action of thyroid hormones is exerted at the level of the hypothalamus. Furthermore, TRH seems an important drive for normal TSH secretion by the anterior pituitary gland, and thyroid hormones seem to affect the hypothalamic release of catecholamines.


Assuntos
Dopamina/metabolismo , Epinefrina/metabolismo , Hipertireoidismo/sangue , Hipotireoidismo/sangue , Norepinefrina/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiologia , Glândula Tireoide/fisiologia , Hormônio Liberador de Tireotropina/metabolismo , Animais , Dopamina/sangue , Epinefrina/sangue , Masculino , Norepinefrina/sangue , Hipófise/irrigação sanguínea , Ratos , Ratos Endogâmicos , Valores de Referência , Hormônio Liberador de Tireotropina/sangue
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