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1.
Chemosphere ; 241: 125118, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31683416

RESUMO

Deltamethrin (DM) has become one of the most widely used insecticides in the world due to its low toxicity, high efficiency and low persistence in soil. However, it is still unknown whether DM exposure has any effects on the Hypothalamic-Pituitary-Thyroid (HPT) axis in adolescent mice. In this study, the open field test and circadian activity test showed that DM exposure increased activity. There was no significant difference between the groups in the light/dark box test and nest building test. Forced swimming test showed that after 6 and 12 mg kg-1 DM exposure 28 days, the immobility time was increased and the swimming time was reduced. After 6 mg kg-1 DM treatment, the thyroid stimulating hormone (TSH) content increased, and thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4) decreased. After exposure to 6 and 12 mg kg-1 DM, mRNA levels of HPT axis-related genes were destroyed. The histological examination showed that, the DM groups mice thyroid tissues appeared expanded thyroid follicles, scanty colloid and hyperplastic thyroid cells. Western blot results showed that the expression level of tyrosine hydroxylase (TH) protein decreased and the content of dopamine transporter (DAT) protein increased in DM treated mice striatum. Collectively, our results indicated that DM exposure could induce thyroid dysfunction and behavioral disorders in adolescent mice.


Assuntos
Transtornos Mentais/induzido quimicamente , Nitrilos/farmacologia , Piretrinas/farmacologia , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/metabolismo , Envelhecimento , Animais , Comportamento Animal/efeitos dos fármacos , Inseticidas/farmacologia , Masculino , Camundongos , Glândula Tireoide/metabolismo , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo
2.
J Vet Intern Med ; 33(5): 2249-2256, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31498947

RESUMO

BACKGROUND: The thyrotropin-releasing hormone (TRH) stimulation test and the 2-step insulin sensitivity test are commonly used methods to diagnose, respectively, pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID). OBJECTIVES: To investigate the diagnostic value of combining the TRH stimulation test and the 2-step insulin sensitivity test to diagnose PPID and ID simultaneously. ANIMALS: Twenty-seven adult horses, 10 control horses without PPID or ID, 5 horses with PPID only, 5 horses with ID only, and 7 horses with PPID and ID. METHODS: Randomized prospective study. Horses underwent a TRH stimulation test alone, a 2-step insulin sensitivity test alone, and combined testing with simultaneous TRH and insulin injection in the same syringe. Data were compared by 2-way repeated measures analysis of variance and 2 1-sided tests to demonstrate equivalence. Bland-Altman plots were generated to visualize agreement between combined and independent testing. RESULTS: The effect of combined testing on plasma adrenocorticotropic hormone, blood glucose concentration, or percentage decrease in blood glucose concentration was not significantly different from the effect obtained with independent testing. One control horse appeared falsely positive for PPID, 2 PPID-only horses appeared falsely positive for ID, and 1 PPID and ID horse appeared falsely negative for ID when tests were performed simultaneously. Bland-Altman plots supported the agreement between combined and independent testing. CONCLUSIONS AND CLINICAL IMPORTANCE: Combining the TRH stimulation test and the 2-step insulin sensitivity test appears to be a useful diagnostic tool for equine practitioners in the field, allowing testing of a horse for both PPID and ID simultaneously.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Doenças dos Cavalos/diagnóstico , Resistência à Insulina , Doenças da Hipófise/veterinária , Animais , Glicemia , Feminino , Doenças dos Cavalos/sangue , Doenças dos Cavalos/metabolismo , Cavalos , Masculino , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico , Adeno-Hipófise Parte Intermédia/patologia , Estudos Prospectivos , Distribuição Aleatória , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/farmacologia
3.
J Vet Intern Med ; 33(5): 2272-2279, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31432575

RESUMO

BACKGROUND: The use of parallel dynamic tests to identify insulin dysregulation (ID) and pituitary pars intermedia dysfunction (PPID) in horses could have better diagnostic utility than measuring baseline hormone concentrations, if the tests do not alter diagnostic interpretation of one another. HYPOTHESIS: Performing a thyrotropin-releasing hormone (TRH) stimulation test before an oral sugar test (OST) would not affect results of OST. ANIMALS: Twenty-six healthy university-owned horses. METHODS: A prospective randomized placebo-controlled, crossover design was used to evaluate 3 OST protocols: OST alone, TRH followed by OST (TRH + OST), and placebo followed by OST (placebo + OST). Agreement for plasma insulin concentrations and diagnostic interpretation were assessed with Bland-Altman and logistic regression analyses, respectively. RESULTS: Bland-Altman analysis of TRH + OST versus OST alone showed good agreement between testing protocols, with bias ± SD for insulin concentrations at baseline 0.4 ± 4.7 µIU/mL (95% limits of agreement [LOA], -8.8 to 9.7), 60 minute -0.5 ± 22.6 µIU/mL (95% LOA, -44.7 to 43.8), and 90 minute 1.9 ± 20.6 µIU/mL (95% LOA, -38.5 to 42.4) after OST, similar to placebo + OST versus OST alone. Diagnostic interpretation (positive/negative) was not different between protocols (TRH + OST versus OST alone [P = .78], placebo + OST versus OST alone [P = .77], or TRH + OST versus placebo + OST [P = .57]). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent testing for PPID and ID with a TRH stimulation test before an OST is an acceptable diagnostic tool for investigation of endocrinopathies in horses and allows accurate testing to be performed efficiently in 1 visit.


Assuntos
Teste de Tolerância a Glucose/veterinária , Cavalos/sangue , Insulina/sangue , Hormônio Liberador de Tireotropina/farmacologia , Hormônio Adrenocorticotrópico/sangue , Animais , Estudos Cross-Over , Feminino , Cavalos/metabolismo , Masculino , Adeno-Hipófise Parte Intermédia/fisiologia , Estudos Prospectivos , Distribuição Aleatória
4.
Domest Anim Endocrinol ; 68: 135-141, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31082785

RESUMO

Published information on the pharmacokinetic and pharmacodynamic properties of pergolide is limited. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of oral pergolide in horses with pituitary pars intermedia dysfunction (PPID). The study design was a nonrandomized clinical trial. Six horses with PPID diagnosed by thyrotropin-releasing hormone (TRH) stimulation tests received pergolide at 4 µg/kg for 18 d. Plasma samples for determination of pergolide and ACTH concentration were collected 0.5 h before and 2 and 12 h after each administration of pergolide. Maximum plasma concentrations after the first oral dose of pergolide (0.104-0.684 ng/mL; median 0.261 ng/mL; interquartile range [IQR] 0.184-0.416 ng/mL) were not significantly different to the maximum steady-state concentration at day 18 (0.197-0.628 ng/mL; median 0.274; IQR 0.232-0.458 ng/mL). Chronic administration was not associated with drug accumulation (R = 1.09) and pergolide concentration reached steady state within 3 d. Throughout, concentrations of pergolide fluctuated considerably, with median plasma peak concentrations more than four times higher than median trough concentrations. Plasma ACTH concentration reduced significantly within 12 h of administration with further reductions occurring up to 10 d after the initiation of treatment. Although there were parallel fluctuations in the concentrations of pergolide and ACTH, timing of ACTH measurement in relation to the administration of pergolide did not have a significant effect. Alterations in the response to TRH were identified at 8 d with no further change being identified at 18 d. A small number of horses were studied. Oral pergolide results in significant suppression of pars intermedia activity within hours. Pergolide and ACTH concentrations fluctuated in tandem although correlation was poor. Fluctuations in pergolide concentration were consistent with a terminal elimination half-life of less than 12 h. To reduce the level of fluctuation of ACTH, twice-daily dosing of pergolide may be more appropriate.


Assuntos
Doenças dos Cavalos/tratamento farmacológico , Pergolida/farmacocinética , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/efeitos dos fármacos , Administração Oral , Hormônio Adrenocorticotrópico/sangue , Animais , Área Sob a Curva , Cavalos , Pergolida/administração & dosagem , Pergolida/sangue , Pergolida/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/farmacologia
5.
Int J Vitam Nutr Res ; 89(1-2): 80-88, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30982439

RESUMO

Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.


Assuntos
Glândula Tireoide/fisiologia , Hormônios Tireóideos/metabolismo , Hormônio Liberador de Tireotropina/fisiologia , Tireotropina , Zinco , Hormônios Tireóideos/química , Hormônio Liberador de Tireotropina/química
6.
Chem Commun (Camb) ; 55(35): 5159-5162, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30984931

RESUMO

We have reported a versatile nanopore method based on the combination of analyte-controlled liposome signal amplification and the nanopore detection of a reporter molecule, which largely extends the nanopore application range, and easily elevates the nanopore sensitivity to the fM level from the µM level.


Assuntos
Avidina/análise , Proteínas Hemolisinas/química , Nanoporos , Hormônio Liberador de Tireotropina/análise , Lipossomas Unilamelares/química , Biotina/química , Fosfatidilcolinas/química , Ácido Fítico/química
8.
Neurosci Lett ; 703: 79-85, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-30902570

RESUMO

Thyrotropin-releasing hormone (TRH) plays an important role in the regulation of energy balance. While the regulation of TRH in the paraventricular nucleus (PVN) in response to changes of energy balance has been well studied, how TRH is regulated in the dorsomedial hypothalamus (DMH) in maintaining energy homeostasis remains unclear. Here, we assessed the effects of food restriction and exercise on hypothalamic Trh expression using Otsuka Long-Evens Tokushima Fatty (OLETF) rats. Sedentary ad lib fed OLETF rats (OLETF-SED) became hyperphagic and obese. These alterations were prevented in OLETF rats with running wheel access (OLETF-RW) or food restriction in which their food was pair-fed (OLETF-PF) to the intake of lean control rats (LETO-SED). Evaluation of hypothalamic gene expression revealed that Trh mRNA expression was increased in the PVN of OLETF-SED rats and normalized in OLETF-RW and OLETF-PF rats compared to LETO-SED rats. In contrast, the expression of Trh in the DMH was decreased in OLETF-SED rats relative to LETO-SED rats. This alteration was reversed in OLETF-RW rats as seen in LETO-SED rats, but food restriction resulted in a significant increase in DMH Trh expression in OLETF-PF rats compared to LETO-SED rats. Strikingly, while Trh mRNA expression was decreased in the PVN of intact rats in response to acute food deprivation, food deprivation resulted in increased expression of Trh in the DMH. Together, these results demonstrate the differential regulation of Trh expression in the PVN and DMH in OLETF rats and suggest that DMH TRH also contributes to hypothalamic regulation of energy balance.


Assuntos
Núcleo Hipotalâmico Dorsomedial/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , RNA Mensageiro/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Animais , Glicemia , Peso Corporal , Dieta Redutora , Ingestão de Alimentos , Leptina/sangue , Masculino , Obesidade/fisiopatologia , Obesidade/psicologia , Condicionamento Físico Animal , Ratos , Hormônio Liberador de Tireotropina/genética
9.
Ecotoxicol Environ Saf ; 174: 224-235, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30844666

RESUMO

In recent years, decabromodiphenyl ethane (DBDPE), a new alternative flame retardant to the decabrominated diphenyl ethers (BDE-209), is widely used in a variety of products. Previous studies have indicated that DBDPE, like BDE-209, could disrupt thyroid function. However, compared with BDE-209, the degrees of thyrotoxicosis induced by DBDPE were not clear. In addition, the mechanism of thyrotoxicosis induced by DBDPE or BDE-209 was still under further investigation. In this study, male rats as a model were orally exposed to DBDPE or BDE-209 by 5, 50, 500 mg/kg bw/day for 28 days. Then, we assessed the thyrotoxicosis of DBDPE versus BDE-209 and explored the mechanisms of DBDPE and BDE-209-induced thyrotoxicosis. Results showed that decreased free triiodothyronine (FT3) and increased thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) in serum were observed in both 500 mg/kg bw/day BDE-209 and DBDPE group. Decreased total thyroxine (TT4), total T3 (TT3), and free T4 (FT4) were only observed in BDE-209 group but not in DBDPE group. Histological examination and transmission electron microscope examination showed that high level exposure to BDE-209 and DBDPE both caused significant changes in histological structure and ultrastructure of the thyroid gland. Additionally, oxidative damages of thyroid gland (decreased SOD and GSH activities, and increased MDA content) were also observed in both BDE-209 and DBDPE groups. TG contents in the thyroid gland was reduced in BDE-209 group but not in DBDPE group. Both BDE-209 and DBDPE affected the expression of hypothalamic-pituitary-thyroid (HPT) axis related genes. These findings suggested that both BDE-209 and DBDPE exposure could disrupt thyroid function in the direction of hypothyroidism and the underlying mechanism was likely to be oxidative stress and perturbations of HPT axis. However, DBDPE was found to be less toxic than BDE-209.


Assuntos
Bromobenzenos/toxicidade , Disruptores Endócrinos/toxicidade , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Glândula Tireoide/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Hipotálamo/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Ratos , Ratos Sprague-Dawley , Glândula Tireoide/metabolismo , Glândula Tireoide/ultraestrutura , Tireotropina/sangue , Hormônio Liberador de Tireotropina/sangue , Tri-Iodotironina/sangue
10.
J Stroke Cerebrovasc Dis ; 28(4): 988-993, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30660483

RESUMO

OBJECTIVE: The efficacy of thyrotropin-releasing hormone tartrate (TRH-T) for treating prolonged disturbance of consciousness due to aneurysmal subarachnoid hemorrhage (SAH) remains unclear. The purpose of the present study was to determine whether TRH-T was really effective, and what was the recovery factor when it was valid. This was a retrospective study of a single facility. METHODS: We treated 208 patients with aneurysmal SAH at our hospital between 2011 and 2017. Among them, we investigated 97 cases in which TRH-T was administered to prolonged disturbance of consciousness. Thirty one patients with Hasegawa dementia rating scale-revised (HDS-R) score less than 20 were included. Patients' HDS-R scores were evaluated 7 days after clipping the aneurysm and 2 days after completing a course of TRH-T treatment. HDS-R score increases of greater than or over equal to 8 and less than 8 were defined as good and poor outcomes, respectively. Outcomes were compared to 11 patients who did not receive TRH-T treatment. RESULTS: Average initial and post-treatment HDS-R scores were 9 ± 6.6 and 19 ± 9.5, respectively. The good outcome group included 19 patients. Statistically significant differences in HDS-R score changes were observed between the group with initial HDS-R scores of 0-4 and the other groups. Poor outcomes were significantly correlated with age of greater than 60 years and initial HDS-R scores less than oroverequal to 4 points. The improvement in HDS-R score was significantly greater in the TRH-T administration group than the control group. CONCLUSIONS: TRH-T was effective for treating prolonged disturbance of consciousness due to aneurysmal SAH, especially in young patients with HDS-R scores between 5 and 20.


Assuntos
Transtornos da Consciência/tratamento farmacológico , Estado de Consciência/efeitos dos fármacos , Hemorragia Subaracnóidea/tratamento farmacológico , Hormônio Liberador de Tireotropina/uso terapêutico , Adulto , Idoso , Transtornos da Consciência/diagnóstico , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/fisiopatologia , Hormônio Liberador de Tireotropina/análogos & derivados , Fatores de Tempo , Resultado do Tratamento
11.
Front Neuroendocrinol ; 52: 29-43, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29935915

RESUMO

Thyrotropin-releasing hormone (TRH) causes a variety of thyroidal and non-thyroidal effects, the best known being the feedback regulation of thyroid hormone levels. This was employed in the TRH stimulation test, which is currently little used. The role of TRH as a cancer biomarker is minor, but exaggerated responses to TSH and prolactin levels in breast cancer led to the hypothesis of a potential role for TRH in the pathogenesis of this disease. TRH is a rapidly degraded peptide with multiple targets, limiting its suitability as a biomarker and drug candidate. Although some studies reported efficacy in neural diseases (depression, spinal cord injury, amyotrophic lateral sclerosis, etc.), therapeutic use of TRH is presently restricted to spinocerebellar degenerative disease. Regulation of TRH production in the hypothalamus, patterns of expression of TRH and its receptor in the body, its role in energy metabolism and in prolactin secretion are addressed in this review.


Assuntos
Neoplasias da Mama/metabolismo , Hipotálamo/metabolismo , Hipófise/metabolismo , Prolactina/metabolismo , Degenerações Espinocerebelares/tratamento farmacológico , Doenças da Glândula Tireoide/metabolismo , Glândula Tireoide/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/uso terapêutico , Animais , Humanos , Doenças da Glândula Tireoide/diagnóstico
12.
Xenobiotica ; 49(1): 106-119, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29300135

RESUMO

1. The non-clinical pharmacokinetic profiles of rovatirelin, a novel thyrotropin-releasing hormone (TRH) analogue, were investigated in vivo and in vitro. 2. Rovatirelin orally administered to rats and dogs was rapidly absorbed and bioavailability was estimated to be 7.3 and 41.3%, respectively. The extent of plasma protein binding of rovatirelin in rats, dogs, and humans was low in all species (∼15%). The permeability of rovatirelin from blood to brain (permeability-surface area) ranged from 1.04 ± 0.14 to 1.29 ± 0.28 µL/min/g in rats, and rovatirelin was stable in rat plasma and brain homogenates. 3. The metabolite pattern was qualitatively similar in vitro and in vivo. In animals, rovatirelin aminopentanoic acid (rovatirelin-acid), rovatirelin aminopentanone (rovatirelin-ketone), rovatirelin pyrrolidine (4S)-hydroxy (rovatirelin-OH), (thiazoylalanyl)methylpyrrolidine (TAMP), 3-(4-thiazoyl)-l-alanine (TA), and unknown metabolites were observed. In human hepatocytes, TAMP was mainly formed and no unique human metabolite was observed. 4. The radioactivity from administered [14C]rovatirelin was predominantly excreted in faeces in rats and dogs, and almost all radioactivity was recovered 168 h after administration. Absorption, brain penetration, and stability of rovatirelin in the brain were greater than for taltirelin. 5. Thus, orally administered rovatirelin is a potentially improved treatment for spinocerebellar degeneration compared with taltirelin.


Assuntos
Oxazolidinonas/farmacocinética , Pirrolidinas/farmacocinética , Hormônio Liberador de Tireotropina/metabolismo , Animais , Cães , Humanos , Ratos
13.
Endocrine ; 63(1): 101-111, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30255291

RESUMO

Hypothalamic kisspeptin is a known principal activator of gonadotropin-releasing hormone neurons and governs the hypothalamic-pituitary-gonadal axis. Previous reports have shown that kisspeptin is also released into the hypophyseal portal circulation and directly affects the anterior pituitary. In this study, we examined the direct effect of kisspeptin on pituitary prolactin-producing cells. The rat pituitary somatolactotroph cell line GH3 expresses the kisspeptin receptor (Kiss1R); however, in these cells, kisspeptin failed to stimulate prolactin-promoter activity. When GH3 cells overexpressed Kiss1R, kisspeptin clearly increased prolactin-promoter activity, with a concomitant increase in extracellular signal-regulated kinase (ERK) and cAMP/protein kinase A (PKA) signaling pathways. In the experiments using GH3 cells overexpressing Kiss1R, kisspeptin did not potentiate thyrotropin-releasing hormone (TRH)-induced prolactin-promoter activity, but it potentiated the pituitary adenylate cyclase-activating polypeptide-induced prolactin-promoter activity, with a concomitant enhancement of ERK and PKA signaling pathways. Although the basal and TRH-induced prolactin-promoter activities were not modulated by increasing amounts of Kiss1R expression in GH3 cells, kisspeptin-stimulated prolactin-promoter activity was increased by the amount of Kiss1R overexpression. Endogenous Kiss1r mRNA expression in GH3 cells was significantly increased by treatment with estradiol (E2) but not by TRH. In addition, kisspeptin's ability to stimulate prolactin-promoter activity was restored after E2 treatment in non-transfected GH3 cells. Our current observations suggest that kisspeptin might have a direct effect on prolactin expression in the anterior pituitary prolactin-producing cells under the influence of E2, which may regulate Kiss1R expression and function.


Assuntos
Regulação da Expressão Gênica/genética , Kisspeptinas/genética , Prolactina/biossíntese , Prolactina/genética , Receptores de Kisspeptina-1/genética , Animais , Linhagem Celular , Proteínas Quinases Dependentes de AMP Cíclico/genética , Estradiol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Hipófise/metabolismo , Regiões Promotoras Genéticas/genética , Ratos , Transdução de Sinais/genética , Hormônio Liberador de Tireotropina/genética , Hormônio Liberador de Tireotropina/metabolismo
14.
Equine Vet J ; 51(4): 481-488, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30362589

RESUMO

BACKGROUND: Endocrine disorders are common in donkeys. Pituitary pars intermedia dysfunction (PPID) is thought to be a frequent disturbance in donkeys due to their longevity. However, information on PPID dynamic testing in donkeys is lacking. OBJECTIVES: The objective of this study was to evaluate the previously described guidelines for PPID diagnosis in horses in donkeys with suspicion of PPID. STUDY DESIGN: Prospective experimental study. METHODS: Eighty donkeys were evaluated for PPID suspicion based on clinical signs and baseline adrenocorticotropic hormone (ACTH) concentrations. Six mix-breed donkeys (one jack and five non-pregnant jennies) fulfilling inclusion criteria were subjected to dexamethasone suppression test (DST), thyrotropin-releasing hormone stimulation test (TRH) and combined DST-TRH challenge. Tests were interpreted according to guidelines for PPID diagnosis in horses. RESULTS: Donkeys fulfilling inclusion criteria were diagnosed with PPID by TRH stimulation test (six of six). Both DST (three of six) and DST-TRH (4/6) challenges failed to detect those animals and showed conflicting results. Similarly, cortisol basal concentrations were not consistent with PPID suspicion. MAIN LIMITATIONS: Characterisation of seasonal and geographical location effect on baseline ACTH concentrations and response to TRH is compelling in this species. Further studies with a larger number of donkeys are needed. CONCLUSIONS: This is the first study in donkeys to evaluate common dynamic tests used for PPID diagnosis in horses. Preliminary results agree with the guidelines for PPID diagnosis in horses and baseline ACTH measurement followed by TRH challenge are recommended tests for diagnosis of PPID in donkeys.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Testes Diagnósticos de Rotina/veterinária , Equidae , Doenças da Hipófise/veterinária , Adeno-Hipófise Parte Intermédia/patologia , Animais , Dexametasona/farmacologia , Feminino , Hidrocortisona/sangue , Masculino , Doenças da Hipófise/diagnóstico , Hormônio Liberador de Tireotropina/sangue , Hormônio Liberador de Tireotropina/metabolismo
15.
J Endocrinol Invest ; 42(6): 667-671, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30367433

RESUMO

BACKGROUND: Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain. AIM: To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI. METHODS: We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH. RESULTS: Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11-0.75); p = 0.011] in a model adjusted by age, sex and ACE-27. DISCUSSION: Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.


Assuntos
Envelhecimento , Hospitalização/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Glândula Tireoide/fisiopatologia , Hormônio Liberador de Tireotropina/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Testes de Função Tireóidea
16.
Behav Brain Res ; 360: 255-261, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30529403

RESUMO

Fatigue is a common symptom in many diseases and disorders and can reduce quality of life, yet lacks an adequate pharmacological intervention. To identify and develop such interventions, and to better understand fatigue, additional preclinical research is necessary. However, despite numerous mouse behavioral assays reportedly detecting fatigue-like behavior, the assumption that fatigue-like behavior is detected in many assays has not been validated through a cross-assay study. Thus, we modeled fatigue in mice by administering 5-fluorouracil, a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in mice, then evaluated its effects via voluntary wheel running activity (VWRA), locomotor activity in the open field test (OFT), immobility in the forced swim test (FST), and distance run in the treadmill fatigue test (TFT) and treadmill exercise capacity test. Additionally, taltirelin or methylphenidate was administered to alleviate fatigue-like behavior. As a result of 5-fluorouracil treatment, VWRA and the TFT were markedly reduced, indicating fatigue. The OFT, FST, and treadmill exercise capacity test, however, failed to detect fatigue-like behavior. Interestingly, both taltirelin and methylphenidate alleviated fatigue-like behavior in TFT. These data suggest that, of the current assays, only the TFT and VWRA should be expected to detect fatigue-like behavior. Moreover, this study provides additional evidence that taltirelin may provide a novel treatment for chemotherapy-induced fatigue and warrants further evaluation as an anti-fatigue therapeutic.


Assuntos
Antimetabólitos Antineoplásicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Fadiga/induzido quimicamente , Fadiga/tratamento farmacológico , Fluoruracila/toxicidade , Nootrópicos/uso terapêutico , Análise de Variância , Animais , Peso Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Modelos Animais de Doenças , Teste de Esforço , Comportamento Exploratório/efeitos dos fármacos , Feminino , Locomoção/efeitos dos fármacos , Metilfenidato/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Natação/psicologia , Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/uso terapêutico , Fatores de Tempo
17.
Med Hypotheses ; 122: 5-7, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30593422

RESUMO

Differentiated thyroid cancer (DTC) is markedly more common in women than men, and its occurrence and risk for poorer prognosis are associated with pregnancy. Further, it is known that there is a high frequency of co-occurrence of DTC and breast cancer. Although the underlying mechanisms that contribute to these phenomena are not entirely clear, 2 hypotheses are proposed here. First, human chorionic gonadotropin (hCG) produced by the placenta may be involved, since hCG has a similar function to stimulate the thyroid as thyroid-stimulating hormone (TSH), the latter of which is known to play a role in causing DTC and may promote breast cancer through the secretion of thyroid hormones (THs). Second, thyrotropin-releasing hormone (TRH), which is stimulated by suckling in the puerperal period, induces the secretion of not only TSH and thus indirectly THs, but also prolactin (PRL), which can accelerate the development of breast cancer. These hypotheses also explain the pregnancy-associated transient increase in breast cancer risk, while inhibition of estrogen by PRL may have a long-term preventive effect on breast cancer. Pregnancy-associated hyperthyroidism may also account for female preponderance of thyroid disease in general as well as tumors in organs that the thyroid hormone targets such as cardiac myxoma and diffuse-type gastric carcinoma.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/epidemiologia , Carcinoma/complicações , Carcinoma/epidemiologia , Gonadotropina Coriônica/metabolismo , Feminino , Átrios do Coração , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/epidemiologia , Humanos , Hipertireoidismo/complicações , Incidência , Modelos Teóricos , Mixoma/complicações , Mixoma/epidemiologia , Placenta/metabolismo , Gravidez , Complicações na Gravidez , Prognóstico , Prolactina/metabolismo , Reprodução , Neoplasias Gástricas/complicações , Neoplasias Gástricas/epidemiologia , Hormônios Tireóideos/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/metabolismo
18.
N Engl J Med ; 379(23): 2230-2236, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30575453

RESUMO

A loss-of-function variant in the gene encoding the prolactin receptor ( PRLR) was reported previously in a woman with persistent postpartum galactorrhea; however, this paradoxical phenotype is not completely understood. Here we describe a 35-year-old woman who presented with idiopathic hyperprolactinemia that was associated with a complete lack of lactation after each of her two deliveries. She is a compound heterozygote for loss-of-function variants of PRLR. Her unaffected parents are heterozygotes. These findings are consistent with previous work showing that mice deficient in functional Prlr do not lactate.


Assuntos
Hiperprolactinemia/genética , Transtornos da Lactação/genética , Mutação com Perda de Função , Receptores da Prolactina/genética , Adulto , Feminino , Variação Genética , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Linhagem , Prolactina/sangue , Hormônio Liberador de Tireotropina
19.
Curr Sports Med Rep ; 17(12): 454-456, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30531463

RESUMO

This case report presents the utility of the thyroid-releasing hormone (TRH) stimulation test for assessing endocrine disease in athletes. On two occasions, 4 years apart (1992 and 1996), a TRH stimulation test was performed to corroborate clinical symptoms and observation. On the first occasion, the patient's symptoms were not attributed to thyroid disease. He was treated for a sinus infection with amoxicillin/clavulanate 500 mg three times per day for 1 wk. On the second occasion, thyroid disease was confirmed and treatment with 100-µg L-thyroxine was initiated. Baseline screening and TRH stimulation testing were used at both assessment time points. Baseline screen for TSH was 2.2 and 1.2 uUI·mL and stimulated TSH was at 15.2 uUI·mL at 30 min and 30.6 uUI·mL at 45 min for the first (1992) and second (1996) assessment, respectively. Patient was positive on the second visit for antithyroglobulin antibodies at 70 IU·mL (normal, 0-59 IU·mL). Three months postdiagnosis, TSH was 0.66 uIU·mL and the patient was asymptomatic. At the most recent visit, 20 years and 4 months later, no symptomology was reported and TSH was 0.55 uIU·mL A greater understanding of the interaction between stress and end organ function is warranted in occupations undergoing unique stressors.


Assuntos
Atletas , Doenças da Glândula Tireoide/diagnóstico , Glândula Tireoide/fisiologia , Glândula Tireoide/fisiopatologia , Hormônio Liberador de Tireotropina/análise , Adulto , Autoanticorpos/sangue , Humanos , Masculino , Doenças da Glândula Tireoide/terapia
20.
Cell Physiol Biochem ; 50(1): 378-384, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30286449

RESUMO

Thyrotropin releasing hormone (TRH; pGlu-His-ProNH2) is expressed also in pancreatic ß cells where it is colocalized in secretory granules with insulin. High perinatal changes of the TRH gene expression and TRH concentrations in rat pancreatic islets coincide with the perinatal maturation of the adequate insulin secretory responsiveness to glucose and other nutrient secretagogues. TRH secretion from pancreatic islets is stimulated by glucose and inhibited by insulin. Disruption of the TRH gene in knockout mice results in hyperglycemia accompanied by impaired insulin secretory response to glucose. Progress in understanding TRH - insulin relations may be substantial for improving knowledge of pathophysiological mechanisms included in changes of insulin secretion with possible clinical impact. Block of the last step of biosynthesis of α-amidated peptides, including TRH by disulfiram (DS) treatment of adult male rats subcutaneously with 200 mg/kg for five days in our experiments resulted in barely detectable levels of peptidyl-glycine α-amidating monooxygenase (PAM) in their pancreatic islets. TRH in physiological concentration (1 nM) does not affect basal insulin secretion from intact rat pancreatic islets. In contrast, basal insulin secretion from islets of DS-treated rats is four times higher compared to controls and could not be further stimulated by high-glucose. The addition of 1 nM TRH into medium decreased immediately basal insulin secretion in DS (TRH lacking) islets to control level and normalized also their response to glucose. Interestingly, absence of the secretory response to glucose in islets from TRH depleted rats was connected with their increase of insulin content during stimulation. Glucose stimulation together with 1 nM TRH normalized also insulin content in DS islets. Apparently, high insulin content in islets from TRH depleted animals is a result of block of regulatory secretion pathway redirected to constitutional secretion which was corrected by the addition of TRH. Type 2 diabetes mellitus is a disease characterized by various range from predominant insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance. These symptoms suggest a possible role of TRH dysregulation. In conclusion, presence of TRH in ß cells ensures appropriate low basal (constitutive) insulin secretion. Release of TRH induced by glucose and possibly by other secretagogues has autocrine effect resulting in directing insulin secretion to regulatory pathway reacting to stimulation. If some defects of insulin secretion could be treated by TRH, various ways of applications (also oral and nasal) could be utilized. Moreover, positive side effects shown in animal experiments may accompany the treatment: TRH has the potential to prevent apoptosis and promotes insulin-producing cell proliferation and has also aging-reversing properties.


Assuntos
Insulina/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Dissulfiram/farmacologia , Glucose/farmacologia , Secreção de Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo
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