RESUMO
Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises form an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The lightdark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.
Assuntos
Humanos , Animais , Ritmo Circadiano/fisiologia , Ingestão de Alimentos/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Estresse Fisiológico/fisiopatologiaRESUMO
The existence of a circadian rhythm of atrial natriuretic peptide (ANP) in humans is controversial. We studied the plasma ANP response to isotonic blood volume expansion in the morning and in the afternoon and its relationship with adrenocorticotropic hormone (ACTH)-cortisol diurnal variation in seven normal subjects. Basal plasma ANP level was similar in the morning (19.6 + 2.4 pg/ml) and in the afternoon (21.8 + 4.8 pg/ml). The ANP peak obtained with saline infusion (0.9 percent NaCl, 12 ml/Kg) in the morning (49.4 + pg/ml) did not differ from that obtained in the afternoon (60.3 + 10.1 pg/ml). There was no correlation between the individual mean cortisol and ACTH levels and the ANP peak obtained with saline infusion. These data indicate no diurnal variation in plasma ANP secretion induced by blood volume expansion and no relationship between plasma ANP peak and ACTH-cortisol diurnal variation.
Assuntos
Adulto , Feminino , Humanos , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Fator Natriurético Atrial/biossíntese , Hidrocortisona/metabolismo , Hipófise/metabolismo , Cloreto de Sódio/administração & dosagem , Hormônio Adrenocorticotrópico/sangue , Fator Natriurético Atrial/sangue , Ritmo Circadiano/fisiologia , Hidrocortisona/sangueRESUMO
Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R)) gene in affected Kindreds. In most Kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R) gene in a affected Kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R) gene have also been reported. In the present study, we analyzed exon 3 of the V2(R) gene in 20 unrelated individuals by direct sequencing. A C(T alteration in the third position of codon 331 (AGC(AGT), which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome.
Assuntos
Humanos , Diabetes Insípido Nefrogênico/genética , Polimorfismo Genético/genética , Receptores de Vasopressinas/genética , Reação em Cadeia da PolimeraseRESUMO
Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76 percent of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19 percent), V281L (18 percent), and IVS2,A/C>G,-12 (15 percent). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38 percent), in the SV form it was I172N (53 percent), and in the NC form it was V281L (57.7 percent). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH
Assuntos
Pré-Escolar , Humanos , Masculino , Feminino , Lactente , Criança , Hiperplasia Suprarrenal Congênita , Conversão Gênica , Mutação Puntual , /genética , Alelos , Estudos de Coortes , Genótipo , Fenótipo , Reação em Cadeia da PolimeraseRESUMO
Salivary cortisol is an index of plasma free cortisol and is obtained by a noninvasive procedure. We have been using salivary cortisol as a tool for physiological and diagnostic studies, among them the emergence of circadian rhythm in preterm and term infants. The salivary cortisol circadian rhythm in term and premature infants was established between 8 and 12 postnatal weeks. In the preterm infants the emergence of circadian rhythm was parallel to the onset of sleep rhythm. We also studied the use of salivary cortisol for screening for Cushing's syndrome (CS) in control and obese outpatients based on circadian rhythm and the overnight 1 mg dexamethasone (DEX) suppression test. Salivary cortisol was suppressed to less than 100 ng/dl after 1 mg DEX in control and obese patients. A single salivary cortisol measurement at 23:00 h and again after 1 mg DEX above the 90th percentile of the obese group values had sensitivity and specificity of 93 and 93 percent (23:00 h), and 91 and 94 percent (after DEX), respectively. The sensitivity improved to 100 percent when we combined both parameters. We also studied 11 CS children and 21 age-matched primary obese children for whom salivary cortisol sensitivity and specificity were 100/95 percent (23:00 h), and 100/95 percent (1 mg DEX), respectively. Similar to adults, sensitivity and specificity of 100 percent were obtained by combining 23:00 h and 1 mg DEX. The measurement of salivary cortisol is a useful tool for physiological studies and for the diagnosis of CS in children and adults on an outpatient basis.
Assuntos
Humanos , Feminino , Recém-Nascido , Lactente , Adolescente , Adulto , Ritmo Circadiano , Síndrome de Cushing/diagnóstico , Hidrocortisona/análise , Saliva/química , Síndrome de Cushing/metabolismo , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Obesidade/metabolismo , Saliva/metabolismo , Sensibilidade e EspecificidadeRESUMO
Osteoporosis is a common manifestation of Cushing's syndrome, but the mechanisms responsible for this abnormality have not been defined. With the objective of analyzing parathyroid hormone (PTH) secretion in chronic hypercortisolism (CH), we evaluated 11 healthy subjects and 8 patients with CH, 6 with Cushing's disease and 2 with adrenal adenoma. These volunteers were submitted to tests of PTH stimulation through hypocalcemia (EDTA), PTH suppression through hypercalcemia (iv and oral calcium), and evaluation of bone mineral density (BMD) by DEXA. During the test of PTH stimulation, the calcium and magnesium concentrations of the normal and CH groups were similar. Patients with CH showed an increased PTH response to the hypocalcemic stimulus compared to controls. PTH values were significantly higher in the CH group at 70 (17.5 ± 3.5 vs 10.2 ± 1.3 pmol/l, P = 0.04), and 120 min (26.1 ± 5.9 vs 11.3 ± 1.9 pmol/l, P = 0.008) of EDTA infusion. The area under the curve for PTH during EDTA infusion was also significantly higher in patients with CH than in normal subjects (1867 ± 453 and 805 ± 148 pmol l-1 2 h-1, P = 0.02). During the test of PTH suppression, calcium, magnesium and PTH levels of the patients with hypercortisolism and controls were similar. BMD was decreased in patients with hypercortisolism in the spine (0.977 ± 0.052 vs 1.205 ± 0.038 g/cm² in controls, P<0.01). In conclusion, our results show that subjects with CH present decreased bone mass mainly in trabecular bone. The use of dynamic tests permitted the detection of increased PTH secretion in response to a hypocalcemic stimulus in CH patients that may probably be involved in the occurrence of osteoporosis in this state
Assuntos
Humanos , Masculino , Feminino , Adulto , Hiperfunção Adrenocortical , Hormônio Paratireóideo , Adenoma , Neoplasias das Glândulas Suprarrenais , Densidade Óssea , Cálcio , Doença Crônica , Síndrome de Cushing/metabolismo , Ácido Edético , Magnésio , Osteoporose , Hormônio ParatireóideoRESUMO
This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways.
Assuntos
Camundongos , Ratos , Animais , Glândulas Suprarrenais/fisiologia , Hormônio Adrenocorticotrópico/biossíntese , Fator Natriurético Atrial/metabolismo , Comportamento Alimentar/fisiologia , Hipotálamo/fisiologia , Hipófise/fisiologia , Fator Natriurético Atrial/biossínteseRESUMO
This study was undertaken to determine the short-loop negative feedback at the hypothalamic site after adrenalectomy (ADX), when the hypothalamic-pituitary axis was at different set-points. Rats were submitted to the experimental procedure 3 h and 1, 3, and 14 days after bilateral ADX or sham surgery under ether anesthesia by the dorsal approach. ADX rats were supplied with 1.5 per cent NaCl. After decapitation, plasma samples were collected and corticosterone (B) and adrenocorticotrophic hormone (ACTH) concentrations were determined by radioimmunoassay (RIA). Using in vitro incubation of the median basal hypothalamus (MBH) fragment we studied the hypothalamic corticotrophin-releasing hormone (CRH) release under basal conditions and under the inhibitory effect of ACTH. Hypothalamic CRH secretion, determined by direct RIA, with out extraction and reported as pg CRH/MBH per 1 h incubation, was inhibited by ACTH administration in a dose-dependent manner, demonstrated by a significant negative correlation obtained by linear regression analysis of CRH secretion as a function of ACTH dos However, the percentage of inhibition of CRH secretion was higher at 1 and 3 days than at 14 days after ADX. In conclusion, these in vitro studies demonstrated that ACTH suppressed basal CRH secretion in a dose dependent manner, an effect compatible with a short-loop feedback mechanism. Furthermore, we demonstrated variable suppressibility of CHR secretion by ACTH at different times after ADX.
Assuntos
Ratos , Animais , Masculino , Adrenalectomia , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Hipotálamo/metabolismo , Técnicas In Vitro , Glucocorticoides/metabolismo , Ratos WistarRESUMO
1. The possible correlation between secretions of adrenocorticotropic hormone (ACTH) and of ß-lipotropin (ß-LPH), two pro-opiomelanocortin (POMC)-derived peptides, was investogated in 27 normal subjects under basal conditions (circadian rhythmz0, after the administration of 1 mg dexamethasone and in tests involving acute (human corticotropin releasing hormone, hCRG, and insulin tolerance test, ITT) and chronic (metyrapone) simulation. 2. All subjects presented circadian rhythm and an operating negative feedback mechanism. Plasma ACTH and ß-LPH concnetrations were correlated in al tests. The increase in ACTH and ß-LPH levels after hCRH was lower than that detected after ITT, though both increases were more discrete than those detected after stimulation with metyrapone. 3. The data suggest that, under hypoglycemic conditions, ACTH and ß-LPH secretion involves other POMC secretagogues in addition to endogenous CRH. The batyre of these factore remains undefined. The greater efficacy of metyrapone treatment in elevating ACTH and ß-LPH levels is most likely mediated by sustained reduction in cortisol production and interrruption of the rapid steroid feedback on the pituitary. The molar peak ratios of the acute tests, vere similar to one another, differed from the peak ratio obtained during the metyrapone test, suggesting that corticotrophs may present polls with differentiated ACTH and ß-LPH content and release according to the type and/or duration of the stimulus
Assuntos
Adulto , Humanos , Masculino , Feminino , Hormônio Adrenocorticotrópico/sangue , beta-Lipotropina/sangue , Dexametasona/farmacologia , Hormônio Liberador da Corticotropina/sangue , Hipoglicemia/sangue , Metirapona/farmacologia , Hormônio Adrenocorticotrópico/metabolismo , beta-Lipotropina/metabolismo , Ritmo Circadiano , Insulina/sangue , Insulina/farmacologia , RadioimunoensaioRESUMO
Dosou-se aldosterona em soro e saliva de individuos normais, atraves de radioimunoensaio com extracao previa, obtendo-se os valores medios de 9,5ng/100ml e 8,8ng/ 100ml, respectivamente. O estudo da correlacao entre estes valores revelou um coeficiente de 0,82. A vantagem de obter valores de aldosterona salivar e a possibilidade de estudos em circunstancias em que o stress da puncao venosa interfere na analise dos resultados e em situacoes em que se necessitam colheitas sanguineas seriadas (p.ex., ritmo hormonal)
Assuntos
Adulto , Humanos , Masculino , Aldosterona , Doadores de Sangue , SalivaRESUMO
This study was designed to determine the relationship between endogenous hyperinsulinemia or free fatty acid (FFA) levels and the abnormal release of growth hormone (GH) during the oral glucose tolerance test (OGTT) or in response to thyrotropin releasing hormone (TRH) in acromegalic patients. Seventeen patients with acromegaly and nine healthy control subjects were studied. The 12 acromegalic patients who did not show the paradoxical response of increased GH secretion to the OGTT an/or to TRH exhibited higher insulin levels (total area under the curve during the OGTT) than patients who did. However, the FFA levels of the groups of acromegalic patients were similar. These data suggest that the endogenous hyperinsulinemia exhibited by many patients with acromegaly is associated with the absence of the paradoxical increase in GH secretion during the OGTT and/or after TRH
Assuntos
Humanos , Masculino , Feminino , Acromegalia/metabolismo , Hormônio do Crescimento/sangue , Insulina/sangue , Hormônio Liberador de Tireotropina/farmacologia , Teste de Tolerância a GlucoseRESUMO
1. To evaluate different degrees of 21-hydroxylase (21-OH) deficiency we studied the 17-hydroxyprogesterone (17-OHP) and cortisol response to the adrenocorticotropin hormone (ACTH) stimulation test. In a study of 13 families we characterized the relatives of patients with classical 21-OH deficiency using HLA antigen typing and the ACTH test. The subjects were divided into five groups: 12 patients with the classical form, 11 patients with the nonclassical form, 38 heterozygotes, 6 normal homozygotes and 33 controls. 2. The 17-hydroxyprogesterone response to ACTH (mean +/- SD) varied as follows according to the degree of 21-OH deficiency: 25442 +/- 15718 ng/dl for the classical group, 4198 +/- 1637 ng/dl for the nonclassical group, 348 +/- 267 ng/dl for the heterozygotes, 127 +/- 81 ng/dl for normal homozygotes, and 164 +/- 120 ng/dl for the controls. Basal plasma cortisol did not differ among the five groups. The cortisol response to ACTH was not different among controls (30 +/- 8 micrograms/dl), normal homozygotes (28 +/- 7 micrograms/dl) and heterozygotes (26.5 +/- 7 micrograms/dl). The cortisol response was decreased in the patient groups and was lower in the classical (14 +/- 10 micrograms/dl) than in the nonclassical group (20 +/- 4 micrograms/dl). 3. In most families (11/13), HLA typing was informative in identifying the 21-OH deficiency containing haplotype, which correlated with the hormonal profile. In two families there was no correlation between the HLA genotype and the clinical expression of 21-OH activity for two HLA identical pairs of siblings
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Hormônio Adrenocorticotrópico/farmacologia , Esteroide 21-Hidroxilase/deficiência , Teste de Histocompatibilidade , Hidrocortisona/metabolismo , Hidroxiprogesteronas/metabolismo , Fatores de TempoRESUMO
In the present study, we investigated the effects of cannabidiol (CBD) on plasma prolactin, growth hormone and cortisol of 11 normal volunteers who received placebo or CBD at the doses of 300 mg (N = 7) or 600 mg (N = 4), po, in a double-blind manner during two experimental sessions separated by an interval of at least one week. The sessions were held in the morning and consisted of blood collection and application of self-evaluation scales before and after drug injection (-35 to 180 min). Hormonal measurements were performed by radioimmunoassay. Basal prolactin (11.5 +/- 4.3 ng/ml) and growth hormone (1.5 +/- 0.7 ng/ml) levels were unchanged after placebo and CBD. In contrast, plasma cortisol levels decreased significantly during the placebo sessions (basal measurement = 11.0 +/- 3.7 micrograms/dl; 120 min after placebo = 7.1 +/- 3.9 micrograms/dl), in agreement with the normal circadian rhythm of this hormone. This decrease in cortisol levels was significantly attenuated after CBD (basal measurement = 10.5 +/- 4.9 micrograms/dl; 120 min after 300 mg CBD = 9.9 +/- 6.2 micrograms/dl; 120 min after 600 mg CBD = 11.6 +/- 11.6 micrograms/dl). CBD was also found to have a sedative effect as determined by the self-evaluation scales. The present results suggest that CBD interferes with cortisol secretion
Assuntos
Humanos , Masculino , Adulto , Canabidiol/farmacologia , Hormônio do Crescimento/sangue , Hidrocortisona/sangue , Prolactina/sangue , Método Duplo-Cego , Radioimunoensaio , Fatores de TempoRESUMO
Portadores de AIDS podem apresentar alteraçöes primárias e/ou secundárias do eixo hipotálamo-hipofisário-adrenocortical (EHHA), com manifestaçöes clínicas que väo de crises addisonianas a quadros de hipercortisolismo. Objeto. Avaliar o EHHA de 20 pacientes de AIDS e 17 controles normais, mediante testes de estímulo com ACTH exógeno (cosintropina, 250µg IV em bolo, com dosagem de cortisol basal e 60min após) e, subseqüentemente, teste de estímulo com hormônio liberador de corticotrofina ovino sintético (oCRH, 1µg/kg IV em bolo, com dosagens de ACTH e cortisol basais e a intervalos de 15-30min durante duas horas). Resultados. Diferente dos voluntários normais, pacientes de AIDS apresentaram estado de hipercortisolismo basal e após estímulo, tanto com cosintropina como com o CRH; cortisol (em µg/dL, média + or - cosintropina - basal 22,5 + or - 7,1 x 10,6 + or - 3,6 (p < 0,01) e após estímulo, 36,0 + or - 12,8 x 28,3 + or - 7,6 (p< 0,05); teste de oCRH - basal 19,7 + or - 9,0 x 10,1 + or - 3,4 (p < 0,01) e no pico de resposta, 27,5 + or - 8,9 x 18,3 + or 0 5,1 (p < 0,05). Além disso, a secreçäo de ACTH encontrava-se também significantemente mais elevada nos pacientes de AIDS após o teste de estímulo com o CRH; ACTH (em pg/mL) nos pacientes com AIDS x normais: teste de oCRH - basal 42,2 + or - 33,5 x 28,9 + or - 12,7 (NS) e no pico de resposta, 104,7 + or - 62,2 x 59,3 + or - 17,6 (p < 0,05). Conclusöes. Pela condiçäo de estresse continuado, os pacientes de AIDS apresentam estado de hipercortisolismo e de hipersecreçäo de ACTH, revelando resistência ao mecanismo de feedback negativo. Este fenômeno pode ser explicado pela interaçäo do sistema imunológico com o EHHA, com ativaçäo deste eixo pela liberaçäo de linfocinas circulantes que estimulariam, diretamente, hipotálamo e hipófise a produzir CRH e ACTH, respectivamente
Assuntos
Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiopatologia , Hidrocortisona , Hormônio Adrenocorticotrópico , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hidrocortisona/sangue , Cosintropina , Hormônio Adrenocorticotrópico/sangue , Sorodiagnóstico da AIDSRESUMO
Hemidecortication (HD) (left cerebral hemisphere) performed in rats with the aim of analyzing the modulating effect of the cerebral cortex on the hypothalamic-pituitary-adrenal axis. Corticosterone release induced either by or immobilization stress was evaluated in control (C) and HD rats. The percentage increase in corticosterone was greater in HD than in C rats after 15 min of ether stress (HD = 142%, C = 50%) and after 60 min of immobilization stress (HD = 197%, C = 126%). An in vitro test showed that the release of ACTH induced by corticotropin releasing hormone (CRH) from hemipituitary fragments from HD rats was not different from that in control rats. These results suggest an inhibitory effect of the cerebral cortex on the hypothalamus which may modulate the secretion of corticoptropin releasing peptides
Assuntos
Descorticação Cerebral , Éter/farmacologia , Sistema Hipófise-Suprarrenal/fisiologia , Estresse Fisiológico/fisiopatologia , Hormônio Adrenocorticotrópico/metabolismo , Corticosterona/metabolismo , Restrição FísicaRESUMO
Em 10 homens adultos normais estudou-se atraves de colheitas seriadas durante 3 horas, a secrecao basal pulsatil de hormonio luteinizante (LH), procurando correlaciona-la com a da testosterona. Os resultados obtidos demonstram uma importante e significativa correlacao dos censores superiores e inferiores dos pulsos de LH entre si, sendo,em media, os primeiros 2 vezes maiores que os ultimos.Alem disso, ambos se correlacionam positivamente com a media dos niveis plasmaticos de 3 horas. Semelhante padrao de correlacao e encontrado quando se analisa a secrecao de testosterona. Estas relacoes limitariam a oscilacao dos valores individuais, de cada paciente, a um determinado intervalo de niveis hormonais, naquele periodo de estudo. No conjunto, as observacoes obtidas favorecem a ideia de que no homem adulto, em condicoes basais, a secrecao pulsatil de LH, decorrente de um ritmo ultradiano inerente ao sistema nervoso central, poderia ter alguns dos seus parametros quantitativos refletidos na secrecao de testosterona pelos testiculos
Assuntos
Hormônio Luteinizante , TestosteronaRESUMO
A secrecao do hormonio luteinizante foi realizada em pacientes do sexo masculino com doenca de Chagas cronica e individuos controles sob condicoes basais (secrecao basal pulsatil) e de estimulo (testes do LH-RH e citrato de clomifene). O grupo chagasico mostrou uma maior dispersao dos niveis do LH integral em condicoes basais que os apresentados pelo grupo controle. A frequencia dos pulsos e a concentracao media de testosterona de 12 amostras por um periodo de 3 horas, foram normais. Alteracoes funcionais da secrecao do LH hipofisario seguindo-se infusoes aguda ou continua de LH-RH nao foram demonstradas. Entretanto, a liberacao de LH durante o teste do citrato de clomifene mostrou valores com maior dispersao, principalmente no 8o. dia no grupo chagasico em relacao ao controle. Esses resultados, provavelmente, sugerem a existencia de uma disfuncao hipotalamica na doenca de Chagas cronica