RESUMO
Although the pathogenesis of polycystic ovarian syndrome (PCOS) is still controversial, a series of investigations has demonstrated an array of neuroendocrine abnormalities as a major component of the syndrome. From a neuroendocrine perspective, patients with PCOS exhibit an accelerated frequency and/or higher amplitude of LH pulses, augmentation of LH secretory burst mass, and a more disorderly LH release. Elevated in vitro LH bioactivity and a preponderance of basic LH isoforms, which correlate positively with elevated serum 17-hydroxyprogesterone, androstenedione, and testosterone concentrations, also characterize adolescents with PCOS. Heightened GnRH drive of gonadotropin secretion and a steroid-permissive milieu appear to jointly promote elevated secretion of basic LH isoforms. Positive feedback is implied, because hypersecretion of highly bioactive LH in PCOS probably contributes to inordinate androgen output. However, the precise nature of feedback disruption remains uncertain. Indeed, recent data suggest that PCOS is marked by anomalies of both feedforward and feedback signaling between GnRH/LH and ovarian androgens. From a single hormone perspective, the individual patterns of LH and androstenedione release are consistently more irregular in patients with PCOS. Bihormonal analysis has disclosed concomitant uncoupling of the pairwise synchrony of LH and testosterone, LH and androstenedione, and testosterone and androstenedione secretion. The foregoing ensemble of findings points to deterioration of both orderly uniglandular and coordinate bihormonal output in PCOS. Additional studies are needed to establish the primary pathophysiologic mechanisms underlying this disorder.
Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Hormônio Luteinizante/metabolismo , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , 17-alfa-Hidroxiprogesterona/metabolismo , Adolescente , Adulto , Androstenodiona/sangue , Androstenodiona/fisiologia , Dopamina/metabolismo , Retroalimentação , Feminino , Glicosilação , Hormônio Liberador de Gonadotropina/fisiologia , Humanos , Resistência à Insulina/fisiologia , Modelos Biológicos , Obesidade/fisiopatologia , Ovulação/fisiologia , Adeno-Hipófise/metabolismo , Síndrome do Ovário Policístico/sangue , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Fluxo Pulsátil , Taxa Secretória , Testosterona/sangue , Testosterona/fisiologiaRESUMO
UNLABELLED: We studied the effects of chronic renal failure on the pituitary-cortisol axis and adrenal androgen function in 26 patients (16 male and 10 female), aged 6.5 to 22.5 years (mean 14.5). Ten patients were prepubertal, 8 pubertal, and 8 post-pubertal. All of them were on chronic hemodialysis. Pubic hair development was delayed in 56% of the patients. Serum cortisol was increased in 15 out of the 26 patients. Serum delta 4-androstenedione was high in 11 out of 15 patients in Tanner's stage I or II and in 1 out of 11 patients in Tanner's stage III, IV or V (p less than 0.01). Serum cortisol was elevated in 10 out of 12 patients with high serum delta 4-androstenedione and in only 5 out of 14 with normal delta 4-androstenedione (p less than 0.02). Serum dehydroepiandrosterone sulphate was normal in 22 patients and elevated in 4 males. There was a significant inverse correlation between bone age and serum cortisol (r: -0.59; p less than 0.005) and a significant positive correlation between bone age and serum dehydroepiandrosterone sulphate (r: 0.45 p less than 0.01). Serum ACTH was normal. A reduction by 50% in cortisol and 78% in dehydroepiandrosterone sulphate was found after dexamethasone suppression, but delta 4-androstenedione did not suppress after dexamethasone. After ACTH stimulation test cortisol increased by 50% and delta 4-androstenedione by 80%. CONCLUSIONS: The increased levels of cortisol and delta 4-androstenedione with partial resistance to dexamethasone suggest that these patients have a hypothalamic-pituitary dysfunction similar to that found in Cushing's disease or in chronic stress. The difference in the responses of delta 4-androstenedione and dehydroepiandrosterone sulphate observed is consistent with the existence of different mechanisms of control for these two steroids.