These data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion while in hypergonadotrophic hypogonadal males melatonin secretion is decreased. Testosterone treatment normalized melatonin concentrations in these patients. Taken together, the results suggest that GnRH, gonadotrophins and gonadal steroids modulate pineal melatonin in humans.

Recently we have demonstrated that melatonin secretion is increased in untreated male patients with GnRH deficiency. Testosterone administration to these patients decreased melatonin secretion to normal levels. These data, however, did not exclude a gonadotropic effect on melatonin secretion. To further elucidate whether gonadal steroids and/or gonadotropins modulate melatonin secretion in humans we compared untreated young males with hypogonadotropic hypogonadism (IGD, n = 6), and hypergonadotropic hypogonadism caused by KlinEfelter's syndrome (KS, n = 11) to normal pubertal male controls (n = 7). KS patients were subdivided into two groups: KS-1, with low testosterone; and KS-2, with normal testosterone levels. Serum samples for melatonin concentrations were obtained every 15 min from 7 PM to 7 AM in a controlled light-dark environment with simultaneous sleep recordings. All KS patients had elevated gonadotropin levels and decreased melatonin levels. Mean (+/- SD) dark-time nocturnal melatonin levels in KS-1 were 92 +/- 21 pmol/L and were 146 +/- 46 pmol/L in KS-2 compared with 178 +/- 64 pmol/L in controls. Integrated nocturnal melatonin secretion values (AUC) were 64 +/- 14 pmol/min x L x 10(3) in KS-1 and 96 +/- 29 pmol/min x L x 10(3) in KS-2 compared with 116 +/- 42 pmol/min x L x 10(3) in controls. All IGD patients had low gonadotropin and testosterone levels. Their dark-time melatonin levels (286 +/- 26 pmol/L) and the AUC values (184 +/- 15 pmol/min/L x 10(3)) were increased. These data indicate that melatonin secretion is increased in male patients with GnRH deficiency and decreased in low testosterone hypergonadotropic hypogonadal patients. Taken together, our results suggest that both gonadotropins and gonadal steroids modulate melatonin secretion in humans.

Melatonin secretion is decreased in male patients with low testosterone hypergonadotrophic hypogonadism whereas in normal testosterone Klinefelter's syndrome patients, melatonin secretory profiles are normal. The results suggest that the suppression of melatonin secretion in these patients is mediated by GnRH (either directly or indirectly) and/or oestradiol.