R. Luboshitzky et al., Melatonin administered in the afternoon decreases next-day luteinizing hormone levels in men - Lack of antagonism by flumazenil, J MOL NEURO, 12(1), 1999, pp. 75-80
The role of melatonin in the regulation of human reproduction remains uncle
ar. In the present study, we examined the influence of exogenous melatonin
on pulsatile luteinizing hormone (LW), diurnal rhythm of testosterone, and
endogenous melatonin profile in six healthy young adult males. To test the
hypothesis that the effect of melatonin on LH or testosterone secretory pat
terns may be mediated through the benzodiazepine-(BNZ) gamma-amino-butyric
acid (GABA) receptor complex, a benzodiazepine receptor antagonist (Flumaze
nil) was administered. The study design comprised four 10-h (4:00 PM-2:00 A
M) testing periods. During each experimental period, subjects were given an
oral dose of placebo, or 3 mg melatonin or 10 mg flumazenil, at 5:00 PM, i
n a randomized, double-blind, partially repeated Latin square design in the
following combinations: placebo-placebo, placebo-melatonin, flumazenil-pla
cebo, and flumazenil-melatonin. The following day, serum samples were obtai
ned every 20 min between 4:00 PM and 2:00 AM in a controlled light-dark env
ironment for the determination of LH and melatonin levels. Serum testostero
ne concentrations were determined every 20 min between 7:00 and 8:00 AM and
7:00 and 8:00 PM. A significant decrease in mean serum LH levels (p < 0.02
) was observed in the melatonin-treated groups as compared with placebo-flu
mazenil groups. There was no change in LH pulse frequency, testosterone lev
els, or in melatonin onset time and amplitude. No additional effect of flum
azenil on LH or testosterone levels was observed.
These data indicate that an evening melatonin administration decreases the
next-day LH secretion in normal adult males without altering testosterone l
evels or the endogenous nocturnal melatonin secretory pattern. This effect
of melatonin is not mediated through the benzodiazepine-GABA receptor compl
ex.