THE AMPLITUDE OF NOCTURNAL MELATONIN CONCENTRATIONS IS NOT DECREASED BY ESTRADIOL AND DOES NOT ALTER REPRODUCTIVE FUNCTION IN ADOLESCENT ORADULT FEMALE RHESUS-MONKEYS

Nocturnal concentrations of melatonin in serum decline significantly w ith advancing pubertal development in both children and non-human prim ates and elevated levels may be associated with anovulation in adults. Three studies, using female rhesus monkeys, were performed to determi ne whether (1) the decline in nocturnal melatonin concentrations in ad olescents was due to maturational increases in serum oestradiol, (2) t he experimental elevation in nocturnal melatonin would delay the norma l progression of puberty in post-menarchial monkeys, and (3) the exper imental elevation in nocturnal melatonin would disrupt normal ovulator y function in adults. In experiment 1, juvenile female rhesus monkeys, housed indoors in a fixed photoperiod (12 h light: 12 h darkness), we re assigned randomly to one of two treatment groups: ovariectomized wi th no replacement therapy (control; n = 4) or ovariectomized with oest radiol replacement therapy maintaining oestradiol at approximately 90 pmol/l (treated; n = 8). Twenty-four hour as well as daytime serum sam ples were collected from 19 to 35 months of age. Nocturnal melatonin c oncentrations declined significantly in all females with advancing chr onological age and this change was unaffected by oestradiol treatment. The decline in nocturnal melatonin concentrations occurred, on averag e, 2.0 +/- 0.2 months after the initial rise in serum LH in control fe males and 6.0 +/- 0.8 months in treated females. Furthermore, this dec line in night-time melatonin was not related to significant developmen tal changes in body weight. In experiment 2, control (n = 6) and melat onin-treated (treated; n = 6) adolescent female monkeys were studied f rom - 30 to + 105 days from menarche. Beginning at 45 days following m enarche, treated females received 30 days of nocturnal melatonin infus ion to elevate levels to prepubertal values. Developmental changes in perineal swelling and coloration as well as serum oestradiol and insul in-like growth factor-I (IGF-I) were compared with values observed dur ing the 45-day pretreatment and 30-day post-treatment conditions as we ll as with those observed in control females. Despite a significant el evation in nightly melatonin levels for the 30-day period in treated f emales, developmental changes in oestradiol, IGF-I, and perineal color ation and swelling were not different compared with the control female s. In experiment 3, adult females were given melatonin nightly beginni ng on the first day of menses following an ovulatory cycle and treatme nt was continued for 45 days or until the next menstruation occurred. Melatonin was elevated to supraphysiological levels every night throug hout the treatment period. Despite this elevation, an ovulation, infer red from serum progesterone levels, occurred in every female and serum oestradiol, LH or progesterone were not affected compared with the va lues obtained during the untreated cycle. These data indicate that the decline in nocturnal melatonin concentrations is not related to a dev elopmental increase in oestradiol secretion. Furthermore, experimental ly elevated concentrations of nocturnal melatonin did not delay the no rmal progression of puberty following menarche nor did it disrupt ovul atory function in adults. These data suggest that the enhanced nocturn al melatonin concentrations are not causally linked to either puberty onset or anovulatory conditions in adults.