The amplitude of nocturnal melatonin concentrations is not decreased by oestradiol and does not alter reproductive function in adolescent or adult female rhesus monkeys
Authors: Wilson M. E. , Lackey S. , Chikazawa K. , Gordon T. P. 
Published: December 2008

Nocturnal concentrations of melatonin in serum decline significantly with advancing pubertal development in both children and non-human primates and elevated levels may be associated with anovulation in adults. Three studies, using female rhesus monkeys, were performed to determine whether (1) the decline in nocturnal melatonin concentrations in adolescents was due to maturational increases in serum oestradiol, (2) the experimental elevation in nocturnal melatonin would delay the normal progression of puberty in post-menarchial monkeys, and (3) the experimental elevation in nocturnal melatonin would disrupt normal ovulatory function in adults. In experiment 1, juvenile female rhesus monkeys, housed indoors in a fixed photoperiod (12 h light: 12 h darkness), were assigned randomly to one of two treatment groups: ovariectomized with no replacement therapy (control; n= 4) or ovariectomized with oestradiol replacement therapy maintaining oestradiol at ∼ 90 pmol/l (treated; n= 8). Twenty-four hour as well as daytime serum samples were collected from 19 to 35 months of age. Nocturnal melatonin concentrations declined significantly in all females with advancing chronological age and this change was unaffected by oestradiol treatment. The decline in nocturnal melatonin concentrations occurred, on average, 2·0 ±0·2 months after the initial rise in serum LH in control females and 6·0 ±0·8 months in treated females. Furthermore, this decline in night-time melatonin was not related to significant developmental changes in body weight.

In experiment 2, control (n = 6) and melatonintreated (treated; n =6) adolescent female monkeys were studied from −30 to +105 days from menarche. Beginning at 45 days following menarche, treated females received 30 days of nocturnal melatonin infusion to elevate levels to prepubertal values. Developmental changes in perineal swelling and coloration as well as serum oestradiol and insulin-like growth factor-I (IGF-I) were compared with values observed during the 45-day pretreatment and 30-day post-treatment conditions as well as with those observed in control females. Despite a significant elevation in nightly melatonin levels for the 30-day period in treated females, developmental changes in oestradiol, IGF-I, and perineal coloration and swelling were not different compared with the control females.

In experiment 3, adult females were given melatonin nightly beginning on the first day of menses following an ovulatory cycle and treatment was continued for 45 days or until the next menstruation occurred. Melatonin was elevated to supraphysiological levels every night throughout the treatment period. Despite this elevation, an ovulation, inferred from serum progesterone levels, occurred in every female and serum oestradiol, LH or progesterone were not affected compared with the values obtained during the untreated cycle.

These data indicate that the decline in nocturnal melatonin concentrations is not related to a developmental increase in oestradiol secretion. Furthermore, experimentally elevated concentrations of nocturnal melatonin did not delay the normal progression of puberty following menarche nor did it disrupt ovulatory function in adults. These data suggest that the enhanced nocturnal melatonin concentrations are not causally linked to either puberty onset or anovulatory conditions in adults.

Journal of Endocrinology (1993) 137, 299–309