BIOLOGY OF REPRODUCTION 40, 920-928 (1989) 920 Amplitude Modulation of the Nightly Melatonin Rise in the Neonatal Lamb and the Subsequent Timing of Pubertyl DOUGLAS L. FOSTER,2 FRANCIS J. P. EBLING, LEE E. CLAYPOOL,3 RUTH I. WOOD, TOVAGHGOL E. ADEL, and WILLFRIED SCHRAMM Reproductive Sciences Program Departments of Obstetrics and Gynecology, Biology, and Physiology The University of Michigan Ann Arbor, Michigan 48109-0404 ABSTRACT Spring-born female lambs require a decrease in day length for the normal timing of puberty the following autumn. If this decrease occurs early in postnatal life (i.e. 0-10 weeks), puberty is delayed. This study tested the hypothesis that failure of the neonatal lamb to respond to the critical long-day to short-day signal is due to inadequate nocturnal melatonin secretion. The approach was to artificially increase, to adult levels, the low nighttime rises of melatonin during the early postnatal period. Eight female lambs served as controls; they were raised on short days until 17 wk of age, and then exposed to 5 wk of long days, after which they were returned to short days. This alternating sequence of photoperiods during mid-development would be expected to induce normal puberty. Sixteen experimental females were exposed to the critical block of long days much earlier; they were placed in long days between 2 and 7 wk of age and in short days thereafter. Half (n = 8) received no further treatment. The other half (n = 8) were infused nightly with melatonin during the 8-h dark phase of the 5-wk, long-day photoperiod. This increased the amplitude of the natural nighttime melazonin rises 3- to 4-fold, well into the adult range. In most uninfused lambs exposed to long days as neonates, puberty was delayed relative to controls (33 ± 1 wk, n = 7 of 8) that experienced the 5 wk of long days at an older age, only 2 of 8 lambs treated neonatally with long days exhibited repetitive reproductive cycles by the end of the study at 44 wk. Supplementation of the neonatal nocturnal melatonin rises was without effect; only 1 of 8 melatonin-infused lambs attained puberty. The inference from these results is that the low-amplitude melatonin rhythm of the neonatal lamb does not limit the induction of puberty by seasonal light cues. Rather, the failure of early long-day exposure to induce puberty several weeks later is probably due to a postpineal gland deficiency related to immaturity of the reproductive axis itself or to growth-related signals indicating that somatic development is inadequate. INTRODUCTION Photoperiod is an important external cue governing the tempo of sexual maturation in the female sheep Accepted December 14, 1988. Received September 14, 1988. tTlus work was supported by research and training grants from the NIH (HD-07048. HD-18258, lID-I 8394 and Biomedical Support to the Vice Presi- dent for Research at The University of Michigan), a Fuibright Travel Award and Fogarmy Fellowship (TW03766 to FJ.P.E) and a Regents Fellowship from The University of Michigan (R.I.W.). A preliminary report of this work has appeared in the Program of the First Annual Meeting of the Society for Re- search on Biological Rhythms, Charleston, SC, 1988 (Abstract 13). 2Rcprint requests: Douglas L. Foster, Room 1101 SW, 300 North Ingalls Building. The University of Michigan, Ann Arbor, Ml 48109-0404. 3Present address: Wisconsin Regional Primate Research Center, 1223 Cap- itol Court, Madison, WI 537 15-1299. (Foster et a!., 1986). For spring-born female Suffolk lambs, the decreasing day lengths of autumn are neces- sary for the initiation of the first reproductive cycle (Yellon and Foster, 1985; Foster Ct al., 1988a). Puberty does not occur at the appropriate age, however, if the decrease in day length is experienced very early in life, for example in the first 10 wk (Foster, 1983; Yellon and Foster, 1985). The reason for the failure of the repro- ductive response in this case is not clear. It could be due to an inability of the pineal gland of the lamb to produce a melatonin rhythm that reflects ambient day length, as is the case in neonatal rodents (Tamarkin et a!., 1980). Alternatively, it may result from an inability of the developing reproductive axis to respond to photoperiod changes, analogous to the failure of inhibi- tory photoperiods to retard reproductive development in the Syrian hamster (Darrow et a!., 1980). The present