The long term objective of this application is to elucidate the mechanisms controlling the onset of adult ovarian activity at puberty in female mammals. The animal model to be employed in these studies is the immature feet, in which precocious pubety can be induced by altering the photoperiod from a non-stimulatory, short day (8L:16D) to a stimulatory long-day photoperiod (16L:8D) at 15 weeks of age. We now know that exposure to long days causes two marked changes in the endocrinology of the ferret. First, the negative feedback effectiveness of estradiol on LH secretion decreases, and second, the sensitivity of the ovaries to exogenous gonadotropin stimulation increases; both occur in response to a long-day photoperiod. In this proposal, we will attempt to determine the mechanisms underlying these two phenomena. This will be done by carefully characterizing detailed patterns of gonadotropin secretion in both intact and ovariectomized, estradiol-treated females during photoperiod stimulation. The information thus obtained will be used to examine ovarian requirements for adult function. Once the gonadotropin stimulus to the ovary is characterized, it will be mimicked in females of equivalent age and body weight, which are still immature due to a non-stimulatory photoperiod. Finally, the importance of extra-hypothalamic factors to the occurrance of sexual maturation induced by increased daylength will be examined. We will place Halasz-type cuts in the brain to prevent first the anterior, then the posterior brain, from communicating with the hypothalamus. Second, the effect of changes in the light cycle on activity patterns of ferrets (running rhythms) will be used to provide an index of photoperiod response which is different from the reproductive system. Finally, by the use of hypothalamic implants to augment GnRH secretion in immature animals, we hope to develop an animal model for study of hypothalamic hamartoma: a primary cause of precocious puberty in humans.
