During the past few years, there has been an alarming increase in adolescent and teen-age ethanol (ETOH) abuse and a growing concern for its possible medical consequences. One of the most fascinating aspects of endocrinology occurs during this period of time and that is the complex series of events that lead to reproductive maturity. The overall goal of the proposed studies is to obtain information which will allow us to better understand the detrimental effects and mechanism(s) of action of ETOH on the pubertal process. Both in vivo and in vitro techniques will be used following short-term and acute ETOH exposure to answer the following questions: IN THE RAT - a) what effect does ETOH have on specific neuropeptides and neuromodulators known to affect GH and LH release via hypothalamic actions and how does each correlate with pubertal onset, b) what are the effects of specific growth factors and excitatory amino acids at the time of puberty and what effect does ETOH have on them and their ability to influence puberty, c) what effect will ETOH have on the pubertal process and hormonal substances involved following longer exposure and what is the prognosis of recovery or reversibility after removal of the drug from the diet, d) when administered, can specific neuropeptides or other neuromodulators, or growth factors override the detrimental effects of ETOH on puberty, and e) what effect does ETOH have on the extrinsic sympathetic and sensory ovarian innervation, and what effect does ETOH have on ovarian content and responsiveness to peptides, specifically VIP, a peptide known to be involved in prepubertal ovarian development. IN THE RHESUS MONKEY f) what effect does prepubertal ETOH exposure have on the extrinsic ovarian innervation and on the developmentally regulated ovarian neurons that we have recently described in this species, and G) to gain some insight as to ETOH's potential effects on the timing and progression of pubertal increases in serum LH and E2, and on the age at menarche.
