The CNS plays a pivotal role in the events leading to puberty by controlling anterior pituitary function via the secretion of hypothalamic factors, and the ovary via pituitary hormones and direct neural inputs. Also, it is now becoming clear that specific intraovarian regulators play important roles as puberty approaches. Thus, a drug capable of affecting any one of the portions of the reproductive axis during the pubertal process could cause serious manifestations to occur, which may affect the otherwise normal series of events during pubertal development. These studies are designed to obtain information, which will allow us to better understand the detrimental effects and mechanisms(s) of action of ethanol (ETOH) on the pubertal process. The overall goal is to learn more about influences of insulin-like growth factor-1 (IGF-1), the activation of POU homeodomain genes and transforming growth factor-alpha (TFG-alpha) on critical brain events leading to mammalian puberty and on the influences of ETOH on their actions and interactions. Also, since prepubertal ovarian steroid production is essential for puberty, we will assess the effects of ETOH on specific intraovarian proteins and peptides involved in the steroidogenic capabilities of the maturing ovary. In vivo and in vitro techniques will be utilized following chronic and acute ETOH exposure to address what effects the drug may have on these substances and their respective influence on puberty related events. In mice, we will separate the effects of ETOH on growth hormone (GH)-dependent and GH-independent actions on IGF-1 synthesis at puberty using transgenic mice which overexpress GH. In rats, we will a) assess ETOH's effects on the synthesis and actions of IGF-1, POU, and TFG-alpha with these results being correlated with assessments of hypothalamic, pituitary and ovarian hormones, as well as with other specific indices of puberty; b) assess ETOH's effects on TGF- alpha and Orexin-B on luteinizing hormone secretion in vivo; c) assess ETOH's effects and mechanisms(s) of action on their respective abilities to induce LH-releasing hormone section in vitro; and d) assess ETOH's potential effect to alter intraovarian steroidogenic acute regulatory peptide (StAR) and the ovarian steroidogenic responsiveness to specific protein and peptide hormones. In the rhesus monkey, we will assess ETOH's effects on a) puberty related hormones, hypothalamic and pituitary responsiveness, and the timing of ovulatory competency, as well as b) on specific intraovarian systems governing innervation and steroidogenesis. This research is intended to identify consequences of ETOH consumption with regard to hormonal events and their actions controlling female pubertal development.
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