The CNS plays the pivotal role in the synchronization of 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. This being the case, a drug that is 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 mechanism(s) of action of ethanol (ETOH) on the pubertal process. In recent years it has been shown that the administration of either N-methyl-DL-aspartic acid (NMDA) or neuropeptide Y (NPY) will advance the pubertal process. There is also some evidence now that specific growth factors [i.e., insulin-like growth factor I (IGF-I), epidermal growth factor (BGF) and nerve growth factor (NGF)] may also be involved. In vivo and in vitro techniques will be used, following short-term and acute ETOH exposure to address the following: IN THE RAT: The overall goal is to determine what effect(s) ETOH may have on the above substances and their respective influence on puberty related events. Specifically, we will: a) assess ETOH's effects on the synthesis of their specific mRNA, and/or in some cases, receptor mRNA, via RNase protection assays. These results will be correlated with assessments of hypothalamic, pituitary and ovarian hormones, as well as with other specific indices of puberty, b) assess ETOH's effects on NMDA, NPY and growth factor-mediated secretion of specific LH and GH controlling hypothalamic peptides in vitro, c) assess ETOH's effects on their respective abilities to elicit the pulsatile secretion of LH and GH in vivo, d) assess ETOH's potential effect to alter the extrinsic ovarian innervation by altering synthesis of ovarian NGF, or the low affinity (p75) of high affinity (trkA) NGF receptors, and e) assess the in vitro effects of ETOH on IGF-I, GH and vasoactive intestinal peptide facilitory actions on ovarian steroid release. IN THE RHESUS MONKEY: The overall goal is to determine ETOH's potential effects on the pubertal process in primates. Specifically, we will: f) assess ETOH's effects on the extrinsic ovarian innervation and on the factors governing this innervation, as well as on the developmentally regulated ovarian neurons we have recently described in this species, and g) assess ETOH's effects on the timing and progression of pubertal increases in IGF-I, GH, LH and estradiol, and on the age at first menarche.
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