The effects of fetal ethanol exposure on GABA-mediated growth hormone secretion in the postnatal rat

Includes bibliographical references (pages [96]-122)Maternal EtOH consumption results in decreased birth weight and impairs postnatal growth potential, possibly due to disruption of the growth hormone (GH) regulatory system. Previous studies have reported that GABA neurotransmission is also altered by EtOH. Since GABA modulates GH secretion by influencing the release of hypothalamic regulatory factors, and possibly through direct effects at pituitary somatotrophs, this study was designed to determine if GABAergic regulation of the hypothalamic-pituitary-GH axis is disrupted by prenatal EtOH exposure, if the effects of EtOH are sexually dimorphic, and at what developmental stages are the effects of EtOH evident. Pregnant dams were either allowed free access to standard lab chow, were provided with a 36% EtOH diet (by calories), or were pair-fed a liquid control diet isocaloric to the volume consumed by the EtOH dams. Tissue from 10, 35, and 60 day old offspring of each diet were tested in vitro in a hypothalamic-pituitary coperfusion system and were treated with the GABA agonist muscimol (M), or with M co-administered with the antagonist bicuculline (M+B). Perfusates were analyzed for GH, SRIF, and GRF content by RIA. Our findings suggest that EtOH exposure may disrupt the GH system prior to puberty, since decreased growth potential was exhibited through 35 days in EtOH . X exposed male and female offspring. A compensatory mechanism occurs after puberty, possibly involving the gonadal steroids, which rectifies these growth deficits The sensitivity of the GH system is differentially effected by EtOH during development and is gender specific. While EtOH did not inhibit muscimol-induced GH secretion in male tissues, EtOH exposure did suppress the GH and SRIF responses to bicuculline in 35 day male tissues. Unexpectedly, muscimol increased SRIF secretion from adult male and female control and EtOH tissues. Responses to the stress-induced hormonal state of pair-fed and EtOH dams were evident in female tissues, suggesting increased GABA agonistic activity due to elevated corticosterone levels or alterations in pituitary sensitivity to GRF. This study also observed direct GAB Aergic regulation of the pituitary throughout development. However, the susceptibility of this direct regulation to modulation by EtOH requires further investigation.M.S. (Master of Science