Influence of fetal alcohol exposure on the GABAergic regulation of growth hormone release in postnatal rats

Background: Disruption of the growth hormone (GH) axis by maternal ethanol (ETOH) consumption may contribute to abnormalities in offspring. Interestin gly, gamma-aminobutyric acid (GABA) neurotransmission, which is vulnerable to fetal ETOH exposure, also regulates the hypothalamic-pituitary GH axis. This study examines whether GABAergic control of this axis is disrupted by prenatal ETOH exposure. Methods: Pregnant dams were fed either rat chow ad libitum or a 36% ETOH di et (by calories), or were pair-fed an isocaloric control diet. Hypothalami and pituitaries from offspring were coperfused, in vitro, with muscimol, a GABA(A) agonist, either alone or in combination with bicuculline, a GABA, a ntagonist. Perfusates were analyzed by radioimmunoassay for GH, somatostati n (SRIF), and GH-releasing factor (GRF). Results: Normal development of GABA regulation was evaluated first in contr ol offspring. Sensitivity to muscimol (measured by percent increase in GH a bove basal levels) occurred at all ages and generally was seater in male co mpared to female tissue. Furthermore, the efficacy of bicuculline in depres sing muscimol-induced GH secretion increased with age in both sexes. In mal es, this response correlated with increased SRIF release. In females, relea sing factor data were highly variable relative to the percent change and ar e not presented. Maternal ETOH consumption altered the development of GABAergic regulation o f the GH axis in offspring. However, because ETOH induced changes in the re sponse of releasing factors to muscimol appear to offset each other, a disr uption in GH release was not evident. More apparent was the reduced capacit y of bicuculline to reverse muscimol-induced GH release from male tissue. T his ETOH effect was evident at 35-days of age and was associated with reduc ed SRIF release. In female tissue, a reduced bicuculline response was also suggested at 35 days of age. After puberty no response was elicited by musc imol in either tissue from pair-fed or ETOH-exposed female offspring. Conclusion: In summary, fetal ETOH exposure influences the development of G ABAergic regulation of the hypothalamic-pituitary GH aids in an age and gen der specific manner. Vulnerability of the male axis is expressed by the red uced capacity of bicuculline to depress GH release and altered releasing fa ctor sensitivity to GABA(A)-receptor stimulation or inhibition. There is al so some suggestion that the female axis is less sensitive to bicuculline du ring early puberty, and, unlike the male, is insensitive to both muscimol a nd bicuculline after puberty, The latter, however, may be attributable to s tress or nutritional deprivation, rather than to the direct effect of prena tal ETOH.