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Influence of Fetal Alcohol Exposure on the GABAergic Regulation of Growth Hormone Release in Postnatal Rats
Author(s) -
Blaine Kelly,
Gasser Kenneth,
Conway Sonya
Publication year - 1999
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1999.tb04061.x
Subject(s) - gabaergic , growth hormone , fetal growth , fetus , hormone , endocrinology , medicine , alcohol , pregnancy , physiology , biology , biochemistry , inhibitory postsynaptic potential , genetics
Background : Disruption of the growth hormone (GH) axis by maternal ethanol (ETOH) consumption may contribute to abnormalities in offspring. Interestingly, γ‐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 diet (by calories), or wcre pair‐fed an isocaloric control diet. Hypothalami and pituitarics from offspring were copcrfused, in vitro, with muscimol, a GABA A agonist, either alone or in combination with bicuculline, a GABA A antagonist. Perfusatcs werc analyzed by radioimmunoassay for GH, somatostatin (SRIF), and GH‐releasing factor (GRF). Results : Normal development of GABA regulation was evaluated first in control offspring. Sensitivity to muscimol (measured by percent increase in GH above basal levels) occurred at all ages and generally was greater in male compared to female tissue. Furthermore, the efficacy of bicuculline in depressing muscimol‐induced GH secretion increased with age in both sexes. In males, this response correlated with increased SRlF rclease. In females, releasing factor data were highly variable relative to the percent change and are not presented. Maternal ETOH consumption altered the development of GABAergic regulation of the GH axis in offspring. However, because ETOH induced changes in the response of releasing factors to muscimol appcar to offset each other, a disruption in GH release was not evident. More apparent was the reduced capacity of bicucullinc to reverse muscimol‐induced GH release from male tissue. This ETOH effect was evidcnt at 35‐days of age and was associated with reduced SRIF release. In female tissue, a reduced bicuculline response was also suggested at 35 days of age. After puberty no response was elicited by muscimol in either tissue from pair‐fed or ETOH‐exposed female offspring. Conclusion : In summary, fetal ETOH exposure influences the development of GABAergic regulation of the hypothalamic‐pituitary GH axis in an age and gender specific manner. Vulnerability of the male axis is expressed by the reduced capacity of bicucullinc to depress GH rcleasc and altered releasing factor sensitivity to GABA A ‐receptor stimulation or inhibition. There is also some suggestion that the female axis is less sensitive to bicuculline during early puberty, and, unlike the male, is insensitive to both muscimol and bicuculline after puberty. The latter, however, may be attributable to stress or nutritional deprivation, rather than to the direct effect of prenatal ETOH.