title: Influence of fetal alcohol exposure on the GABAergic regulation of growth hormone release in postnatal rats.
abstract: BACKGROUND
  Disruption of the growth hormone (GH) axis by maternal ethanol (ETOH) consumption may contribute to abnormalities in offspring. Interestingly, 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 diet (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) antagonist. Perfusates were 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 SRIF release. 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. flowever, because ETOH induced changes in the response of releasing factors to muscimol appear to offset each other, a disruption in GH release was not evident. More apparent was the reduced capacity of bicuculline to reverse muscimol-induced GH release from male tissue. This ETOH effect was evident 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.
  
  
  CONCLUSIONS
  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 bicuculline to depress GH release 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.
authors.affiliation: Department of Biological Sciences, Northern Illinois University, Dekalb 60115, USA.
authors.forename: K
authors.initials: K
authors.lastname: Blaine
authors.forename: K
authors.initials: K
authors.lastname: Gasser
authors.forename: S
authors.initials: S
authors.lastname: Conway
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects*; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D013006:Growth Hormone / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012737:Sex Factors; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D013006:Growth Hormone; D001640:Bicuculline