Somatostatin-stimulated growth hormone-releasing factor secretion in vitro is modified by fetal ethanol exposure.
Exposure to ethanol (ETOH) in utero has been found to alter the growth hormone (GH)/insulin-like growth factor axis and retard growth. GH release is regulated by the interaction of the hypothalamic hormones somatostatin [somatotropin release inhibiting factor (SRIF)] and GH-releasing factor (GRF). Communication between these factors occurs at both the hypothalamic and pituitary levels. In this study, we examined the effect of fetal ETOH exposure on the postnatal development of SRIF regulation of GRF release at the hypothalamic level. The studies were conducted on hypothalami from 30- and 60-day-old pups in an in vitro perfusion system. SRIF was tested against K(+)-induced GRF release. Basal GRF release, not in the presence of external stimuli, from the hypothalami of ETOH-exposed pups (both male and female) was greater than GRF release from tissue of offspring of both pair-fed and control dams. GRF release was also greater in female, compared with male hypothalami, and the effect of ETOH was more pronounced at 30, compared with 60, days of age. The heightened release of GRF may reflect reduced sensitivity to feedback regulation by GH in ETOH-exposed pups. Furthermore, fetal ETOH exposure reversed the effect of SRIF modulation on K(+)-induced GRF release. In hypothalami from offspring of both pair-fed (except 30-day-old females) and ad libitum-fed controls, SRIF enhanced the K(+)-induced GRF release. In tissue from ETOH-exposed pups (except 60-day-old males), GRF release was inhibited by SRIF. We suggest that this pattern may reflect a change in the characteristics of SRIF connections with GRF neurons by ETOH. In summary, this data indicates that both basal and SRIF-stimulated GRF is altered by ETOH and that effect remains significantly altered at least until puberty.
Conway
S
S
Biology Department, Northern Illinois University, DeKalb 60115, USA.
Swain
R
R
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology*
D000431:Ethanol; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone; D011188:Potassium