Conway S, Garbouzova Y
Biology Department, Northern Illinois University, DeKalb 60115, USA.
Alcohol Clin Exp Res. 1996 Oct;20(7):1212-20. doi: 10.1111/j.1530-0277.1996.tb01115.x.
This study examines the influence of fetal ethanol (ETOH) exposure and pair-feeding dams on postnatal, releasing factor-induced pituitary growth hormone (GH) release and adenosine 3',5'-cyclic phosphate (cAMP) accumulation. Fetuses were exposed to ETOH in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Postnatal body weights were measured at sacrifice to evaluate the influence of ETOH on growth. Pituitary weight and protein content were measured to determine if changes in GH secretion or cAMP are proportional to the overall effect of ETOH on the pituitary. Pituitaries from 1-, 10-, and 60-day-old pups were explanted and incubated without hormones or with either somatostatin [somatotropin-release inhibiting factor (SRIF); 10(-9) M], or GH-releasing factor (GRF; 5 x 10(-9) M). Radioimmunoassays were used to determine tissue cAMP content, after extraction, and media GH concentration. Results indicate that fetal ETOH exposure specifically reduces the weight of both male and female pups. However, by 60 days of age, this reduction is not different from that found in pups of pair-fed controls, and both groups weighed less than pups of ad libitum controls. Furthermore, both pituitary weight and protein content were proportionately reduced in ETOH-exposed pups. In regard to releasing factor sensitivity, compared with pituitaries from ad libitum controls, the capacity of GRF to simulate GH release was diminished in 10-day-old males (p < 0.006) exposed to ETOH. On the other hand, the capacity of GRF to stimulate cAMP accumulation was generally enhanced by prenatal ETOH exposure. The capacity of SRIF to depress GH release was diminished in ETOH pups, compared with both pair-fed and ad libitum-fed controls (p < 0.0001). This difference in GH release was more apparent in pituitaries from females than males (p < 0.001). However, the depressed SRIF response was not associated with altered cAMP accumulation. These data suggest that fetal ETOH exposure has a sexually dimorphic effect on pituitary sensitivity to GH-releasing factors that may be related to altered regulation of GH release and susceptibility to growth retardation.
本研究考察了胎儿酒精（ETOH）暴露及对母鼠配对饲养对产后释放因子诱导的垂体生长激素（GH）释放和腺苷3',5'-环磷酸（cAMP）积累的影响。通过给母鼠喂食含36%（热量来源于ETOH：6.6% v/v）的ETOH液体饮食，使胎儿在子宫内暴露于ETOH。在处死时测量产后体重，以评估ETOH对生长的影响。测量垂体重量和蛋白质含量，以确定GH分泌或cAMP的变化是否与ETOH对垂体的总体影响成比例。将1日龄、10日龄和60日龄幼崽的垂体取出，在无激素的情况下孵育，或与生长抑素[促生长激素释放抑制因子（SRIF）；10(-9) M]或生长激素释放因子（GRF；5×10(-9) M）一起孵育。提取后，采用放射免疫分析法测定组织cAMP含量和培养基中GH浓度。结果表明，胎儿ETOH暴露会特异性降低雄性和雌性幼崽的体重。然而，到60日龄时，这种体重降低与配对饲养对照组幼崽的情况并无差异，且两组体重均低于自由采食对照组幼崽。此外，暴露于ETOH的幼崽垂体重量和蛋白质含量均相应降低。关于释放因子敏感性，与自由采食对照组的垂体相比，暴露于ETOH的10日龄雄性幼崽中，GRF模拟GH释放的能力降低（p < 0.006）。另一方面，产前ETOH暴露通常会增强GRF刺激cAMP积累的能力。与配对饲养和自由采食对照组相比，ETOH幼崽中SRIF抑制GH释放的能力降低（p < 0.0001）。这种GH释放的差异在雌性垂体中比雄性更明显（p < 0.001）。然而，SRIF反应降低与cAMP积累改变无关。这些数据表明，胎儿ETOH暴露对垂体对GH释放因子的敏感性具有性别差异效应，这可能与GH释放调节改变和生长迟缓易感性有关。
