Oberbauer A M, Cruickshank J, Thomas A, Stumbaugh A, Evans K D, Murray J D, Egan A R
Department of Animal Science, University of California, Davis, USA.
Growth Dev Aging. 2001 Spring;65(1):3-13.
Exposing growing oMtla-oGH transgenic mice with the regulatable metallothionein promotor to elevated growth hormone (GH) for three weeks after weaning enhances bone length and adipocyte differentiation. The objective of the present study was to investigate the consequences of highly elevated GH exposure during fetal and early postnatal growth periods on the mature phenotype. Transgene expression, hence elevated GH, was achieved in fetuses and neonates by providing 25 mM ZnSO4 to the drinking water of the dams. Wildtype and oMtla-oGH male and female mice were a) never exposed to the transgene stimulus, b) exposed from birth to 21 d of age, c) exposed through gestation until 21 d of age, d) exposed only through gestation, or e) exposed only during the first 7 d postpartum. At 84 d of age when mature body size was reached, ulna and humerus lengths, and body, liver gonadal fat pad, mesenteric fat pad, and cleaned gastrointestinal (GI) tract weights were recorded. Bone lengths were also determined in a subset of mice at 22 d of age. While early exposure to the elevated GH increased ulna and humerus length at 22 d of age, the early GH levels failed to produce significant changes in adipose content or bone lengths at maturity. However, chronic exposure to slightly elevated GH, as seen in the transgenics never induced to express the transgenic GH, depressed liver and GI weights and increased adipose depot weights and humerus lengths across both sexes. These results suggest that certain tissues in the body, while capable of responding to GH during early developmental periods, are not fully entrained to sustain that growth response once the GH stimulus is withdrawn. Further, the preadipocyte pool appears unable to respond to GH early in development. Finally, the tissues examined exhibited a differential response to the GH suggesting that different tissues possess distinct response thresholds.
将携带可调节金属硫蛋白启动子的生长激素转基因小鼠（oMtla - oGH）在断奶后暴露于高水平生长激素（GH）三周，可增加骨长度并促进脂肪细胞分化。本研究的目的是调查在胎儿期和出生后早期生长阶段高度暴露于GH对成熟表型的影响。通过向母鼠饮用水中提供25 mM硫酸锌，在胎儿和新生儿中实现转基因表达，从而使GH水平升高。野生型和oMtla - oGH雄性和雌性小鼠分别为：a）从未暴露于转基因刺激；b）从出生到21日龄暴露；c）从妊娠期到21日龄暴露；d）仅在妊娠期暴露；或e）仅在产后前7天暴露。在达到成熟体型的84日龄时，记录尺骨和肱骨长度以及体重、肝脏、性腺脂肪垫、肠系膜脂肪垫和清洁后的胃肠道（GI）重量。还在22日龄的一部分小鼠中测定了骨长度。虽然早期暴露于升高的GH可在22日龄时增加尺骨和肱骨长度，但早期GH水平在成熟时未能在脂肪含量或骨长度上产生显著变化。然而，如在从未诱导表达转基因GH的转基因小鼠中所见，长期暴露于轻度升高的GH会降低肝脏和胃肠道重量，并增加两性的脂肪储存重量和肱骨长度。这些结果表明，身体中的某些组织虽然在早期发育阶段能够对GH作出反应，但一旦撤去GH刺激，就不能完全维持这种生长反应。此外，前脂肪细胞库在发育早期似乎无法对GH作出反应。最后，所检查的组织对GH表现出不同的反应，表明不同组织具有不同的反应阈值。
