Danilovich N, Wernsing D, Coschigano K T, Kopchick J J, Bartke A
Department of Physiology, Southern Illinois University, Carbondale 62901-6512, USA.
Endocrinology. 1999 Jun;140(6):2637-40. doi: 10.1210/endo.140.6.6992.
Mice homozygous for targeted disruption of the GH receptor/GH binding protein gene (GH-R-KO mice; -/-) exhibit reduced plasma IGF-I levels, elevated plasma GH levels, and dwarf phenotype. Although most GH-R-KO mice are fertile, age at first conception is greatly delayed in -/- x -/- matings. Here we report that the age of vaginal opening is significantly delayed in GH-R-KO vs. normal mice, but it can be advanced by treatment with recombinant human (rh)IGF-I. In pregnant GH-R-KO females, fetal size is reduced and pregnancy is prolonged while placental weight is, unexpectedly, increased. Alterations in fetal and placental weight are related to maternal rather than fetal genotype. Moreover, litter size and body weight of newborn pups are significantly reduced in GH-R-KO vs. normal females. Reduction in litter size reflects both dam and sire effects. We conclude that GH resistance and consequent reduction in peripheral IGF-I levels is associated with delay of female puberty, alterations in fetal and placental growth, delay of parturition, and reduced litter size.
生长激素受体/生长激素结合蛋白基因靶向破坏的纯合子小鼠（GH-R-KO小鼠；-/-）表现出血浆胰岛素样生长因子-I（IGF-I）水平降低、血浆生长激素水平升高和侏儒表型。虽然大多数GH-R-KO小鼠可育，但在-/-×-/-交配中首次受孕的年龄会大大延迟。在此我们报告，与正常小鼠相比，GH-R-KO小鼠的阴道开口年龄显著延迟，但用重组人（rh）IGF-I治疗可使其提前。在怀孕的GH-R-KO雌性小鼠中，胎儿大小减小，孕期延长，而胎盘重量却意外增加。胎儿和胎盘重量的改变与母体而非胎儿基因型有关。此外，与正常雌性相比，GH-R-KO雌性小鼠的窝仔数和新生幼崽体重显著降低。窝仔数减少反映了母本和父本的影响。我们得出结论，生长激素抵抗以及随之而来的外周IGF-I水平降低与雌性青春期延迟、胎儿和胎盘生长改变、分娩延迟以及窝仔数减少有关。
