Hill D J, Riley S C, Bassett N S, Waters M J
Lawson Research Institute, St. Joseph's Health Centre, London, Ontario, Canada.
J Clin Endocrinol Metab. 1992 Aug;75(2):646-50. doi: 10.1210/jcem.75.2.1379261.
Pituitary GH secretion appears largely unnecessary for the attainment of normal birth size in many species, including man. This is believed to be due to an immaturity and/or an absence of GH receptors in many fetal tissues. However, in vitro studies using late first trimester human fetal tissues have demonstrated mitogenic actions of GH on liver and stimulation of insulin biosynthesis in pancreas. To resolve this discrepancy, we have employed immunocytochemistry to identify the presence and distribution of GH receptors in various human fetal tissues. Fetuses of 14-16 weeks gestation were obtained after therapeutic abortion, tissues were fixed, and immunocytochemistry was performed using monoclonal antibodies against purified rat or rabbit GH receptor. The specificity of staining was confirmed by preabsorption of the antibodies with 1) adult rat liver membranes or 2) human fetal liver membranes, both of which possess specific GH-binding sites, or 3) human fetal skeletal muscle membranes, which do not specifically bind GH. Positive staining was seen in a subpopulation of liver parenchymal cells, in the ductal and endocrine tissue of pancreas, in the germinal layer of the epidermis and the deeper dermal layers of skin, and in the tubular epithelium of kidney. No immunopositive staining was seen in skeletal or cardiac muscle, epiphyseal growth plate, lung, intestine, or adrenal. Positive staining was present in the neuronal cell bodies of the cerebral cortex. GH receptor was also detectable as early as 8 weeks gestation in syncytial layers of the placenta and was maintained until term. Results demonstrate the presence of immunoreactive GH receptor/binding protein in some human fetal tissues early in development. In particular, these results would support a role for GH in the growth and function of liver and pancreas.
在包括人类在内的许多物种中,垂体生长激素(GH)的分泌对于达到正常出生体重似乎并非必不可少。据信这是由于许多胎儿组织中生长激素受体不成熟和/或缺乏。然而,使用妊娠早期末人类胎儿组织进行的体外研究表明,生长激素对肝脏有促有丝分裂作用,并能刺激胰腺中的胰岛素生物合成。为了解决这一差异,我们采用免疫细胞化学方法来确定生长激素受体在各种人类胎儿组织中的存在和分布。治疗性流产后获得妊娠14 - 16周的胎儿,组织固定后,使用针对纯化大鼠或兔生长激素受体的单克隆抗体进行免疫细胞化学检测。通过用以下物质预吸收抗体来确认染色的特异性:1)成年大鼠肝细胞膜;2)人类胎儿肝细胞膜,二者均具有特异性生长激素结合位点;3)人类胎儿骨骼肌细胞膜,其不特异性结合生长激素。在肝实质细胞亚群、胰腺的导管和内分泌组织、表皮生发层和皮肤深层真皮层以及肾的肾小管上皮中可见阳性染色。在骨骼肌、心肌、骨骺生长板、肺、肠或肾上腺中未见免疫阳性染色。大脑皮质的神经元细胞体中有阳性染色。早在妊娠8周时,在胎盘的合体层中就可检测到生长激素受体,并且一直维持到足月。结果表明在发育早期一些人类胎儿组织中存在免疫反应性生长激素受体/结合蛋白。特别是,这些结果将支持生长激素在肝脏和胰腺的生长及功能中发挥作用。