Costrini N V, Kalkhoff R K
J Clin Invest. 1971 May;50(5):992-9. doi: 10.1172/JCI106593.
Influences of estrogen and progesterone on the development of hyperinsulinemia and augmented pancreatic islet insulin secretion during pregnancy were assessed in this study. Groups of female rats were injected subcutaneously for 21 days with varying daily dosages of estradiol benzoate or progesterone in oil. On day 21, pancreatic islets were isolated by a collagenase method. Total insulin secretion was measured after 90-min incubations of 10 islets in buffered medium containing glucose. Higher physiologic dosages of estradiol or progesterone, singly or in combination, significantly increased islet secretion above values of untreated control rats and were comparable to augmented islet responses of term, 3-wk pregnant rats. Diameter and protein content of islets obtained from steroid-treated and pregnant rats exceeded control measurements in these instances. However, 2-hr preincubations of control islets with 1 or 10 mug/ml of either steroid did not influence subsequent glucose-stimulated insulin output. In related studies, plasma insulin responses during 30 min intravenous glucose tolerance tests were significantly above control responses in term-pregnant rats and animals receiving comparable dosages of steroids for 3 wk. Unlike pregnancy or progesterone treatment, estradiol administration alone or with progesterone significantly lowered postchallenge plasma glucose concentrations. These results indicate that estradiol and progesterone contribute to enhanced islet insulin secretion and plasma insulin responses to glucose administration during pregnancy. This change is not acutely produced but can be related to hypertrophy of islets following chronic hormonal administration. Although the data do not distinguish between direct and indirect beta-cytotrophic effects of these sex steroids, metabolic actions of estradiol and progesterone may differ, since estrogen treatment lowers plasma glucose curves following the induction of hyperinsulinemia.
本研究评估了雌激素和孕酮对孕期高胰岛素血症发展及胰岛胰岛素分泌增加的影响。将雌性大鼠分组，皮下注射含不同日剂量苯甲酸雌二醇或孕酮的油剂，持续21天。在第21天，采用胶原酶法分离胰岛。将10个胰岛置于含葡萄糖的缓冲培养基中孵育90分钟后，测量总胰岛素分泌量。单独或联合使用较高生理剂量的雌二醇或孕酮，均能使胰岛分泌量显著高于未处理的对照大鼠，且与足月妊娠3周大鼠增强的胰岛反应相当。在这些情况下，从接受类固醇处理的大鼠和妊娠大鼠获得的胰岛直径和蛋白质含量超过对照测量值。然而，用1或10微克/毫升的任何一种类固醇对对照胰岛进行2小时预孵育，均不影响随后葡萄糖刺激的胰岛素分泌。在相关研究中，足月妊娠大鼠和接受3周相当剂量类固醇的动物，在30分钟静脉葡萄糖耐量试验中的血浆胰岛素反应显著高于对照反应。与妊娠或孕酮处理不同，单独给予雌二醇或与孕酮联合使用可显著降低激发后血浆葡萄糖浓度。这些结果表明，雌二醇和孕酮有助于孕期胰岛胰岛素分泌增强以及血浆胰岛素对葡萄糖给药的反应增强。这种变化不是急性产生的，而是可能与长期给予激素后胰岛肥大有关。尽管数据未区分这些性类固醇的直接和间接β细胞营养作用，但雌二醇和孕酮的代谢作用可能不同，因为雌激素处理在诱导高胰岛素血症后会降低血浆葡萄糖曲线。
