Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Advocate Aurora Research Institute, Milwaukee, WI, USA.
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Physiol Rep. 2021 Jan;9(1):e14663. doi: 10.14814/phy2.14663.
Hypoxia is common with preterm birth and may lead to long-term effects on adult pancreatic endocrine function and insulin sensitivity. This phenomenon may be sexually dimorphic due to the hypoxia-induced augmentation of the neonatal androgen surge in male newborns. We evaluated this phenomenon by pretreating neonatal rats on postnatal days (PD) 1, 6, 13, or 20 with flutamide (a nonsteroidal androgen receptor antagonist) at a standard or a high dose (10 or 50 mg/kg) compared to vehicle control. One day later, neonatal rats were exposed to either acute normoxic or hypoxic separation (fasting) for 90 min, and blood was sampled for the measurement of insulin and glucose and the calculation of HOMA-IR as an index of insulin resistance. During normoxic and hypoxic separation (fasting), flutamide increased insulin secretion in PD2, PD7, and PD14 pups, high dose flutamide attenuated insulin secretion, and high dose flutamide attenuated the increase in HOMA-IR due to hypoxia. Our studies suggest a unique role of the androgen receptor in the control of neonatal pancreatic function, possibly by blocking a direct effect of neonatal testosterone or in response to indirect regulatory effects of androgens on insulin sensitivity.
缺氧在早产儿中很常见，可能导致成年后胰腺内分泌功能和胰岛素敏感性的长期影响。这种现象可能具有性别二态性，因为缺氧会增加雄性新生儿的新生雄激素激增。我们通过在出生后第 1、6、13 或 20 天用氟他胺（一种非甾体雄激素受体拮抗剂）预处理新生大鼠，用标准剂量（10 或 50mg/kg）或高剂量（10 或 50mg/kg）与载体对照进行预处理来评估这种现象。一天后，新生大鼠暴露于急性常氧或缺氧分离（禁食）90 分钟，采集血液用于测量胰岛素和葡萄糖，并计算 HOMA-IR 作为胰岛素抵抗的指标。在常氧和缺氧分离（禁食）期间，氟他胺增加了 PD2、PD7 和 PD14 幼鼠的胰岛素分泌，高剂量氟他胺减弱了胰岛素分泌，高剂量氟他胺减弱了缺氧引起的 HOMA-IR 增加。我们的研究表明雄激素受体在控制新生儿胰腺功能方面具有独特的作用，可能是通过阻断新生儿睾酮的直接作用，或对胰岛素敏感性的雄激素的间接调节作用。
