Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio.
Am J Physiol Endocrinol Metab. 2019 Nov 1;317(5):E925-E940. doi: 10.1152/ajpendo.00229.2019. Epub 2019 Sep 3.
The maternal organism undergoes numerous metabolic adaptations to become prepared for the demands associated with the coming offspring. These metabolic adaptations involve changes induced by several hormones that act at multiple levels, ultimately influencing energy and glucose homeostasis during pregnancy and lactation. Previous studies have shown that central growth hormone (GH) action modulates glucose and energy homeostasis. However, whether central GH action regulates metabolism during pregnancy and lactation is still unknown. In the present study, we generated mice carrying ablation of GH receptor (GHR) in agouti-related protein (AgRP)-expressing neurons, in leptin receptor (LepR)-expressing cells or in the entire brain to investigate the role played by central GH action during pregnancy and lactation. AgRP-specific GHR ablation led to minor metabolic changes during pregnancy and lactation. However, while brain-specific GHR ablation reduced food intake and body adiposity during gestation, LepR GHR knockout (KO) mice exhibited increased leptin responsiveness in the ventromedial nucleus of the hypothalamus during late pregnancy, although their offspring showed reduced growth rate. Additionally, both Brain GHR KO and LepR GHR KO mice had lower glucose tolerance and glucose-stimulated insulin secretion during pregnancy, despite presenting increased insulin sensitivity, compared with control pregnant animals. Our findings revealed that during pregnancy central GH action regulates food intake, fat retention, as well as the sensitivity to insulin and leptin in a cell-specific manner. Together, the results suggest that GH acts in concert with other "gestational hormones" to prepare the maternal organism for the metabolic demands of the offspring.
母体组织经历了许多代谢适应，以准备好应对即将到来的后代的需求。这些代谢适应涉及到几种激素在多个层面上诱导的变化，最终影响妊娠和哺乳期的能量和葡萄糖稳态。以前的研究表明，中枢生长激素（GH）的作用调节葡萄糖和能量稳态。然而，中枢 GH 作用是否在妊娠和哺乳期调节代谢仍不清楚。在本研究中，我们生成了在 AgRP 表达神经元、瘦素受体（LepR）表达细胞或整个大脑中敲除 GH 受体（GHR）的小鼠，以研究中枢 GH 作用在妊娠和哺乳期的作用。AgRP 特异性 GHR 敲除导致妊娠和哺乳期的代谢变化较小。然而，虽然脑特异性 GHR 敲除减少了妊娠期间的食物摄入和体脂肪堆积，但 LepR GHR 敲除（KO）小鼠在妊娠晚期下丘脑腹内侧核表现出增加的瘦素反应性，尽管它们的后代生长速度较慢。此外，与对照妊娠动物相比，脑 GHR KO 和 LepR GHR KO 小鼠在妊娠期间的葡萄糖耐量和葡萄糖刺激的胰岛素分泌较低，尽管表现出更高的胰岛素敏感性。我们的研究结果表明，在妊娠期间，中枢 GH 作用以细胞特异性的方式调节食物摄入、脂肪保留以及对胰岛素和瘦素的敏感性。总之，这些结果表明 GH 与其他“妊娠激素”一起作用，为母体组织准备应对后代的代谢需求。
