Santana P, Akana S F, Hanson E S, Strack A M, Sebastian R J, Dallman M F
Department of Physiology, University of California San Francisco 94143-044, USA.
Endocrinology. 1995 May;136(5):2214-22. doi: 10.1210/endo.136.5.7720670.
Corticosteroids stimulate and insulin inhibits energy acquisition (food intake); conversely, corticosteroids inhibit and insulin stimulates energy storage (body weight gain). Thus, together these hormones mediate long-term energy balance. This study tested whether the stimulatory action of corticosteroids on food intake was mediated by association with high affinity mineralocorticoid receptors (MRs) or lower affinity glucocorticoid receptors (GRs). Young male rats were adrenalectomized (ADX) and given vehicle (control) or streptozotocin (diabetic); subgroups of rats were infused with vehicle, aldosterone (Aldo, an MR agonist in vivo), dexamethasone (Dex, a GR agonist in vivo), or Aldo&Dex for the 5 days after ADX. Sham-ADX rats were included. Food intake, body weight gain, and epididymal white adipose and interscapular brown adipose tissue stores were weighed. ADX decreased food intake by approximately 24%, and food intake was not increased by diabetes as it was in sham-ADX rats. In control ADX rats, Dex, but not Aldo, stimulated insulin, and food intake was not significantly affected by either hormone; together, Aldo and Dex restored insulin and food intake to sham-ADX rats. Food intake in diabetic ADX rats was significantly increased by each treatment (ADX < Aldo < Dex < Aldo&Dex = sham). Aldo increased body weight through an increase in fluid volume (estimated by decreased plasma protein concentration); however, fat stores were not different from ADX. Dex reduced body weight in control rats but maintained fat stores; in diabetic rats, body weight and fat stores were less than or similar to ADX. We conclude that: 1) corticosteroids, acting through association with both MRs and GRs, stimulate food intake; 2) insulin counteracts the GR-mediated stimulation of food intake in control rats; and 3) Dex and insulin, which is stimulated by Dex, selectively maintain or increase body fat stores, probably at the expense of protein stores.
皮质类固醇刺激而胰岛素抑制能量获取（食物摄入）；相反，皮质类固醇抑制而胰岛素刺激能量储存（体重增加）。因此，这些激素共同调节长期能量平衡。本研究测试了皮质类固醇对食物摄入的刺激作用是否通过与高亲和力盐皮质激素受体（MRs）或低亲和力糖皮质激素受体（GRs）结合来介导。对年轻雄性大鼠进行肾上腺切除术（ADX），并给予溶剂（对照）或链脲佐菌素（糖尿病组）；在ADX后的5天内，给大鼠亚组注入溶剂、醛固酮（Aldo，体内MR激动剂）、地塞米松（Dex，体内GR激动剂）或Aldo&Dex。纳入假手术ADX大鼠。称量食物摄入量、体重增加量以及附睾白色脂肪和肩胛间棕色脂肪组织储存量。ADX使食物摄入量减少约24%，糖尿病组的食物摄入量未像假手术ADX大鼠那样增加。在对照ADX大鼠中，Dex而非Aldo刺激胰岛素分泌，两种激素对食物摄入量均无显著影响；Aldo和Dex共同作用可使胰岛素和食物摄入量恢复至假手术ADX大鼠水平。每种处理均显著增加了糖尿病ADX大鼠的食物摄入量（ADX＜Aldo＜Dex＜Aldo&Dex = 假手术组）。Aldo通过增加液体量（通过血浆蛋白浓度降低来估计）使体重增加；然而，脂肪储存量与ADX组无差异。Dex使对照大鼠体重减轻但维持脂肪储存量；在糖尿病大鼠中，体重和脂肪储存量低于或类似于ADX组。我们得出以下结论：1）皮质类固醇通过与MRs和GRs结合发挥作用，刺激食物摄入；2）胰岛素抵消了对照大鼠中GR介导的食物摄入刺激作用；3）Dex和由Dex刺激产生的胰岛素选择性地维持或增加体脂储存，可能是以蛋白质储存为代价。
