Tempel D L, Leibowitz S F
Rockefeller University, New York, New York 10021.
J Neuroendocrinol. 1994 Oct;6(5):479-501. doi: 10.1111/j.1365-2826.1994.tb00611.x.
The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle. Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 microgram %) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-10 micrograms %) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further (> 10 micrograms %) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle. Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term.(ABSTRACT TRUNCATED AT 400 WORDS)
糖皮质激素皮质酮（CORT）被认为在调节营养摄入和代谢方面具有重要作用。本综述中描述的最新证据表明，这种肾上腺激素的作用是通过两种类固醇受体亚型介导的，即I型盐皮质激素受体和II型糖皮质激素受体。这些受体对CORT具有不同的亲和力，对循环激素的不同水平做出反应。它们介导类固醇的不同作用，这可以通过摄入的特定营养素和昼夜节律周期的特定阶段来区分。在正常生理条件下，I型受体持续被激活，要么是通过昼夜节律周期中通常可获得的低基础水平循环CORT（0.5 - 2微克%），要么可能是通过盐皮质激素醛固酮。这种I型激活对于维持进食周期中大多数餐食期间发生的脂肪摄入和脂肪沉积是必需的。相比之下，II型受体在昼夜高峰期间通常达到的中等水平CORT（2 - 10微克%）的阶段性激活下被激活。这种受体的激活对于碳水化合物摄入和代谢的自然激增是必需的，这在活跃进食周期开始时至关重要，此时身体的糖原储备处于最低点，需要糖异生来维持血糖水平。在能量需求增加的时期，如运动和食物限制后，当CORT水平进一步升高（>10微克%）且其对脂肪和蛋白质储备的分解代谢作用占主导以提供额外的底物用于葡萄糖稳态时，该受体也会被激活。CORT对脂肪和碳水化合物平衡的这些作用部分是由位于下丘脑室旁核内的I型和II型受体介导的，已知该核在控制营养摄入、代谢以及循环CORT水平方面具有关键作用。此外，该核内的II型受体，除了弓状核外，可能与肽神经肽Y和儿茶酚胺去甲肾上腺素产生正向相互作用，这两者在自然进食周期开始时都起到增强自然碳水化合物进食和CORT释放的作用。因此，在正常情况下，内源性CORT通过I型和II型类固醇受体系统的协同作用，在控制自然昼夜节律周期中的营养摄入和代谢方面具有主要功能。通过这种作用，CORT长期对总热量摄入和体重增加产生影响。（摘要截取自400字）
