Carro E, Señarís R M, Seoane L M, Frohman L A, Arimura A, Casanueva F F, Diéguez C
Department of Physiology, Complejo Hospitalario Universitario de Santiago), University of Santiago de Compostela, Spain.
Neuroendocrinology. 1999 Jan;69(1):3-10. doi: 10.1159/000054397.
Leptin is a hormone secreted by the adipocytes that regulates food intake and energy expenditure. It is known that growth hormone (GH) secretion is markedly influenced by body weight, being suppressed in obesity and cachexia, and recent data have demonstrated that GH release is regulated by leptin levels. Although one of the sites of action of leptin is likely to be the hypothalamus, since leptin receptor mRNA is particularly abundant in several hypothalamic nuclei, the mechanisms by which leptin regulates GH secretion are not yet known. The aim of the present study was to investigate whether leptin could act at the hypothalamic level modulating somatostatin and GH-releasing hormone (GHRH) expression. The administration of anti-GHRH serum (500 microl, i.v.) completely blocked leptin-induced GH release in fasting rats. In contrast, the treatment with anti-somatostatin serum (500 microl, i.v.) significantly increased GH release in this condition. Furthermore, leptin administration (10 microg, i.c.v.) to intact fasting animals reversed the inhibitory effect produced by fasting on GHRH mRNA levels in the arcuate nucleus of the hypothalamus, and increased somatostatin mRNA content in the periventricular nucleus. Finally, leptin administration (10 microgram, i.c.v.) to hypophysectomized fasting rats increased GHRH mRNA levels, and decreased somatostatin mRNA content, indicating an effect of leptin on hypothalamic GHRH- and somatostatin-producing neurons. These findings suggest a role for GHRH and somatostatin as mediators of leptin-induced GH secretion.
瘦素是一种由脂肪细胞分泌的激素，可调节食物摄入和能量消耗。已知生长激素（GH）的分泌受体重显著影响，在肥胖和恶病质状态下受到抑制，并且最近的数据表明GH的释放受瘦素水平调节。尽管瘦素的作用位点之一可能是下丘脑，因为瘦素受体mRNA在下丘脑的几个核中特别丰富，但瘦素调节GH分泌的机制尚不清楚。本研究的目的是调查瘦素是否能在下丘脑水平发挥作用，调节生长抑素和生长激素释放激素（GHRH）的表达。静脉注射抗GHRH血清（500微升）可完全阻断禁食大鼠中瘦素诱导的GH释放。相反，在这种情况下，静脉注射抗生长抑素血清（500微升）治疗可显著增加GH释放。此外，向完整的禁食动物脑室内注射瘦素（10微克）可逆转禁食对下丘脑弓状核中GHRH mRNA水平产生的抑制作用，并增加室旁核中生长抑素mRNA的含量。最后，向垂体切除的禁食大鼠脑室内注射瘦素（10微克）可增加GHRH mRNA水平，并降低生长抑素mRNA含量，表明瘦素对下丘脑产生GHRH和生长抑素的神经元有作用。这些发现提示GHRH和生长抑素作为瘦素诱导GH分泌的介质发挥作用。
