Differential expression and function of beacon in the rat adrenal cortex and medulla

Abstract

Beacon gene is overexpressed in obese rats, and beacon was found to stimulate food intake. Evidence has been recently provided that beacon is also expressed in the endocrine glands of normal rats, including adrenal cortex, of which it appears to regulate secretory activity. To further characterize the role of beacon in the rat adrenals, we investigated the level of beacon expression in the adrenal zona glomerulosa (ZG), zona fasciculata-reticularis (ZF/R) and medulla (AM), and the in vitro secretory responses to beacon[47-73] (hereinafter, beacon) of adrenocortical and adrenomedullary tissues. Real-time polymerase chain reaction revealed similar high levels of beacon mRNA in the ZG and ZF/R, and significantly lower (-80%) levels in AM. Immunocytochemistry showed that the distribution of beacon protein followed that of beacon mRNA. Quantitative high pressure liquid chromatography demonstrated that beacon (5x10(-7) M) reduced by about 56% the in vitro total steroid-hormone production from ZG and ZF/R tissues, without affecting catecholamine secretion from AM specimens. The beacon-induced lowering in the secretory activity of adrenal cortex depended on similar reductions (from 50-64%) in the production of the main adrenocortical hormones (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxy-corticosterone and aldosterone), thereby suggesting an inhibitory action of beacon in the early step of steroidogenesis (i.e. the conversion of cholesterol to pregnenolone). The hypothesis is advanced that beacon is to be considered an autocrine-paracrine negative regulator of mineralo- and glucocorticoid synthesis in the rat adrenal gland.