Sex-Related Differences in Chromogranin A, Chromogranin B and Secretogranin II Gene Expression in Rat Pituitary

Chromogranin A, an acidic secretory protein, is widely distributed throughout diverse endocrine cells and the central and peripheral nervous systems. Chromogranin A is co-stored and co-secreted from secretory vesicles together with the endogenous hormones or neurotransmitters. Recently, two peptides derived from the Chromogranin A precursor have been shown to inhibit secretion from endocrine cells. In the present study, we investigated the regulation of the biosynthesis of Chromogranin A by estrogen in various tissues. In the pituitary, steady-state levels of Chromogranin A mRNA were markedly reduced by 64% in estrogen-treated male rats. At the protein level, a comparable decrease was found. Chromogranin B and secretogranin II, two other secretory proteins co-stored with Chromogranin A, were slightly increased by estrogen. In pituitaries of female rats Chromogranin A mRNA and protein levels were significantly lower than in males. For Chromogranin B on the other hand, a 2-fold increase of mRNA levels was found. Our observations demonstrate that physiologic concentrations of estrogen strongly affect Chromogranin A levels in the pituitary resulting in a sex-related difference in Chromogranin A gene expression. Based on these and previous results demonstrating increased biosynthesis of Chromogranin A by glucocorticoids and calciferol, we suggest that a typical and characteristic feature of the Chromogranin A gene is its regulation by at least three different classes of steroid hormones.