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.