Regulation of gastrin-releasing peptide gene expression in chickens

Abstract

Gastrin-releasing peptide (GRP) is a neuropeptide with diverse physiological functions in mammals. Similar to its mammalian counterparts, chicken GRP (cGRP) is expressed in endocrine cells of the gastrointestinal tract, including the proventriculus, where it regulates gastric acid secretion. Our previous study showed that cGRP is predominantly expressed in the anterior pituitary and acts as a novel pituitary hormone that promotes the survival of small ovarian follicles. Using primary pituitary cell cultures, we found that gonadotropin-releasing hormone 1 (GnRH1) markedly increased cGRP mRNA abundance in both dose- and time-dependent manners. Pharmacological analyses suggested that this effect likely involved the AC/cAMP/PKA pathway and the PLC/PKC/MEK/ERK pathway. We also examined the regulation of GRP expression by sex steroids. 5α-dihydrotestosterone (DHT) and progesterone (P4) downregulated GRP expression in cultured chicken pituitary cells, whereas 17β-estradiol (E2) upregulated GRP expression in dose- and time-dependent manners. Analysis of the isolated GRP 5′-flanking region identified potential estrogen receptor-binding sites, providing a molecular basis for E2-mediated upregulation of GRP expression. These findings support cGRP as a novel pituitary hormone under hypothalamic GnRH1 control and feedback regulation by sex steroids. Together with its reported role in the survival of small ovarian follicles, cGRP may contribute to the regulation of egg production in chickens.