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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0467v1 201/1/105    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nemoto, T. Articles by Shibasaki, T. Search for Related Content PubMed PubMed Citation Articles by Nemoto, T. Articles by Shibasaki, T.

T Nemoto, Physiology, Nippon Medical School, Tokyo, 113-8602, Japan
N Yamauchi, Physiology, Nippon Medical School, Tokyo, Japan
T Shibasaki, Physiology, Nippon Medical School, Tokyo, Japan

Correspondence: Takahiro Nemoto, Email: taknemo{at}nms.ac.jp

Abstract

Urocortins 2 (Ucn 2), one of corticotropin releasing factor (CRF) peptide family, is thought to be an endogenous ligand for CRF type 2 receptor (CRF-R2). We previously demonstrated that Ucn 2 is expressed in the corticotrophs of rat pituitary, and the mRNA expression and secretion of Ucn 2 in corticotrophs of rat anterior pituitary are regulated by CRF and glucocorticoids. Since CRF-R2 has been reported to be expressed on gonadotrophs of the rat pituitary, we hypothesized that pituitary Ucn 2 may control the expression and secretion of gonadotropins. Monolayer culture of rat anterior pituitary cells showed that the secretion of gonadotropins was suppressed by Ucn 2. A CRF-R2 selective antagonist, adenoviral-mediated expression of siRNA against CRF-R2, and anti-Ucn 2 rabbit IgG increased the secretion and mRNA expression of gonadotropins. Intraperitoneal (ip) injection of anti-Ucn 2 IgG into immature male rats significantly increased the secretion and mRNA expression of gonadotropins compared with those in normal rabbit IgG-injected rats. Daily ip injection of anti-Ucn 2 IgG into immature female rat induced a tendency toward earlier occurrence of menarche compared to normal rabbit IgG-injected rats. These findings suggest that pituitary Ucn 2 is involved in the regulatory mechanism of the expression and secretion of gonadotropins through its tonic and inhibitory action on gonadotrophs in a paracrine manner.