Novel action of pituitary urocortin 2 in the regulation of expression and secretion of gonadotropins.
Urocortins 2 (Ucn 2), one of the 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 short interfering RNA against CRF-R2, and anti-Ucn 2 rabbit IgG increased the secretion and mRNA expression of gonadotropins. intraperitoneal 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 i.p. injection of anti-Ucn 2 IgG into immature female rats induced a tendency toward earlier occurrence of menarche compared with 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.
Nemoto
Takahiro
T
Department of Physiology, Nippon Medical School, Tokyo, Japan. taknemo@nms.ac.jp
Yamauchi
Naoko
N
Shibasaki
Tamotsu
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006065:Gonadotropins, Pituitary / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D008572:Menarche / Q000187:drug effects / Q000235:genetics; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D055571:Secretory Pathway / Q000187:drug effects / Q000235:genetics; D054832:Urocortins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D000906:Antibodies; D006065:Gonadotropins, Pituitary; D006727:Hormone Antagonists; D034741:RNA, Small Interfering; D054832:Urocortins