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Department of Physiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan

(Requests for offprints should be addressed to T Nemoto; Email: taknemo{at}nms.ac.jp)

We previously demonstrated that urocortin 2 (Ucn 2) is expressed in the proopiomelanocortin (POMC) cells of rat pituitary. However, the regulatory mechanism of pituitary synthesis and secretion of Ucn 2 remained to be clarified. We hypothesized that hypothalamic hormones and glucocorticoids may control the expression and secretion of pituitary Ucn 2, as Ucn 2 is expressed in POMC-expressing cells in the pituitary. Thus, in the present study, we tested this hypothesis using primary culture of rat pituitary cells. The secretion of Ucn 2 from the anterior and intermediate pituitary cells was significantly increased by 50 mM KCl. In the anterior pituitary cells, corticotropin-releasing factor (CRF) increased mRNA expression levels and secretion of Ucn 2, although arginine vasopressin (AVP) did not induce any significant change in Ucn 2 expression or secretion. Under these conditions, both CRF and AVP increased ACTH secretion, but only CRF increased the level of POMC mRNA expression. Dexamethasone inhibited Ucn 2 and POMC mRNA expression levels, while it inhibited the secretion of only Ucn 2. In the intermediate pituitary, CRF increased both the mRNA expression levels and secretion of Ucn 2. Furthermore, dopamine did not affect either the mRNA expression level or secretion of Ucn 2 although it inhibited ß-endorphin secretion in the intermediate pituitary cells. These results suggest that the mRNA expression and secretion of Ucn 2 in POMC cells of the pituitary are positively regulated by CRF and negatively regulated by glucocorticoids.