Signaling and Signal Transduction in Endocrine Tissues
(T740) INTERMEDIN IS AN ESTROGEN-REGULATED PITUITARY PROLACTIN-RELEASING FACTOR.
Chang, Chia Lin1, Klein, Cynthia2, Hsu, Sheau Yu 2, 1 Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC2 Stanford University School of Medicine, Stanford, CA
ABSTRACT- We recently identified intermedin as a novel member of the calcitonin/CGRP peptide family and described the function as a select agonist for two of the three calcitonin receptor-like receptor (CRLR)/receptor activity-modifying protein (RAMP) receptor complexes. Of interest, analysis of intermedin expression showed that intermedin is highly expressed in both the anterior and intermediate lobes of pituitary, suggesting that intermedin could function as a paracrine factor regulating anterior pituitary hormone secretion. In support of a paracrine role of intermedin in the pituitary, we showed that intermedin treatments stimulated prolactin release from cultured pituitary cells in vitro and in vivo. In contrast, intermedin treatment decreased plasma growth hormone levels in conscious rats at 30 min following intravenous injection. Based on the finding that intermedin increases pituitary prolactin release and earlier studies showing that uncharacterized intermediate lobe-derived prolactin-releasing factors are critical for mediating suckling- and estrogen-induced prolactin release, we hypothesized that the expression of intermedin in the pituitary could be elevated during nursing in female rats and is subject to regulation by estrogens. Studies of lactating rats showed that pituitary intermedin transcripts in lactating animals increased to more than twofold of nonlactating controls whereas ovariectomy leads to a 90% reduction of intermedin expression in the pituitary. Importantly, subsequent treatment with 17 beta-estradiol or diethylstilbestrol increased the pituitary intermedin expression in ovariectomized rats, suggesting that the expression of intermedin in the pituitary is regulated by ovarian estrogens and is increased during the lactation period. Furthermore, studies of intermedin promoter luciferase reporters in transfected pituitary cells indicated that estrogens likely regulate intermedin gene expression by directly acting on the intermedin gene promoter. Collectively, the present study indicates that intermedin represents a novel estrogen-regulated pituitary prolactin-releasing factor and could play important roles in the regulation of prolactin release and other physiological processes during reproduction in females.
KEY WORDS: intermedin, prolactin, estrogen, ovary