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Cocaine- and Amphetamine-Regulated Transcript Peptide in the Rat Anterior Pituitary Gland Is Localized in Gonadotrophs and Suppresses Prolactin Secretion

Division of Diabetes and Endocrinology (G.K., K.T.), Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan; Department of Pathology (S.T., R.Y.O.), Tokai University School of Medicine, Kanagawa 259-1193, Japan; Division of the Science of Nursing (Y.N.), College of Medical Technology, Kyoto University, Kyoto 606-8507, Japan; and Yerkes Regional Primate Research Center of Emory University (M.J.K.), Atlanta, Georgia 30329

Address all correspondence and requests for reprints to: Robert Yoshiyuki Osamura, M.D., Ph.D., Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. E-mail: osamura{at}is.icc.u-tokai.ac.jp.

Cocaine- and amphetamine-regulated transcript (CART) mRNA and CART peptide are abundant in the hypothalamic nuclei that control anterior pituitary function. CART peptide has also been localized in the anterior pituitary gland itself, although its role in pituitary function has not as yet been elucidated.

In the present study, we investigated the localization and function of CART peptide in the anterior pituitary gland. Immunohistochemical observations revealed that CART peptide colocalized with FSH and LH in gonadotroph cells but that it was absent from the other hormone-producing cells. Immunoelectronmicroscopy suggested that CART peptide and gonadotropin were colocalized in the same secretory granules. CART peptide suppressed prolactin release from dispersed anterior pituitary cells 15 min after its addition into the media [basal production, 234.9 ± 14.6 ng/ml vs. CART 55–102 peptide 100 nM, 125.0 ± 18.2 ng/ml (P < 0.01, n = 5)]. Prolactin release was suppressed by CART in a dose-related manner; on the other hand, CART peptide did not affect the secretion of other anterior pituitary hormones. CART peptide synthesis by these cells was elevated 15 min after the addition of leptin to the media (100 nM), as determined by immunoblotting, but LHRH (10 nM) did not significantly affect CART peptide expression.

These findings suggest that CART synthesis in the anterior pituitary may be stimulated by leptin and that CART peptide may play a role in the regulation of anterior pituitary hormone secretion in the rat.

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