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Am J Physiol Endocrinol Metab 287: E583-E590, 2004. First published May 11, 2004; doi:10.1152/ajpendo.00576.2003
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Regulation of rat pituitary cocaine- and amphetamine-regulated transcript (CART) by CRH and glucocorticoids

S. A. Stanley,1,* K. G. Murphy,1,* G. A. Bewick,1,* W. M. Kong,1 J. Opacka-Juffry,2 J. V. Gardiner,1 M. Ghatei,1 C. J. Small,1 and S. R. Bloom1

1Endocrine Unit, Faculty of Medicine, ICSTM, Hammersmith Hospital, London, W12 0NN; and 2School of Life and Sport Sciences, Whitelands College, University of Surrey, Roehampton, London SW15 3SN, United Kingdom

Submitted 17 December 2003 ; accepted in final form 6 May 2004

Cocaine- and amphetamine-regulated transcript (CART) was originally isolated from rat brain, but CART is also synthesized and stored in the anterior pituitary. The localization of pituitary CART and factors regulating its synthesis are largely unknown. The regulation of pituitary CART synthesis and release in response to CRH and glucocorticoids was examined in vitro and in vivo. CART immunoreactivity (CART-IR) was released from anterior pituitary segments. This release was increased 15-fold in response to corticotropin-releasing hormone (CRH). Intraperitoneal administration of CRH to rats significantly increased plasma CART-IR. Furthermore, CART-IR content and plasma CART-IR were significantly increased in adrenalectomized rats, and anterior pituitary CART mRNA expression, CART-IR content, and plasma CART-IR were significantly decreased in corticosterone-treated rats. Plasma CART-IR showed a pattern of diurnal variation similar to that of ACTH and corticosterone, and plasma CART-IR was positively correlated with corticosterone. CART-IR was detectable in the medium of the corticotroph cell line AtT-20. Dual in situ hybridization for prepro-CART (ppCART) mRNA expression and immunocytochemistry for ACTH showed localization of ppCART mRNA to a subpopulation of ACTH-immunoreactive cells. These findings demonstrate that pituitary CART expression and release are regulated by CRH and the glucocorticoid environment and that pituitary CART is partly localized to corticotrophs.

corticotropin-releasing factor


Address for reprint requests and other correspondence: S. R. Bloom, Endocrine Unit, Faculty of Medicine, ICSTM, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK (E-mail: s.bloom{at}imperial.ac.uk).




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I. V. Ivanova, R. Schubert, D. B. Duridanova, T. B. Bolton, L. T. Lubomirov, and H. S. Gagov
Heart/Cardiac Muscle: Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frog
Exp Physiol, November 1, 2007; 92(6): 1037 - 1046.
[Abstract] [Full Text] [PDF]


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