HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Shen, X. Articles by Friedman, T. C. Search for Related Content PubMed PubMed Citation Articles by Shen, X. Articles by Friedman, T. C.

Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter

¹Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine & Sciences, University of California Los Angeles School of Medicine; and ²Division of Endocrinology, Department of Medicine, West Los Angeles Veterans Affairs Medical Center, Los Angeles, California

Submitted 29 March 2004 ; accepted in final form 4 August 2004

The prohormone convertases (PCs) PC1 and PC2 are involved in the tissue-specific endoproteolytic processing of neuropeptide precursors within the secretory pathway. We previously showed that changes in thyroid status altered pituitary PC2 mRNA and that this regulation was due to triiodothyronine-dependent interaction of the thyroid hormone receptor (TR) with negative thyroid hormone response elements (nTREs) contained in a large proximal region of the human PC2 promoter. In the current study, we examined the in vivo regulation of brain PC2 mRNA by thyroid status and found that 6-n-propyl-2-thiouracil-induced hypothyroidism stimulated, whereas thyroxine-induced hyperthyroidism suppressed, PC2 mRNA levels in the rat hypothalamus and cerebral cortex. To address the mechanism of T₃ regulation of the PC2 gene, we used human PC2 (hPC2) promoter constructs transiently transfected into GH3 cells and found that triiodothyronine negatively and 9-cis-retinoic acid positively regulated hPC2 promoter activity. EMSAs, using purified TR1 and retinoid X receptor- (RXR) proteins demonstrated that TR bound the distal putative nTRE-containing oligonucleotide in the PC2 promoter, and RXR bound to both nTRE-containing oligonucleotides. EMSAs with oligonucleotides containing deletion mutations of the nTREs demonstrated that the binding to TR and RXR separately is reduced, but specific binding to TR and RXR together persists even with deletion of each putative nTRE. We conclude that there are two novel TRE-like sequences in the hPC2 promoter and that these regions act in concert in a unique manner to facilitate the effects of thyroid hormone and 9-cis-retinoic acid on PC2.

posttranslational processing; hypothyroidism; prohormone convertase; pituitary; regulation

This article has been cited by other articles:

				V. P. Espinosa, M. Ferrini, X. Shen, K. Lutfy, E. A. Nillni, and T. C. Friedman Cellular colocalization and coregulation between hypothalamic pro-TRH and prohormone convertases in hypothyroidism Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E175 - E186. [Abstract] [Full Text] [PDF]

				M. Nygard, N. Becker, B. Demeneix, K. Pettersson, and M. Bondesson Thyroid hormone-mediated negative transcriptional regulation of Necdin expression. J. Mol. Endocrinol., June 1, 2006; 36(3): 517 - 530. [Abstract] [Full Text] [PDF]