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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/E175    most recent 00288.2006v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Espinosa, V. P. Articles by Friedman, T. C. Search for Related Content PubMed PubMed Citation Articles by Espinosa, V. P. Articles by Friedman, T. C.

Cellular colocalization and coregulation between hypothalamic pro-TRH and prohormone convertases in hypothyroidism

¹Division of Endocrinology, Department of Medicine, Charles R. Drew University of Medicine and Sciences, University of California Los Angeles School of Medicine, Los Angeles; ²Division of Urology, Research and Education Institute, Harbor-University of California Los Angeles Medical Center, Torrance; ³College of Pharmacy, Western University of Health Sciences, Pomona, California; and ⁴Division of Endocrinology, Department of Medicine, Brown Medical School, Rhode Island Hospital, Providence, Rhode Island

Submitted 16 June 2006 ; accepted in final form 21 August 2006

The prohormone convertases (PCs), PC1/3 and PC2, are involved in the tissue-specific endoproteolytic posttranslational processing of many hormonal precursors within the secretory pathway. One important prohormone, pro-thyrotropin-releasing hormone (TRH), is expressed in both hypophysiotropic (where it regulates the secretion of thyroid-stimulating hormone) and nonhypophysiotropic regions of the brain. Pro-TRH is processed at specific sites in the secretory pathway, primarily by PC1/3 followed by PC2. We hypothesized that thyroid hormone status in specific nuclei of the brain would alter pro-TRH processing by inducing changes in PC1/3 and PC2 expression. Therefore, we examined pro-TRH, PC1/3, and PC2 coexpression and coregulation in the paraventricular nucleus (PVN), lateral hypothalamus (LH), and ventromedial nucleus (VMN) of hypothyroid and euthyroid rats. Our results show that 6-n-propyl-2-thiouracil (PTU) treatment producing hypothyroidism induced a significant increase in the expression of PC1/3, PC2, and pro-TRH in the PVN and LH, but not VMN. When confocal studies were performed, an increase in colocalization of PC1/3 or PC2 in pro-TRH was observed only in PVN, a response that was especially prominent in the ventral and medial areas of the PVN. PTU did not regulate colocalization in the VMH or LH. Regulation of colocalization of processing enzyme and prohormone expression is a novel mechanism to alter hormonal biosynthesis.

posttranslational processing; hyperthyroidism; hypothyroidism; prohormone convertase; hypothalamus; pro-thyrotropin-releasing hormone; peptide