This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, X. Articles by Menon, K. M. J. Search for Related Content PubMed PubMed Citation Articles by Li, X. Articles by Menon, K. M. J.

Regulation of High Density Lipoprotein Receptor Messenger Ribonucleic Acid Expression and Cholesterol Transport in Theca-Interstitial Cells by Insulin and Human Chorionic Gonadotropin¹

Departments of Obstetrics and Gynecology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Dr. K. M. J. Menon, 6428 Med Sci I, 1300 Catherine Street, University of Michigan, Ann Arbor, Michigan 48109. E-mail: kmjmenon{at}umich.edu

The synthesis of androgens by theca-interstitial cells is stimulated by LH and the insulin/insulin-like growth factor I (IGF-I) system. An essential element of the steroidogenesis is the uptake of plasma cholesterol and transformation to steroid hormones. In the rat, the uptake of cholesterol by the theca-interstitial cells is mediated by the high density lipoprotein receptor. The goal of the present study was to examine whether insulin has any effect on cholesterol delivery into theca-interstitial cells. The effects of insulin and hCG on the expression of the high density lipoprotein receptor (SR-BI) messenger RNA (mRNA) and intracellular cholesterol levels were examined in rat theca-interstitial cells under in vivo and in vitro conditions. Twenty-five-day-old rats were treated with insulin, hCG, or insulin followed by hCG. The expression of SR-BI mRNA was then examined in ovaries enriched in theca-interstitial cell population by Northern blot analysis. Treatment with insulin increased the expression of SR-BI mRNA over that in controls treated with saline. hCG administration also increased the expression of SR-BI mRNA. A combination of insulin followed by hCG produced an even greater increase in SR-BI mRNA expression. Measurements of cellular cholesterol in the ovarian tissue showed an increase in total and free cholesterol levels in response to insulin treatment. As expected, administration of hCG produced a depletion of cellular cholesterol, and the depletion was even more pronounced in response to treatment with insulin and hCG. The effect of insulin and hCG on SR-SBI mRNA expression was then examined under in vitro conditions using primary cultures of theca-interstitial cells. Treatment with insulin produced an increase in SR-BI mRNA expression. As the cultured theca-interstitial cells were not able to maintain hCG receptors, hCG addition produced no increase in SR-BI mRNA expression. However, in the presence of insulin, these cells were able to maintain hCG receptors and readily responded to hCG to increase SR-BI mRNA expression. Although insulin alone produced a modest increase in total and free cholesterol levels, in the presence of insulin, hCG produced the expected depletion of cellular cholesterol content. The present study shows that insulin has a stimulatory effect on the expression of high density lipoprotein receptors in theca-interstitial cells, suggesting that one of the actions of insulin is to increase intracellular cholesterol, which is subsequently mobilized for androgen biosynthesis in theca-interstitial cells.

This article has been cited by other articles:

				R.W. Browne, W.B. Shelly, M.S. Bloom, A.J. Ocque, J.R. Sandler, H.G. Huddleston, and V.Y. Fujimoto Distributions of high-density lipoprotein particle components in human follicular fluid and sera and their associations with embryo morphology parameters during IVF Hum. Reprod., August 1, 2008; 23(8): 1884 - 1894. [Abstract] [Full Text] [PDF]

				L. Miranda-Jimenez and B. D. Murphy Lipoprotein receptor expression during luteinization of the ovarian follicle Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1053 - E1061. [Abstract] [Full Text] [PDF]

				L. Wang and K. M. J. Menon Regulation of Luteinizing Hormone/Chorionic Gonadotropin Receptor Messenger Ribonucleic Acid Expression in the Rat Ovary: Relationship to Cholesterol Metabolism Endocrinology, January 1, 2005; 146(1): 423 - 431. [Abstract] [Full Text] [PDF]

				L. P. Mayer, P. J. Devine, C. A. Dyer, and P. B. Hoyer The Follicle-Deplete Mouse Ovary Produces Androgen Biol Reprod, July 1, 2004; 71(1): 130 - 138. [Abstract] [Full Text] [PDF]

				Q. Wu, S. Sucheta, S. Azhar, and K. M. J. Menon Lipoprotein Enhancement of Ovarian Theca-Interstitial Cell Steroidogenesis: Relative Contribution of Scavenger Receptor Class B (Type I) and Adenosine 5'-Triphosphate- Binding Cassette (Type A1) Transporter in High-Density Lipoprotein-Cholesterol Transport and Androgen Synthesis Endocrinology, June 1, 2003; 144(6): 2437 - 2445. [Abstract] [Full Text] [PDF]

				C. R. O. Carvalho, J. B. C. Carvalheira, M. H. M. Lima, S. F. Zimmerman, L. C. Caperuto, A. Amanso, A. L. Gasparetti, V. Meneghetti, L. F. Zimmerman, L. A. Velloso, et al. Novel Signal Transduction Pathway for Luteinizing Hormone and Its Interaction with Insulin: Activation of Janus Kinase/Signal Transducer and Activator of Transcription and Phosphoinositol 3-Kinase/Akt Pathways Endocrinology, February 1, 2003; 144(2): 638 - 647. [Abstract] [Full Text] [PDF]

				S. L. Lay, I. Lefrere, C. Trautwein, I. Dugail, and S. Krief Insulin and Sterol-regulatory Element-binding Protein-1c (SREBP-1C) Regulation of Gene Expression in 3T3-L1 Adipocytes. IDENTIFICATION OF CCAAT/ENHANCER-BINDING PROTEIN beta AS AN SREBP-1C TARGET J. Biol. Chem., September 13, 2002; 277(38): 35625 - 35634. [Abstract] [Full Text] [PDF]