| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Regular Article |
Impairs Androgen and Enhances Progesterone Biosynthesis in Primary Cultures of Porcine Theca Cells1
a Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Medical School, Charlottesville, Virginia 22908
Ovarian theca cells are the predominant source of gonadotropin-stimulated androgen biosynthesis in vivo. Troglitazone (TG), a synthetic agonist of the peroxisome proliferator-activated receptor 
(PPAR) and a thiazolidinedione used to treat insulin resistance, decreases serum androgen concentrations in women with hyperthecosis and/or polycystic ovary syndrome. Using reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated the presence of PPAR mRNA in the porcine ovary. Since activation of ovarian PPAR may alter hormone-stimulated steroidogenesis in vitro, we cultured porcine theca cells for 48 h in the presence of two different PPAR ligands, TG and 15-deoxy-
12,14-prostaglandin J2 (15d-PGJ2). Putative TG-mediated activation of PPAR resulted in a 53%–69% decrease in LH- and/or insulin-stimulated androstenedione and testosterone accumulation. Although TG reduced 3-isobutylmethylxanthine-enhanced LH-stimulated cAMP accumulation by 74%–78%, it did not alter basal cAMP concentrations. Exposure to 8Br-cAMP did not overcome the TG-induced inhibition of androgen accumulation. In contrast, TG administration amplified basal and hormone-stimulated progesterone accumulation, particularly in the presence of insulin, without altering levels of 17
-hydroxyprogesterone. The putative natural PPAR ligand, 15d-PGJ2, inhibited androgen biosynthesis and stimulated progesterone production. RT-PCR-based amplification of cytochrome P450 cholesterol side-chain cleavage (CYP11A) and cytochrome P450 17-hydroxylase/C-17,20-lyase (CYP17) transcripts indicated that TG moderately enhanced expression of these genes. However, TG did not affect CYP17 protein expression. We conclude that putative ligand-mediated activation of PPAR decreases LH- and/or insulin-driven theca cell androgen production by impairing the ability of CYP17 to synthesize androstenedione from available progestins. The corresponding augmentation of progesterone production could suggest that PPAR activation induces theca cell differentiation toward a progestin-synthesizing phenotype.
1 This research was supported in part by an NIH Training Grant 5T32 DK0764609 in Reproductive Neuroendocrinology (to P.D.S.), by NIH grants 16393 and HD 16806 (to J.D.V.), and by NICHD/NIH through cooperative agreement (U54 HD28934) as part of the Specialized Cooperative Centers Program in Reproduction Research.
2 Correspondence: Johannes D. Veldhuis, Endocrine Division, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908. FAX: 434 982 1911; jdv{at}virginia.edu
This article has been cited by other articles:
|
|
 |
|
  N. Tinfo and C. Komar Potential role for peroxisome proliferator-activated receptor {gamma} in regulating luteal lifespan in the rat Reproduction, January 1, 2007; 133(1): 187 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pasquali and A. Gambineri Insulin-sensitizing agents in polycystic ovary syndrome. Eur. J. Endocrinol., June 1, 2006; 154(6): 763 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Froment, F Gizard, D Defever, B Staels, J Dupont, and P Monget Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition. J. Endocrinol., May 1, 2006; 189(2): 199 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Banerjee and C. M Komar Effects of luteinizing hormone on peroxisome proliferator-activated receptor {gamma} in the rat ovary before and after the gonadotropin surge Reproduction, January 1, 2006; 131(1): 93 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E Minge, N. K. Ryan, K. H. V. D. Hoek, R. L. Robker, and R. J. Norman Troglitazone Regulates Peroxisome Proliferator-Activated Receptors and Inducible Nitric Oxide Synthase in Murine Ovarian Macrophages Biol Reprod, January 1, 2006; 74(1): 153 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jo, S. R. King, S. A. Khan, and D. M. Stocco Involvement of Protein Kinase C and Cyclic Adenosine 3',5'-Monophosphate-Dependent Kinase in Steroidogenic Acute Regulatory Protein Expression and Steroid Biosynthesis in Leydig Cells Biol Reprod, August 1, 2005; 73(2): 244 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ortega-Gonzalez, S. Luna, L. Hernandez, G. Crespo, P. Aguayo, G. Arteaga-Troncoso, and A. Parra Responses of Serum Androgen and Insulin Resistance to Metformin and Pioglitazone in Obese, Insulin-Resistant Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1360 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Froment, S. Fabre, J. Dupont, C. Pisselet, D. Chesneau, B. Staels, and P. Monget Expression and Functional Role of Peroxisome Proliferator-Activated Receptor-{gamma} in Ovarian Folliculogenesis in the Sheep Biol Reprod, November 1, 2003; 69(5): 1665 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. De Leo, A. la Marca, and F. Petraglia Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome Endocr. Rev., October 1, 2003; 24(5): 633 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Komar and T. E. Curry Jr Inverse Relationship Between the Expression of Messenger Ribonucleic Acid for Peroxisome Proliferator-Activated Receptor {gamma} and P450 Side Chain Cleavage in the Rat Ovary Biol Reprod, August 1, 2003; 69(2): 549 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Veldhuis, G. Zhang, and J. C. Garmey Troglitazone, an Insulin-Sensitizing Thiazolidinedione, Represses Combined Stimulation by LH and Insulin of de Novo Androgen Biosynthesis by Thecal Cells in Vitro J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1129 - 1133. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
