Endocrinology, Vol 133, 2277-2283, Copyright © 1993 by Endocrine Society

ARTICLES

Differential regulation of steroidogenic enzymes during differentiation optimizes testosterone production by adult rat Leydig cells

LX Shan, DM Phillips, CW Bardin and MP Hardy
Population Council, New York, New York 10021.

The postnatal differentiation of rat Leydig cells may be subdivided into three stages based on morphology and steroid production. The purpose of this study was to clarify the developmental mechanisms underlying increased testosterone production by measuring steady state levels of the mRNAs for three steroidogenic enzymes in isolated Leydig cells at each stage of differentiation. These include Leydig cell progenitors on day 21, immature Leydig cells on day 35, and adult Leydig cells on day 90. The steroidogenic enzymes were 1) cholesterol side-chain cleavage enzyme (CSCC), 2) 17 alpha-hydroxylase (P450-17 alpha), and 3) 3 alpha-hydroxysteroid dehydrogenase (3 alpha HSD). We report that levels of CSCC and P450-17 alpha mRNAs increase, whereas 3 alpha HSD mRNA levels decline during the course of Leydig cell differentiation. The levels of 3 alpha HSD mRNA were high in progenitor Leydig cells that appeared to contain little smooth endoplasmic reticulum and decreased in cells as smooth endoplasmic reticulum developed and other enzyme mRNAs increased. These observations suggest that the factors that regulate 3 alpha HSD mRNA levels are startlingly different from those that regulate the mRNA levels of CSCC and P450-17 alpha. We conclude that the progressive increase in the capacity of differentiating Leydig cells to produce testosterone can be explained in part by an increase in the activity of enzymes that synthesize testosterone (CSCC and P450-17 alpha) and a decrease in the activity of an enzyme that metabolizes testosterone and its precursors (3 alpha HSD).

This article has been cited by other articles:

				G.-R. Chen, R.-S. Ge, H. Lin, L. Dong, C. M. Sottas, and M. P. Hardy Development of a cryopreservation protocol for Leydig cells Hum. Reprod., August 1, 2007; 22(8): 2160 - 2168. [Abstract] [Full Text] [PDF]

				C. N Kahiri, M W. Khalil, F. Tekpetey, and G. M Kidder Leydig cell function in mice lacking connexin43. Reproduction, October 1, 2006; 132(4): 607 - 616. [Abstract] [Full Text] [PDF]

				R.-S. Ge, Q. Dong, C. M. Sottas, H. Chen, B. R. Zirkin, and M. P. Hardy Gene Expression in Rat Leydig Cells During Development from the Progenitor to Adult Stage: A Cluster Analysis Biol Reprod, June 1, 2005; 72(6): 1405 - 1415. [Abstract] [Full Text] [PDF]

				G.-M. Wang, P. J. O'Shaughnessy, C. Chubb, B. Robaire, and M. P. Hardy Effects of Insulin-Like Growth Factor I on Steroidogenic Enzyme Expression Levels in Mouse Leydig Cells Endocrinology, November 1, 2003; 144(11): 5058 - 5064. [Abstract] [Full Text] [PDF]

				Z. Zhang, A. Z. Wu, Z.-M. Feng, D. Mruk, C. Y. Cheng, and C.-L. C. Chen Gonadotropins, via cAMP, Negatively Regulate GATA-1 Gene Expression in Testicular Cells Endocrinology, March 1, 2002; 143(3): 829 - 836. [Abstract] [Full Text] [PDF]

				D. O. Hardy, R.-S. Ge, J. F. Catterall, Y.-t. Hou, T. M. Penning, and M. P. Hardy Identification of the Oxidative 3{alpha}-Hydroxysteroid Dehydrogenase Activity of Rat Leydig Cells as Type II Retinol Dehydrogenase Endocrinology, May 1, 2000; 141(5): 1608 - 1617. [Abstract] [Full Text] [PDF]

				M. Kanzaki and P. L. Morris Growth Hormone Regulates Steroidogenic Acute Regulatory Protein Expression and Steroidogenesis in Leydig Cell Progenitors Endocrinology, April 1, 1999; 140(4): 1681 - 1686. [Abstract] [Full Text]

				R.-S. Ge, D. O. Hardy, J. F. Catterall, and M. P. Hardy Opposing Changes in 3{alpha}-Hydroxysteroid Dehydrogenase Oxidative and Reductive Activities in Rat Leydig Cells during Pubertal Development Biol Reprod, April 1, 1999; 60(4): 855 - 860. [Abstract] [Full Text]

				R.-S. Ge and M. P. Hardy Variation in the End Products of Androgen Biosynthesis and Metabolism during Postnatal Differentiation of Rat Leydig Cells Endocrinology, September 1, 1998; 139(9): 3787 - 3795. [Abstract] [Full Text] [PDF]

				R.-S. Ge, D. O. Hardy, J. F. Catterall, and M. P. Hardy Developmental Changes in Glucocorticoid Receptor and 11{beta}-Hydroxysteroid Dehydrogenase Oxidative and Reductive Activities in Rat Leydig Cells Endocrinology, December 1, 1997; 138(12): 5089 - 5095. [Abstract] [Full Text] [PDF]

				R.-s. Ge and M. P. Hardy Decreased Cyclin A2 and Increased Cyclin G1 Levels Coincide with Loss of Proliferative Capacity in Rat Leydig Cells During Pubertal Development Endocrinology, September 1, 1997; 138(9): 3719 - 3726. [Abstract] [Full Text] [PDF]

				L.-X. Shan, C. W. Bardin, and M. P. Hardy Immunohistochemical Analysis of Androgen Effects on Androgen Receptor Expression in Developing Leydig and Sertoli Cells Endocrinology, March 1, 1997; 138(3): 1259 - 1266. [Abstract] [Full Text] [PDF]