Testosterone is metabolised to the more potent androgen, dihydrotestosterone, by the 5alpha-reductase (5alphaR) enzyme. We previously showed that 5alpha-reduced androgens are important for maintaining androgen action on rat spermatogenesis when testicular testosterone concentrations are reduced. This study investigated expression and activity of the 5alphaR isoforms, type 1 (5alphaR-1) and type 2 (5alphaR-2), in the rat during hormone manipulation in order to understand the factors that regulate the testicular concentration of 5alphaR and testicular 5alpha-reduced androgen biosynthesis. Testicular 5alphaR-1 and 5alphaR-2 mRNA and enzyme activity were measured by real-time PCR and specific enzyme assays respectively. Hormone levels were first suppressed using two models of gonadotrophin suppression: testosterone and oestradiol treatment (LH/testosterone deficiency) or GnRH immunisation (LH/testosterone and FSH deficiency). Hormones were then either restored or suppressed for 6 days by a variety of hormonal treatments. 5alphaR-1 mRNA and enzyme activity increased when testosterone was suppressed, yet restoration of testosterone decreased 5alphaR-1 mRNA and enzyme activity, suggesting that testosterone negatively regulates 5alphaR-1. suppression of FSH decreased 5alphaR-1 mRNA yet FSH administration increased 5alphaR-1 mRNA, but no changes in 5alphaR-1 activity were observed within the 6 day period. In contrast to 5alphaR-1, testosterone did not affect the testicular concentration of 5alphaR-2 mRNA or activity, but there was evidence for modulation of 5alphaR-2 activity by FSH. Measurement of testicular androgens revealed that 5alphaR-1 was primarily responsible for the production of 5alpha-reduced metabolites. It is concluded that the 5alphaR isoforms in rat testis are differentially regulated by testosterone and FSH: testosterone negatively regulated 5alphaR-1 mRNA and enzyme activity but had no affect on 5alphaR-2, whereas FSH positively regulated 5alphaR-1 mRNA and appeared to regulate 5alphaR-2.

This article has been cited by other articles:

				S. M. Ruwanpura, R. I. McLachlan, P. G. Stanton, and S. J. Meachem Follicle-Stimulating Hormone Affects Spermatogonial Survival by Regulating the Intrinsic Apoptotic Pathway in Adult Rats Biol Reprod, April 1, 2008; 78(4): 705 - 713. [Abstract] [Full Text] [PDF]

				J. K. Amory, C. Wang, R. S. Swerdloff, B. D. Anawalt, A. M. Matsumoto, W. J. Bremner, S. E. Walker, L. J. Haberer, and R. V. Clark The Effect of 5{alpha}-Reductase Inhibition with Dutasteride and Finasteride on Semen Parameters and Serum Hormones in Healthy Men J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1659 - 1665. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson, R. I. McLachlan, L. O'Donnell, M. Frydenberg, D. M. Robertson, P. G. Stanton, and S. J. Meachem The Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in Maintaining Spermatogonial Maturation and Spermiation in Normal Men J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3962 - 3969. [Abstract] [Full Text] [PDF]

				M. J. Walton, R. A. L. Bayne, I. Wallace, D. T. Baird, and R. A. Anderson Direct Effect of Progestogen on Gene Expression in the Testis during Gonadotropin Withdrawal and Early Suppression of Spermatogenesis J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2526 - 2533. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson and R. I. McLachlan Male hormonal contraception: concept proven, product in sight? Hum. Reprod. Update, July 1, 2006; 12(4): 463 - 482. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson, P. G. Stanton, L. O'Donnell, S. J. Meachem, J. K. Amory, R. Berger, W. J. Bremner, and R. I. McLachlan Effects of Testosterone and Levonorgestrel Combined with a 5{alpha}-Reductase Inhibitor or Gonadotropin-Releasing Hormone Antagonist on Spermatogenesis and Intratesticular Steroid Levels in Normal Men J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5647 - 5655. [Abstract] [Full Text] [PDF]

				M. B. Frungieri, A. Mayerhofer, K. Zitta, O. P. Pignataro, R. S. Calandra, and S. I. Gonzalez-Calvar Direct Effect of Melatonin on Syrian Hamster Testes: Melatonin Subtype 1a Receptors, Inhibition of Androgen Production, and Interaction with the Local Corticotropin-Releasing Hormone System Endocrinology, March 1, 2005; 146(3): 1541 - 1552. [Abstract] [Full Text] [PDF]

				R. I. McLachlan, D. M. Robertson, E. Pruysers, A. Ugoni, A. M. Matsumoto, B. D. Anawalt, W. J. Bremner, and C. Meriggiola Relationship between Serum Gonadotropins and Spermatogenic Suppression in Men Undergoing Steroidal Contraceptive Treatment J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 142 - 149. [Abstract] [Full Text] [PDF]