This Article Full Text Full Text (PDF) 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 Shan, L.-X. Articles by Hardy, M. P. Search for Related Content PubMed PubMed Citation Articles by Shan, L.-X. Articles by Hardy, M. P.

Immunohistochemical Analysis of Androgen Effects on Androgen Receptor Expression in Developing Leydig and Sertoli Cells¹

Center for Biomedical Research, The Population Council, New York, New York 10021

Address all correspondence and requests for reprints to: Matthew P. Hardy, The Population Council, 1230 York Avenue, New York, New York 10021. E-mail: hardy{at}popcbr.rockefeller.edu

Leydig and Sertoli cells are both targets of androgen action in the testis. Androgen exerts contrasting effects on the two cell types: partially inhibiting steroidogenesis in adult Leydig cell and stimulating adult Sertoli cell functions required to support spermatogenesis. The developmental changes in the messenger RNA (mRNA) levels of androgen receptor (AR) also differ between Leydig and Sertoli cells, with Leydig cell AR mRNA being highest on day 35 postpartum, whereas Sertoli cell AR mRNA levels are highest on day 90. The purpose of the present study was to determine if the concentrations of AR in Leydig and Sertoli cells are differentially regulated during development using quantitative immunostaining. AR protein levels were measured in rat testes after hormonal treatments at three developmental stages: on days 21, 35, and 90 postpartum. At each age, five groups of animals were treated for 4 days with: 1) vehicle; 2) LHRH antagonist (NalGlu, 0.3 mg/kg BW·day) to suppress endogenous levels of androgen that accompany inhibition of LH and FSH secretion; 3) NalGlu + LH (0.2 mg/kg BW·day); 4) NalGlu + testosterone (T, at 7.5 mg/kg BW·day); and 5) NalGlu + MENT (a potent synthetic androgen, 7-methyl-19-nortestosterone, 0.7 mg/kg BW·day). AR protein was visualized by immunohistochemistry and measured by computer-assisted image analysis in Leydig and Sertoli cells using frozen sections of testes. After NalGlu treatment, AR levels in Leydig cells declined sharply to 42% and 31% of vehicle control (P < 0.01) in the 21 and 35 days postpartum age groups, respectively, but in 90-day-old rats there was no change. AR levels were partially maintained by exogenous LH, and completely maintained by exogenous androgen treatments in Leydig cells from 21- and 35-day-old rats, whereas in Leydig cells from 90-day-old rats, AR levels were unaffected in all treatment groups. In contrast, after NalGlu treatment, the AR concentration in Sertoli cells from 90-day-old rats were reduced to 32% of control (P < 0.01). Moreover, in Sertoli cells from 90-day-old rats, AR levels were partially maintained by LH and completely maintained by androgens. A similar trend was observed on day 35. On day 21, however, AR levels in immature Sertoli cells were unaffected in all treatment groups. These results indicate that androgen maximally stimulates AR levels in immature Leydig cells but is without significant effect in adult Leydig cells. In contrast, AR levels in Sertoli cells are more sensitive to androgen regulation in adult compared with immature animals. These findings indicate that there are distinct mechanisms controlling AR concentrations in Leydig and Sertoli cells during the development of the testis.

This article has been cited by other articles:

				W.-Y. Lui and W. M Lee Molecular mechanisms by which hormones and cytokines regulate cell junction dynamics in the testis J. Mol. Endocrinol., August 1, 2009; 43(2): 43 - 51. [Abstract] [Full Text] [PDF]

				H. H Ortega, N. R Salvetti, and V. Padmanabhan Developmental programming: prenatal androgen excess disrupts ovarian steroid receptor balance Reproduction, May 1, 2009; 137(5): 865 - 877. [Abstract] [Full Text] [PDF]

				H. H. N. Yan, D. D. Mruk, W. M. Lee, and C. Y. Cheng Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells FASEB J, June 1, 2008; 22(6): 1945 - 1959. [Abstract] [Full Text] [PDF]

				J. S. Rocha, M. S. Bonkowski, L. R. Franca, and A. Bartke Mild Calorie Restriction Does Not Affect Testosterone Levels and Testicular Gene Expression in Mutant Mice Experimental Biology and Medicine, September 1, 2007; 232(8): 1050 - 1063. [Abstract] [Full Text] [PDF]

				R.-S. Wang, S. Yeh, L.-M. Chen, H.-Y. Lin, C. Zhang, J. Ni, C.-C. Wu, P. A. di Sant'Agnese, K. L. deMesy-Bentley, C.-R. Tzeng, et al. Androgen Receptor in Sertoli Cell Is Essential for Germ Cell Nursery and Junctional Complex Formation in Mouse Testes Endocrinology, December 1, 2006; 147(12): 5624 - 5633. [Abstract] [Full Text] [PDF]

				T. F. M. Mikkila, J. Toppari, and J. Paranko Effects of Neonatal Exposure to 4-Tert-Octylphenol, Diethylstilbestrol, and Flutamide on Steroidogenesis in Infantile Rat Testis Toxicol. Sci., June 1, 2006; 91(2): 456 - 466. [Abstract] [Full Text] [PDF]

				Q. Zhou, J. E. Shima, R. Nie, P. J. Friel, and M. D. Griswold Androgen-Regulated Transcripts in the Neonatal Mouse Testis as Determined Through Microarray Analysis Biol Reprod, April 1, 2005; 72(4): 1010 - 1019. [Abstract] [Full Text] [PDF]

				C. Chang, Y.-T. Chen, S.-D. Yeh, Q. Xu, R.-S. Wang, F. Guillou, H. Lardy, and S. Yeh Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells PNAS, May 4, 2004; 101(18): 6876 - 6881. [Abstract] [Full Text] [PDF]

				J. Xu, A. R. Beyer, W. H. Walker, and E. A. McGee Developmental and Stage-Specific Expression of Smad2 and Smad3 in Rat Testis J Androl, March 1, 2003; 24(2): 192 - 200. [Abstract] [Full Text] [PDF]

				C.M. Luetjens, J. Gromoll, M. Engelhardt, S. von Eckardstein, M. Bergmann, E. Nieschlag, and M. Simoni Manifestation of Y-chromosomal deletions in the human testis: a morphometrical and immunohistochemical evaluation Hum. Reprod., September 1, 2002; 17(9): 2258 - 2266. [Abstract] [Full Text] [PDF]

				J. R. Latendresse, A. R. Warbrittion, H. Jonassen, and D. M. Creasy Fixation of Testes and Eyes Using a Modified Davidson's Fluid: Comparison with Bouin's Fluid and Conventional Davidson's Fluid Toxicol Pathol, June 1, 2002; 30(4): 524 - 533. [Abstract] [PDF]

				S. Maiti, M. L. Meistrich, G. Wilson, G. Shetty, M. Marcelli, M. J. McPhaul, P. L. Morris, and M. F. Wilkinson Irradiation Selectively Inhibits Expression from the Androgen-Dependent Pem Homeobox Gene Promoter in Sertoli Cells Endocrinology, April 1, 2001; 142(4): 1567 - 1577. [Abstract] [Full Text]

				L.-J. Zhu, M. P. Hardy, I. V. Inigo, I. Huhtaniemi, C. W. Bardin, and A. J. Moo-Young Effects of Androgen on Androgen Receptor Expression in Rat Testicular and Epididymal Cells: A Quantitative Immunohistochemical Study Biol Reprod, August 1, 2000; 63(2): 368 - 376. [Abstract] [Full Text]

				H. F. S. Huang, M.-T. Li, W. Giglio, R. Anesetti, J. E. Ottenweller, and L. M. Pogach The Detrimental Effects of Spinal Cord Injury on Spermatogenesis in the Rat Is Partially Reversed by Testosterone, but Enhanced by Follicle- Stimulating Hormone Endocrinology, March 1, 1999; 140(3): 1349 - 1355. [Abstract] [Full Text]