Endocrinology, Vol 135, 1372-1377, Copyright © 1994 by Endocrine Society

ARTICLES

Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse

L Murphy, IA Jeffcoate and PJ O'Shaughnessy
Department of Veterinary Physiology, University of Glasgow Veterinary School, Scotland.

Leydig cells are the major source of androgens in the male, and it is likely that these cells are also targets for androgen action. The role of androgen action in regulating the development of Leydig cell function has been determined using the testicular feminized (Tfm/Y) mouse, which lacks androgen receptors. In Tfm mice, the testes fail to descend at the normal time (25 days), and testicular descent was, therefore, surgically prevented in control (+/Y) animals. The activity of 3 beta-hydroxysteroid dehydrogenase increased during development from 5-40 days in control and Tfm mice, with no significant difference between the groups. In control animals, 17 alpha-hydroxylase activity was low from 5-25 days, at which time there was a 26-fold increase up to 40 days. In the Tfm group, 17 alpha-hydroxylase activity was 4-fold higher than that in controls on day 5, but showed no change in activity after 25 days and remained at neonatal levels up to 40 days. The activity of 17-ketosteroid reductase in the control animals showed a developmental pattern similar to that of 17 alpha-hydroxylase, with a marked increase in activity after 25 days. In the Tfm group, 17- ketosteroid reductase was normal on day 5, but failed to show any significant change thereafter and remained at neonatal levels on day 40. Serum LH levels in control animals increased from 5 days to a peak at 30 days. In Tfm mice, LH levels were significantly increased on days 20 and 40, but did not differ from controls on days 5, 25, and 30. In control +/Y animals, in which normal testicular descent was allowed to proceed at 25 days, the pattern of development was similar to that in the cryptorchid +/Y animals, although the increase in 17 alpha- hydroxylase activity at 30 and 40 days was significantly greater. The results show 1) that fetal Leydig cell steroidogenesis is enhanced in the absence of androgen receptors, but 2) that adult Leydig cells require receptor-mediated androgen activity around day 25 for normal functional development. In addition, 3) the lack of testicular descent at 25 days reduces the pubertal rise in 17 alpha-hydroxylase activity.

This article has been cited by other articles:

				S. M. Eacker, N. Agrawal, K. Qian, H. L. Dichek, E.-Y. Gong, K. Lee, and R. E. Braun Hormonal Regulation of Testicular Steroid and Cholesterol Homeostasis Mol. Endocrinol., March 1, 2008; 22(3): 623 - 635. [Abstract] [Full Text] [PDF]

				S. M. Eacker, J. E. Shima, C. M. Connolly, M. Sharma, R. W. Holdcraft, M. D. Griswold, and R. E. Braun Transcriptional Profiling of Androgen Receptor (AR) Mutants Suggests Instructive and Permissive Roles of AR Signaling in Germ Cell Development Mol. Endocrinol., April 1, 2007; 21(4): 895 - 907. [Abstract] [Full Text] [PDF]

				D. H. Volle, R. Duggavathi, B. C. Magnier, S. M. Houten, C. L. Cummins, J.-M. A. Lobaccaro, G. Verhoeven, K. Schoonjans, and J. Auwerx The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice Genes & Dev., February 1, 2007; 21(3): 303 - 315. [Abstract] [Full Text] [PDF]

				P. J. O'Shaughnessy, H. Johnston, L. Willerton, and P. J. Baker Failure of normal adult Leydig cell development in androgen-receptor-deficient mice J. Cell Sci., January 9, 2002; 115(17): 3491 - 3496. [Abstract] [Full Text] [PDF]

				S.M.L. Chamindrani Mendis-Handagama and H.B. Siril Ariyaratne Differentiation of the Adult Leydig Cell Population in the Postnatal Testis Biol Reprod, September 1, 2001; 65(3): 660 - 671. [Abstract] [Full Text] [PDF]

				L. Gnessi, S. Basciani, S. Mariani, M. Arizzi, G. Spera, C. Wang, C. Bondjers, L. Karlsson, and C. Betsholtz Leydig Cell Loss and Spermatogenic Arrest in Platelet-derived Growth Factor (PDGF)-A-deficient Mice J. Cell Biol., May 29, 2000; 149(5): 1019 - 1026. [Abstract] [Full Text] [PDF]

				Y.-m. Qian and W.-C. Song Regulation of Estrogen Sulfotransferase Expression in Leydig Cells by Cyclic Adenosine 3',5'-Monophosphate and Androgen Endocrinology, March 1, 1999; 140(3): 1048 - 1053. [Abstract] [Full Text]

				K. Takamiya, A. Yamamoto, K. Furukawa, J. Zhao, S. Fukumoto, S. Yamashiro, M. Okada, M. Haraguchi, M. Shin, M. Kishikawa, et al. Complex gangliosides are essential in spermatogenesis of mice: Possible roles in the transport of testosterone PNAS, October 13, 1998; 95(21): 12147 - 12152. [Abstract] [Full Text] [PDF]

				G. Smithson, J. F. Couse, D. B. Lubahn, K. S. Korach, and P. W. Kincade The Role of Estrogen Receptors and Androgen Receptors in Sex Steroid Regulation of B Lymphopoiesis J. Immunol., July 1, 1998; 161(1): 27 - 34. [Abstract] [Full Text] [PDF]