Ontogeny and pathway of formation of 5α-androstane-3α,17β-diol in the testes of the immature brushtail possum Trichosurus vulpecula
Jean D. Wilson A B D , Geoffrey Shaw A , Marilyn B. Renfree A , Richard J. Auchus B , Michael W. Leihy A and Douglas C. Eckery CA Department of Zoology, University of Melbourne, Victoria 3010, Australia.
B Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8857, USA.
C AgResearch, Wallaceville Animal Research Centre, Ward Street, Upper Hutt, New Zealand.
D Corresponding author. Email: jwils1@mednet.swmed.edu
Reproduction, Fertility and Development 17(6) 603-609 https://doi.org/10.1071/RD05034
Submitted: 22 March 2005 Accepted: 8 May 2005 Published: 17 June 2005
Abstract
The testicular androgen 5α-androstane-3α,17β-diol (androstanediol) mediates virilisation in pouch young of a marsupial, the tammar wallaby, and is the principal androgen formed in immature rodent testes. To chart the pattern of androstanediol formation in another marsupial species, the testes or fragments of testes from brushtail possums (Trichosurus vulpecula) that spanned the age range from early pouch young to mature adults were incubated with 3H-progesterone and the products were identified by high-performance liquid chromatography. The only 19-carbon steroids identified in pouch young and adult testes were the Δ4-3-keto-steroids testosterone and androstenedione. However, androstanediol and another 5α-reduced androgen (androsterone) were synthesised by testes from Day 87–200 males and these appeared to be formed from the 5α-reduction and 3-keto reduction of testosterone and androstenedione. In the prostate and glans penis of the immature male, 3H-androstanediol was converted to dihydrotestosterone. We conclude that the timing of androstanediol formation in the possum testis resembles the process in rodents rather than in the tammar wallaby and that any androstanediol in the circulation probably acts in target tissues via conversion to dihydrotestosterone.
Extra keywords: dihydrotestosterone, epididymis, marsupial physiology, phallus, prostate, steroid 5α-reductase, virilisation.
Acknowledgments
This study was supported by grant 208911 from the National Health and Medical Research Council of Australia, by grant R21DK59942 from the National Institutes of Health and by grant C10X0218 from the Foundation for Research Science and Technology of New Zealand. The authors thank Evelyn Bauer, Brian Thomson and Michael Beaumont for technical assistance and for the care of the animals used in these experiments.
Attal, J. (1969). Levels of testosterone, androstenedione, estrone and estradiol-17β in the testes of fetal sheep. Endocrinology 85, 280–289.
| PubMed |
Bruchovsky, N. (1971). Comparison of the metabolites formed in rat prostate following the in vivo administration of seven natural androgens. Endocrinology 89, 1212–1222.
| PubMed |
Carmichael, R. , Belanger, A. , Cusan, L. , Seguin, C. , Caron, S. , and Labrie, F. (1980). Increased testicular 5α-androstane-3α,17β-diol formation induced by treatment with [D-Ser(TUB)6, des-Gly-NH210] LHRH ethylamide in the rat. Steroids 36, 383–391.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Chase, D. J. , and Payne, A. H. (1983). Changes in Leydig cell function during sexual maturation in the mouse. Biol. Reprod. 29, 1194–1200.
| PubMed |
Cook, B. , McDonald, I. R. , and Gibson, W. R. (1978). Prostatic function in the brush-tailed possum, Tricosurus vulpecula. J. Reprod. Fertil. 53, 369–375.
| PubMed |
Curlewis, J. D. , and Stone, G. M. (1985). Some effects of breeding season and castration on the prostate and epididymis of the brushtail possum, Trichosurus vulpecula. Aust. J. Biol. Sci. 38, 313–326.
| PubMed |
Eisler, J. A. , Tannenbaum, P. L. , Mann, D. R. , and Wallen, K. (1993). Neonatal testicular suppression with a GnRH agonist in rhesus monkeys: effects on adult endocrine function and behavior. Horm. Behav. 27, 551–567.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Frungieri, M. B. , Gonzalez-Calvar, S. I. , Bartke, A. , and Calandra, R. S. (1999). Influence of age and photoperiod on steroidogenic function of the testis of the golden hamster. Int. J. Androl. 22, 243–255.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Frye, C. A. , van Keuren, K. R. , and Erskine, M. S. (1996). Behavioral effects of 3α-androstanediol. I. Modulation of sexual receptivity and promotion of GABA-stimulated chloride flux. Behav. Brain Res. 79, 109–118.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Frye, C. A. , Rhodes, M. E. , Walf, A. , and Harney, J. P. (2002). Testosterone enhances aggression of wild-type mice but not those deficient in type I 5α-reductase. Brain Res. 948, 165–170.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ge, R.-S. , and Hardy, M. P. (1998). Variation in the end products of androgen biosynthesis and metabolism during postnatal differentiation of rat Leydig cells. Endocrinology 139, 3787–3795.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ge, R.-S. , Hardy, D. O. , Catterall, J. F. , and Hardy, M. P. (1999). Opposing changes in 3α-hydroxysteroid dehydrogenase oxidative and reductive activities in rat Leydig cells during pubertal development. Biol. Reprod. 60, 855–860.
| PubMed |
Gloyna, R. E. , and Wilson, J. D. (1969). A comparative study of the conversion of testosterone to 17β-hydroxy-5α-androstane-3-one (dihydrotestosterone) by prostate and epididymis. J. Clin. Endocrinol. Metab. 29, 970–977.
| PubMed |
Killian, J. , Pratis, K. , Clifton, R. J. , Stanton, P. G. , Robertson, D. M. , and O’Donnell, L. (2002). 5α-Reductase isoenzymes 1 and 2 in the rat testis during postnatal development. Biol. Reprod. 68, 1711–1718.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Leihy, M. W. , Shaw, G. , Wilson, J. D. , and Renfree, M. B. (2001). Virilization of the urogenital sinus of the tammar wallaby is not unique to 5α-androstane-3α,17β-diol. Mol. Cell. Endocrinol. 181, 111–115.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Leihy, M. W. , Shaw, G. , Wilson, J. D. , and Renfree, M. B. (2004). Penile development is initiated in the tammar wallaby pouch young during the period when 5α-androstane-3α,17β-diol is secreted by the testes. Endocrinology 145, 3346–3352.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lyne, A. G. , and Verhagen, A. M. W. (1957). Growth in the marsupial Trichosurus vulpecula and a comparison with some higher mammals. Growth 21, 167–195.
| PubMed |
Mahendroo, M. , Wilson, J. D. , Richardson, J. A. , and Auchus, R. J. (2004). Steroid 5α-reductase 1 promotes 5α-androstane-3α,17β-diol synthesis in immature mouse testes by two pathways. Mol. Cell. Endocrinol. 222, 113–120.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Mann, D. R. , Gould, K. G. , Collins, D. C. , and Wallen, K. (1989). Blockade of neonatal activation of the pituitary–testicular axis: effect on peripubertal luteinizing hormone and testosterone secretion and on testicular development in male monkeys. J. Clin. Endocrinol. Metab. 68, 600–607.
| PubMed |
Mann, D. R. , Akinbami, M. A. , Gould, K. G. , Paul, K. , and Wallen, K. (1998). Sexual maturation in male rhesus monkeys: importance of neonatal testosterone exposure and social rank. J. Endocrinol. 156, 493–501.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Moger, W. H. (1977). Serum 5α-androstane-3α,17β-diol, androsterone, and testosterone concentrations in the male rat. Influence of age and gonadotropin stimulation. Endocrinology 100, 1027–1032.
| PubMed |
Nakhla, A. M. , Ding, V. D. , Khan, M. S. , Romas, N. A. , Rhodes, L. , Smith, R. G. , and Rosner, W. (1995). 5α-Androstan-3α,17β-diol is a hormone: stimulation of cAMP accumulation in human and dog prostate. J. Clin. Endocrinol. Metab. 80, 2259–2262.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Nunlist, E. H. , Dozmorov, I. , Tang, Y. , Cowan, R. , Centola, M. , and Lin, H.-K. (2004). Partitioning of 5α-dihydrotestosterone and 5α-androstane-3α,17β-diol activated pathways for stimulating human prostate cancer LNCaP cell proliferation. J. Steroid Biochem. Mol. Biol. 91, 157–170.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Risbridger, G. P. , and Davies, A. (1994). Isolation of rat Leydig cells and precursor forms after administration of ethane dimethane sulfonate. Am. J. Physiol. 266, E975–E979.
| PubMed |
Shaw, G. , Renfree, M. B. , Leihy, M. W. , Shackleton, C. H. L. , Roitman, E. , and Wilson, J. D. (2000). Prostate formation in a marsupial is mediated by the testicular androgen 5α-androstane-3α,17β-diol. Proc. Natl Acad. Sci. USA 97, 12 256–12 259.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Sheffield, J. W. , and O’Shaughnessy, P. J. (1988). Testicular steroid metabolism during development in the normal and hypogonadal mouse. J. Endocrinol. 119, 257–264.
| PubMed |
Siiteri, P. K. , and Wilson, J. D. (1974). Testosterone formation and metabolism during male sexual differentiation in the human embryo. J. Clin. Endocrinol. Metab. 38, 113–125.
| PubMed |
Viger, R. S. , and Robaire, B. (1995). Steady state steroid 5α-reductase messenger ribonucleic acidlevels and immunocytochemical localization of the type 1 protein in the rat testis during postnatal development. Endocrinology 136, 5409–5415.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Weiss, M. (1986). Differences in steroid metabolism by tesits, prostate, and epididymis in the immature and adult possum (Trichosurus vulpepcula). Comp. Biochem. Physiol. 84B, 571–574.
Weiss, M. (1988). Factors influencing prostatic 5α-reductase activity in possum (Trichosurus vulpepcula). Comp. Biochem. Physiol. 89B, 21–26.
Wilson, J. D. (2001). The role of 5α-reduction in steroid hormone physiology. Reprod. Fertil. Dev. 13, 673–678.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wilson, J. D. , and Gloyna, R. E. (1970). The intranuclear metabolism of testosterone in the accessory organs of reproduction. Recent Prog. Horm. Res. 26, 309–336.
| PubMed |
Wilson, J. D. , and Siiteri, P. K. (1973). Developmental pattern of testosterone synthesis in the fetal gonad of the rabbit. Endocrinology 92, 1182–1191.
| PubMed |
Wilson, J. D. , Auchus, R. J. , Leihy, M. W. , Guryev, O. L. , Estabrook, R. W. , Osborn, S. M. , Shaw, G. , and Renfree, M. B. (2003). 5α-Androstane-3α,17β-diol is formed in tammar wallaby pouch young by a pathway involving 5α-pregnane-3α,17α-diol-20-one as a key intermediate. Endocrinology 144, 575–580.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
