5α-androstane-3α, 17β-diol is formed in tammar wallaby pouch young testes by a pathway involving 5α-pregnane-3α, 17α-diol-20-one as a key intermediate

The synthetic pathway by which 5α-androstane-3α,17β-diol (5α-adiol) is formed in the testes of tammar wallaby pouch young was investigated by incubating testes from d 20–40 males with various radioactive precursors and analyzing the metabolites by thin-layer chromatography and HPLC. [3H]Progesterone was converted to 17-hydroxyprogesterone, which was converted to 5α-adiol by two pathways: One involves the formation of testosterone and dihydrotestosterone as intermediates, and the other involves formation of 5α-pregnane-3α,17α-diol-20-one (5α-pdiol) and androsterone as intermediates. Formation of 5α-adiol from both [3H]testosterone and [3H]progesterone was blocked by the 5α-reductase inhibitor 4MA. The addition of nonradioactive 5α-pdiol blocked the conversion of [3H]progesterone to 5α-adiol, and [3H]5α-pdiol was efficiently converted to androsterone and 5α-adiol. We conclude that expression of steroid 5α-reductase in the developing wallaby testes allows formation of 5α-reduced androgens by a pathway that d...

[1]  G. Shaw,et al.  Administration of 5α-Androstane-3α,17β-Diol to Female Tammar Wallaby Pouch Young Causes Development of a Mature Prostate and Male Urethra. , 2002, Endocrinology.

[2]  G. Shaw,et al.  Virilization of the urogenital sinus of the tammar wallaby is not unique to 5α-androstane-3α,17β-diol , 2001, Molecular and Cellular Endocrinology.

[3]  J. Schramm,et al.  Characterization of the 5α-Reductase-3α-Hydroxysteroid Dehydrogenase Complex in the Human Brain1 , 2001 .

[4]  G. Ooi,et al.  Enzyme assay for 5α-reductase Type 2 activity in the presence of 5α-reductase Type 1 activity in rat testis , 2000, The Journal of Steroid Biochemistry and Molecular Biology.

[5]  G. Shaw,et al.  Prostate formation in a marsupial is mediated by the testicular androgen 5α-androstane-3α,17β-diol , 2000 .

[6]  R. Calandra,et al.  Influence of age and photoperiod on steroidogenic function of the testis in the golden hamster. , 1999, International journal of andrology.

[7]  J. Wilson,et al.  Virilization of the male pouch young of the tammar wallaby does not appear to be mediated by plasma testosterone or dihydrotestosterone. , 1999, Biology of reproduction.

[8]  D. Hardy,et al.  Opposing changes in 3alpha-hydroxysteroid dehydrogenase oxidative and reductive activities in rat leydig cells during pubertal development. , 1999, Biology of reproduction.

[9]  M. Hardy,et al.  Variation in the End Products of Androgen Biosynthesis and Metabolism during Postnatal Differentiation of Rat Leydig Cells * , 1998 .

[10]  W. Miller,et al.  Cytochrome b 5 Augments the 17,20-Lyase Activity of Human P450c17 without Direct Electron Transfer* , 1998, The Journal of Biological Chemistry.

[11]  D. Moller,et al.  Sex hormone-binding globulin mediates prostate androgen receptor action via a novel signaling pathway. , 1998, Endocrinology.

[12]  C. Frye,et al.  Behavioral effects of 3α-androstanediol I: modulation of sexual receptivity and promotion of GABA-stimulated chloride flux , 1996, Behavioural Brain Research.

[13]  B. Robaire,et al.  Steady state steroid 5 alpha-reductase messenger ribonucleic acid levels and immunocytochemical localization of the type 1 protein in the rat testis during postnatal development. , 1995, Endocrinology.

[14]  M. S. Khan,et al.  5 alpha-Androstan-3 alpha,17 beta-diol is a hormone: stimulation of cAMP accumulation in human and dog prostate. , 1995, The Journal of clinical endocrinology and metabolism.

[15]  G. Risbridger,et al.  Isolation of rat Leydig cells and precursor forms after administration of ethane dimethane sulfonate. , 1994, The American journal of physiology.

[16]  P. O’Shaughnessy,et al.  Testicular steroid metabolism during development in the normal and hypogonadal mouse. , 1988, The Journal of endocrinology.

[17]  G. Shaw,et al.  Primary genetic control of somatic sexual differentiation in a mammal , 1988, Nature.

[18]  A. Borut,et al.  Metabolic pathways for androstanediol formation in immature rat testis microsomes. , 1987, Biochimica et biophysica acta.

[19]  G. Stone,et al.  Peripheral androgen levels in the male brush-tail possum (Trichosurus vulpecula). , 1985, The Journal of endocrinology.

[20]  G. Stone,et al.  Some effects of breeding season and castration on the prostate and epididymis of the brushtail possum, Trichosurus vulpecula. , 1985, Australian journal of biological sciences.

[21]  D. J. Chase,et al.  Changes in Leydig cell function during sexual maturation in the mouse. , 1983, Biology of reproduction.

[22]  Jean D. Wilson,et al.  Inhibition of steroid 5α-reductase from human skin fibroblasts by 17β-N, N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one , 1982 .

[23]  F. Labrie,et al.  Increased testicular 5α-androstane-3α, 17β-diol formation induced by treatment with [D-Ser(TBU)6, des-Gly-NH210]LHRH ethylamide in the rat , 1980, Steroids.

[24]  C. Desjardins,et al.  Testicular maturation in the rabbit: secretion of testosterone, dihydrotestosterone, 5alpha-androstan-3alpha, 17beta-diol and 5alpha-androstan-3beta, 17beta-diol by perfused rabbit testes-epididymides and spermatogenesis. , 1978, Biology of reproduction.

[25]  W. H. Moger.  Serum 5alpha-androstane-3alpha,17beta-diol, androsterone, and testosterone concentrations in the male rat. Influence of age and gonadotropin stimulation. , 1977, Endocrinology.

[26]  K. Matsumoto,et al.  Progesterone metabolism in vitro by rabbit testes at different stages of development. , 1976, Endocrinology.

[27]  K. Matsumoto,et al.  Progesterone metabolism in vitro by mouse testes at different stages of development. , 1974, Endocrinology.

[28]  J. Wilson,et al.  Partial characterization of the nuclear reduced nicotinamide adenine dinucleotide phosphate: delta 4-3-ketosteroid 5 alpha-oxidoreductase of rat prostate. , 1971, The Journal of biological chemistry.