Rapid and intensive conversion of 5α-androstane-3α,17β-diol into 5α-dihyorotestosterone in the male rat anterior pituitary: in vivo and in vitro studies

Pilven, Antoine; Thieulant, Marie-Lise; Ducouret, B.; Samperez, S; Jouan, P

doi:10.1016/0039-128x(76)90045-3

Cited by 25 publications

(8 citation statements)

References 30 publications

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“…Gay (1975) showed that this infused DHT was converted to serum 5a-androstane-3a, 17/3-diol, which Pilven, Thieulant, Ducouret, Samperez and Jouan (1976) showed to be rapidly and intensively converted to DHT in the anterior pituitary. Thus, there is a potential mechanism by which DHT may cause increased pituitary DHT concentrations without increasing blood levels.…”

Section: Discussionmentioning

confidence: 97%

Positive Feedback Effect of Dihydrotestosterone on Follicle-Stimulating Hormone Secretion in the Male Rat: Implications and a Possible Relation to the Onset of Puberty

Jc¹,

Nh²,

J³

1981

Horm Metab Res

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Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were measured in serum of adult male rats after 6 days of constant subcutaneous infusion of varying levels of dihydrotestosterone (DHT). Doses from one-half up to the normal "blood production rate" of DHT produced a selective stimulation of serum FSH, but not LH, levels. Higher levels suppressed FSH, LH, and testosterone. Despite the presence of much higher levels of testosterone in blood, the augmentation of FSH secretion indicated in these studies suggests that DHT may have an important role in regulatory systems for gonadotropins.

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Section: Discussionmentioning

confidence: 97%

Positive Feedback Effect of Dihydrotestosterone on Follicle-Stimulating Hormone Secretion in the Male Rat: Implications and a Possible Relation to the Onset of Puberty

Jc¹,

Nh²,

J³

1981

Horm Metab Res

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“…Third, in the brain 5␣-adiol inhibits the ␥-aminobutyric acid receptor, a system that may or may not function in other tissues (26). Finally, 5␣-adiol may act by back conversion to DHT because a large fraction of radioactive 5␣-adiol is recovered in the form of DHT in putative sites of androgen action (27,28) and because DHT is formed from both testosterone and 5␣-adiol in the prostates of the dog (29) and rat (27). The metabolic studies reported here indicate that the urogenital sinus and urogenital tubercle of the developing tammar convert 5␣-adiol to DHT, which then can act via the androgen receptor (1).…”

Section: Discussionmentioning

confidence: 99%

Prostate formation in a marsupial is mediated by the testicular androgen 5α-androstane-3α,17β-diol

Shaw

Renfree

Leihy

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

101

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Development of the male urogenital tract in mammals is mediated by testicular androgens. It has been tacitly assumed that testosterone acts through its intracellular metabolite dihydrotestosterone (DHT) to mediate this process, but levels of these androgens are not sexually dimorphic in plasma at the time of prostate development. Here we show that the 3␣-reduced derivative of DHT, 5␣-androstane-3␣,17␤-diol (5␣-adiol), is formed in testes of tammar wallaby pouch young and is higher in male than in female plasma in this species during early sexual differentiation. Administration of 5␣-adiol caused formation of prostatic buds in female wallaby pouch young, and in tissue minces of urogenital sinus and urogenital tubercle radioactive 5␣-adiol was converted to DHT, suggesting that circulating 5␣-adiol acts through DHT in target tissues. We conclude that circulating 5␣-adiol is a key hormone in male development. I n all mammalian species testicular androgens control three aspects of male phenotypic development-conversion of the wolffian ducts into the epididymis, vas deferens, and seminal vesicles; formation of the male urethra and prostate; and formation of the phallus (1). Studies in animals and humans with mutations in the genes that encode the androgen receptor or steroid 5␣-reductase 2 indicate that testosterone virilizes the wolffian ducts and that 5␣-reduced androgens are essential for formation of the prostate and phallus (1). Because virilization occurs during early fetal development in eutherian mammals, it has not been possible to measure androgens in the circulation when virilization begins.Marsupial mammals offer an advantage for studying male phenotypic development, which takes place after birth when the young are easily accessible in the pouch and over a longer period than in the eutherian, so that it is possible to study the various aspects of phenotypic development individually (2). Virilization of the urogenital tract in the male marsupial pouch young is similar to that in eutherian fetuses, except that formation of the scrotum in marsupials is androgen-independent (2-6). This process has been examined in detail in one marsupial species, the tammar wallaby, Macropus eugenii, in which formation of the prostate begins in the urogenital sinus at around day 20 postpartum (5), whereas virilization of the penis commences around day 100 (6). Testosterone concentrations in the testes increase before prostate formation begins (7), and prostate development can be prevented by administration of the steroid 5␣-reductase inhibitor finasteride (8), which blocks the formation of dihydrotestosterone (DHT), or of the androgen receptor inhibitor flutamide (9), which prevents the actions of both testosterone and DHT. Administration of large amounts of testosterone (5) or transplantation of testes to female pouch young (10) causes prostate development, whereas castration of 10-day-old male pouch young prevents formation of the prostate and penis (10).Despite the wealth of evidence for a crucial role of 5␣-reduced androge...

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“…Due to its low binding affinity to the AR with K d = 10 −6 M [11], it has been widely accepted that 3␣-diol must first be oxidized to 5␣-DHT by 3␣-HSDs before exerting its androgenic functions [12]; thus this reaction represents an alternative pathway for regulating steady-state levels of 5␣-DHT in androgen target tissues. This hypothesis has been supported by the formation and accumulation of 5␣-DHT in androgen target tissues including the prostate following 3␣-diol administration in various animal models including dog [12] and rat [13,14]. It has further been shown that the AR antagonist, flutamide, prevents 3␣-diol from virilizing the urogenital sinus of the tammar wallaby, suggesting that 3␣-diol may be a precursor for 5␣-DHT, which is responsible for virilizing in the wallaby [10].…”

Section: Introductionmentioning

confidence: 88%

Partitioning of 5α-dihydrotestosterone and 5α-androstane-3α, 17β-diol activated pathways for stimulating human prostate cancer LNCaP cell proliferation

Nunlist

Dozmorov

Tang

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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Rapid and intensive conversion of 5α-androstane-3α,17β-diol into 5α-dihyorotestosterone in the male rat anterior pituitary: in vivo and in vitro studies

Cited by 25 publications

References 30 publications

Positive Feedback Effect of Dihydrotestosterone on Follicle-Stimulating Hormone Secretion in the Male Rat: Implications and a Possible Relation to the Onset of Puberty

Positive Feedback Effect of Dihydrotestosterone on Follicle-Stimulating Hormone Secretion in the Male Rat: Implications and a Possible Relation to the Onset of Puberty

Prostate formation in a marsupial is mediated by the testicular androgen 5α-androstane-3α,17β-diol

Partitioning of 5α-dihydrotestosterone and 5α-androstane-3α, 17β-diol activated pathways for stimulating human prostate cancer LNCaP cell proliferation

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