Reduction of 5α-Position of Testosterone in the Rat Ventral Prostate

Shimazaki, Jun; Matsushita, I; Furuya, Nobuo; Yamanaka, Hidetoshi; Shida, Keizo

doi:10.1507/endocrj1954.16.453

Cited by 48 publications

(22 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Estrogen (22) and luteotrophic hormone (23) have been shown to augment SPC surfactant production, and lung receptors for estrogen have been demonstrated (24). Specific androgen receptors have also been identified in both adult rat lung (25) and human fetal lung fibroblasts (26). In the human fetal lung the males have more androgen receptor activity than the females, reflecting the fact that androgens stimulate their own receptors (26).…”

Section: Discussionmentioning

confidence: 99%

“…Specific androgen receptors have also been identified in both adult rat lung (25) and human fetal lung fibroblasts (26). In the human fetal lung the males have more androgen receptor activity than the females, reflecting the fact that androgens stimulate their own receptors (26). Testosterone is activated locally to DHT in target cells by the enzyme 5a-reductase.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dihydrotestosterone Inhibits Fetal Rabbit Pulmonary Surfactant Production

Nielsen¹,

Zinman²,

Torday³

1982

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Males have a higher morbidity and mortality for neonatal respiratory distress syndrome (RDS) than females, and respond less well to hormone therapy designed to prevent RDS by stimulating fetal pulmonary surfactant production. We have shown that male fetuses exhibit delayed production of pulmonary surfactant. We tested the hypothesis that the sex difference in fetal pulmonary surfactant production is under hormonal control. Pulmonary surfactant was measured as the saturated phosphatidylcholine/sphingomyelin ratio (SPC/S) in the lung lavage of fetal rabbits at 26 d gestation. There was an association between the sex of neighboring fetuses and the SPC/S ratio of the female fetuses, such that with one or two male neighbors, respectively, females had decreasing SPC/ S ratios (P < 0.05). We injected dihydrotestosterone (DHT) into pregnant does from day 12 through day 26 of gestation in doses of 0.1, 1.0, 10, and 25 mg/d, and measured the SPC/S ratio in fetal lung lavage on day 26. In groups with the normal sex difference in fetal serum androgen levels (controls, 0.1 mg DHT/d) the normal sex difference in the SPC/S ratio was also present (females> males, P = 0.03). In the 1-mg/d group there was no sex difference in androgen levels and the sex difference in the SPC/S ratio was also eliminated as the female values were lowered to the male level. Higher doses of DHT (10, 25 mg/d) further reduced the SPC/S ratios. We injected the anti-androgen Flutamide (25 mg/d) from day 12 through day 26 of gestation. This treatment eliminated the normal sex difference in the lung lavage SPC/S ratio by increasing the male ratios to that of the females. We conclude that androgens inhibit fetal pulmonary surfactant production. An understanding of the mechanism of the sex difference in surfactant production

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dihydrotestosterone Inhibits Fetal Rabbit Pulmonary Surfactant Production

Nielsen¹,

Zinman²,

Torday³

1982

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The activity of 5 a-reductase, the enzyme that converts testosterone into dihydrotestosterone in the ventral prostate, is decreased after castration, but can be restored to non-castrated-animal or higher values by pharmacological doses of androgens (Shimazaki et al, 1969;Moore & Wilson, 1973). To determine whether the restoration of 5a-reductase activity is related to the nuclear accumulation of either dihydrotestosterone or androgen receptor, prostatic homogenates, prepared from 7-daycastrated rats that had been treated with dihydrotestosterone, were assayed for this enzyme.…”

Section: Effects Of Dose On the Intracellular Concentration Of Dihydrmentioning

confidence: 99%

“…Increases in the concentration of nuclear androgen receptors in the regenerating prostate occur as a consequence of androgenic stimulation of receptor synthesis as opposed to recycling of pre-existing androgen receptors (Van Doorn et al, 1976;. The restoration of 5a-reductase activity to values found in prostates from noncastrated rats is achieved in regenerating prostates after 4 days of treatment with androgen (Shimazaki et al, 1969), and is dose-dependent (Table 1). As with the growth-fraction data, there is a linear correlation (correlation coefficient 0.98) between the concentration of nuclear androgen receptor and 5a-reductase activity.…”

Section: Effects Of Dose On the Intracellular Concentration Of Dihydrmentioning

confidence: 99%

“…Specific responses in the ventral prostate, including the initiation of DNA synthesis and cell proliferation (Lesser & Bruchovsky, 1973), stimulation of 5a-reductase activity (Shimazaki et al, 1969) and the induction of secretory acid phosphatase , are elicited by different doses of dihydrotestosterone. In this context, cell proliferation is a dominant response, whereas the induction of secretory acid phosphatase, a marker of differentiation, is a subordinate one.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Radioimmunoassay measurements of nuclear dihydrotestosterone in rat prostate. Relationship to androgen receptors and androgen-regulated responses

Larminat¹,

Rennie²,

Bruchovsky³

1981

Biochemical Journal

View full text Add to dashboard Cite

The concentration of dihydrotestosterone was measured by radioimmunoassay in nuclear and cytoplasmic extracts from rat ventral prostates. In the regenerating prostates of castrated rats treated with dihydrotestosterone for 4 days, the nuclear concentration of this steroid increased from approx. 70nM to 800nM as a linear function of the injected dose, whereas the cytoplasmic concentration remained relatively constant (70-130nM). Isotope-exchange measurements of nuclear androgen receptors by using [3H]methyltrienolone indicated that, although the concentration of nuclear dihydrotestosterone was several-fold higher than the concentration of androgen receptors, they were logarithmically related. The recruitment of prostatic cells into the growth fraction and the stimulation of 5 a-reductase activity were more directly correlated to the nuclear concentration of androgen receptors than to the total nuclear concentration of dihydrotestosterone. Maximal restoration of a specific isoenzyme of acid phosphatase was achieved when approx. 2000 androgen receptors were present in the prostatic nuclei; higher concentrations of nuclear androgen receptors were associated with decreased amounts of this enzyme. Hence the results imply, first, that the total amount of dihydrotestosterone accumulated by nuclei is not a direct consequence of carrier-mediated transport by androgen receptors, and, secondly, that, whereas acid phosphatase may be differentially controlled by androgens in the regenerating prostate, increases in the amount of cell proliferation and 5a-reductase activity directly parallel increases in the nuclear concentration of androgen receptors.In the prostate, androgenic regulation of physiological functions and cellular growth is attributed largely to the formation, and subsequent binding to chromatin, of androgen-receptor complexes (King & Mainwaring, 1974 (Coffey, 1974;Rennie et al., 1975;Van Doorn et al., 1976). Although it has been postulated that androgen receptors are involved in the uptake and retention of dihydrotestosterone by target-cell * To whom correspondence should be addressed.Vol. 200 nuclei (Rennie & Bruchovsky, 1973;Bruchovsky et al., 1975a), a direct stoicheiometric relationship has not been demonstrated. When castrated rats are injected with radioactive androgen in the ventral prostate the concentration of radioisotope measured in nuclei exceeds that measured in the cytoplasm (Bruchovsky et al., 1975b). However, the concentration of androgen-receptor complexes recovered from the nuclei is insufficient to account for the nuclear influx of androgens if a mole-to-mole relationship is assumed. Furthermore, radioimmunoassay measurements of dihydrotestosterone in ventral prostates from non-castrated rats have indicated that only about 20% of the endogenous nuclear androgen is bound to androgen receptors (Bruchovsky et al., 1980). Whether the large nuclear concentration of non-receptor-bound dihydrotestosterone is achieved through a receptor mechanism or

show abstract

Male Sex Hormones, Analogs, and Antagonists

Brueggemeier

2010

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

The steroid testosterone is the major circulating sex hormone of the male and serves as the prototype for the androgens, the anabolic agents, and androgen antagonists. The endogenous androgens are biosynthesized from cholesterol in various tissues in the body; the majority of the circulating androgens are made in the testes under the stimulation of the gonadotropin luteinizing hormone ( LH ). The reduction of testosterone to dihydrotestosterone is necessary for the androgenic actions of testosterone in many androgen target tissues such as the prostate; the oxidation of testosterone by the enzyme aromatase produces estrogens. The androgenic actions of testosterone and dihydrotestosterone are due to their binding to the androgen receptor, followed by nuclear localization, dimerization of the receptor complex, and binding to a specific DNA sequence. This binding of the homodimer to the androgen response element leads to gene expression, stimulation or repression of the synthesis of new mRNA, and subsequent protein biosynthesis. The synthetic androgens and anabolics were prepared to impart oral activity to the androgen molecule, to separate the androgenic effects of testosterone from its anabolic effects, and to improve upon its biological activities. Novel nonsteroidal androgens, termed selective androgen receptor modulators, were developed to impart agonist activity in selective tissues. Drug preparations are used for the treatment of various androgen‐deficient diseases, for the therapy of diseases characterized by muscle wasting and protein catabolism, for postoperative adjuvant therapy, and for the treatment of certain hormone‐dependent cancers. The two major categories of androgen antagonists are the antiandrogens, which block interactions of androgens with the androgen receptor, and the inhibitors of androgen biosynthesis and metabolism. Such compounds have therapeutic potential in the treatment of acne, virilization in women, hyperplasia and neoplasia of the prostate, and baldness and male contraception.

show abstract

Reduction of 5α-Position of Testosterone in the Rat Ventral Prostate

Cited by 48 publications

References 9 publications

Dihydrotestosterone Inhibits Fetal Rabbit Pulmonary Surfactant Production

Dihydrotestosterone Inhibits Fetal Rabbit Pulmonary Surfactant Production

Radioimmunoassay measurements of nuclear dihydrotestosterone in rat prostate. Relationship to androgen receptors and androgen-regulated responses

Male Sex Hormones, Analogs, and Antagonists

Contact Info

Product

Resources

About