Estimating the Contribution of the Prostate to Blood Dihydrotestosterone

Toorians, Arno W. F. T.; Kelleher, Sharyn; Gooren, Louis; Jimenez, Mark; Handelsman, David J.

doi:10.1210/jc.2003-030521

Cited by 23 publications

(15 citation statements)

References 31 publications

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“…The clinical significance of plasma DHT is very limited because most DHT formed in peripheral tissue acts locally (12), only a limited fraction escaping to the circulation where DHT is strongly bound to SHBG, only 0.8% being free. Androstenedione and DHEA are loosely bound to albumin, the binding to SHBG being negligible; DHEAS on the other hand is relatively strongly bound to albumin (13).…”

Section: A Sex Steroids In the Systemic Circulationmentioning

confidence: 99%

The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications

2005

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Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum levels below the range for young men. Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established. In fact, minimal androgen requirements for elderly men remain poorly defined and are likely to vary between individuals. Consequently, borderline androgen deficiency cannot be reliably diagnosed in the elderly, and strict differentiation between "substitutive" and "pharmacological" androgen administration is not possible. To date, only a few hundred elderly men have received androgen therapy in the setting of a randomized, controlled study, and many of these men were not androgen deficient. Most consistent effects of treatment have been on body composition, but to date there is no evidence-based documentation of clinical benefits of androgen administration to elderly men with normal or moderately low serum testosterone in terms of diminished morbidity or of improved survival or quality of life. Until the long-term risk-benefit ratio for androgen administration to elderly is established in adequately powered trials of longer duration, androgen administration to elderly men should be reserved for the minority of elderly men who have both clear clinical symptoms of hypogonadism and frankly low serum testosterone levels.

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Section: A Sex Steroids In the Systemic Circulationmentioning

confidence: 99%

The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications

2005

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“…The conversion of T to the more potent androgen DHT by the enzyme 5α-reductase occurs in the testis and other tissues, including the prostate. Although the normal prostate has been reported not to contribute to the circulating levels of DHT (2), there may be a contribution by this organ in subjects with a hypertrophic prostate (3). Both T and DHT bind to the same androgen receptor (AR) with different affinities and apparently with different transcriptional activities.…”

Section: Introductionmentioning

confidence: 99%

Early effects of estrogen on the rat ventral prostate

García-Flórez

Oliveira

Carvalho

2005

Braz J Med Biol Res

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Complex interactions between androgen and estrogen (E2) regulate prostatic development and physiology. We analyzed the early effects of a high single dose of E2 (25 mg/kg body weight) and castration (separately or combined) on the adult 90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight, and the variation in the relative and absolute volume of tissue compartments and apoptotic indices were determined for 7 days. Castration and exogenous E2 markedly reduced ventral prostate weight (about 50% of the control), with a significant reduction in the epithelial compartment and increased stroma. The final volume of the epithelium was identical at day 7 for all treatments (58.5% of the control). However, E2 had an immediate effect, causing a reduction in epithelial volume as early as day 1. An increase in smooth muscle cell volume resulted from the concentration of these cells around the regressing epithelium. The treatments resulted in differential kinetics in epithelial cell apoptosis. Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells presenting signs of apoptosis, whereas E2 caused an immediate increase (observed on day 1) and a sustained (up to day 7) effect. E2 administration to castrated rats significantly increased the level of apoptosis by day 3, reaching 9% of the epithelial cells. The divergent kinetics between treatments resulted in the same levels of epithelial regression after 7 days (~30% of control). These results show that E2 has an immediate and possibly direct effect on the prostate, and anticipates epithelial cell death before reducing testosterone to levels as low as those of castrated rats. In addition, E2 and androgen deprivation apparently cause epithelial cell death by distinct and independent pathways.

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“…109 Prostate development remains rudimentary, 110 and sparse body hair without balding is characteristic. 116 Whereas genetic mutations disrupting type 2 5α-reductase produce disorders of urogenital sinus-derived tissues in men and mice, 117 genetic inactivation of type 1 5α-reductase includes no male phenotype in mice, and no mutations of the human type 1 enzyme have been reported. This amplification mechanism for androgen action was exploited in developing azasteroid 5α-reductase inhibitors.…”

Section: Metabolismmentioning

confidence: 99%