The Intranuclear Metabolism of Testosterone in the Accessory Organs of Reproduction

Wilson, Jean D.; Gloyna, Robert E.

doi:10.1016/b978-0-12-571126-5.50012-1

Cited by 141 publications

(85 citation statements)

References 18 publications

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“…The active hormone is probably testosterone, since 5␣ reductase is not present in muscle (Wilson and Gloyna, 1970). Two older studies (Griggs et al, 1989;Forbes et al, 1992) have been supplemented by several recent findings demonstrating increased lean body mass, muscle protein synthesis, and/or positive nitrogen balance in normal men after high doses of AAS (Bhasin et al, 1996;Ferrando et al, 1998;Sheffield-Moore et al, 1999;Strawford et al, 1999;see also review in Sheffield-Moore, 2000).…”

Section: A Role Of Suprapharmacologic Dosesmentioning

confidence: 99%

Anabolic Steroids

Kuhn¹

2002

Recent Progress in Hormone Research

195

185

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The term "anabolic steroids" refers to testosterone derivatives that are used either clinically or by athletes for their anabolic properties. However, scientists have questioned the anabolic effects of testosterone and its derivatives in normal men for decades. Most scientists concluded that anabolic steroids do not increase muscle size or strength in people with normal gonadal function and have discounted positive results as unduly influenced by positive expectations of athletes, inferior experimental design, or poor data analysis. There has been a tremendous disconnect between the conviction of athletes that these drugs are effective and the conviction of scientists that they aren't. In part, this disconnect results from the completely different dose regimens used by scientists to document the correction of deficiency states and by athletes striving to optimize athletic performance. Recently, careful scientific study of suprapharmacologic doses in clinical settings -including aging, human immunodeficiency virus, and other disease states -supports the efficacy of these regimens. However, the mechanism by which these doses act remains unclear."Anabolism" is defined as any state in which nitrogen is differentially retained in lean body mass, either through stimulation of protein synthesis and/or decreased breakdown of protein anywhere in the body. Testosterone, the main gonadal steroid in males, has marked anabolic effects in addition to its effects on reproduction that are easily observed in developing boys and when hypogonadal men receive testosterone as replacement therapy. However, its efficacy in normal men, as during its use in athletes or in clinical situations in which men are eugonadal, has been debated. A growing literature suggests that use of suprapharmacologic doses can, indeed, be anabolic in certain situations; however, the clear identification of these situations and the mechanism by which anabolic effects occur are unclear. Furthermore, the pharmacology of "anabolism" is in its infancy: no drugs currently available are "purely" anabolic but all possess androgenic properties as well. The present review briefly recapitulates the historic literature about the androgenic/anabolic steroids and describes literature supporting the anabolic activity of these drugs in normal people, focusing on the use of suprapharmacologic doses by athletes and clinicians to achieve anabolic effects in normal humans. We will present the emerging literature that is beginning to explore more specific mechanisms that might mediate the effects of suprapharmacologic regimens. The terms anabolic/androgenic steroids will be used throughout to reflect the combined actions of all drugs that are currently available.

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Section: A Role Of Suprapharmacologic Dosesmentioning

confidence: 99%

Anabolic Steroids

Kuhn¹

2002

Recent Progress in Hormone Research

195

185

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“…During the past few years increased attention has been focused on dihydrotestosterone (DHT)1 as the result of the discovery that testosterone (T) is converted mainly into dihydrotestosterone at the site of its target tissues (1)(2) and the fact that part of the biological actions of testosterone could be produced by dihydrotestosterone (3). More recently, it has been shown that the plasma concentration of dihydrotestosterone is higher in males than in females, and in both sexes its concentration is far lower than testosterone (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism

Saez¹,

Forest²,

Morera³

et al. 1972

J. Clin. Invest.

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A B S T R A C T The metabolic clearance rate (MCR) and blood production rate (BP) of testosterone (T) and dihydrotestosterone (DHT), the conversion of plasma testosterone to plasma dihydrotestosterone, and the renal clearance of androstenedione, testosterone, and dihydrotestosterone have been studied in man. In eight normal men, the MCRT (516±108 [SD] liters/m/day) was significantly greater than the MCRDIT (391±71 [SD] liters/m'/day). In seven females, the MCRT (304±53 [SD] liters/m'/day) was also greater than the MCRDET (209±45 [SD] liters/ m2/day) and both values were less than their respective values in men (P <0.001). In men the conversion of testosterone into dihydrotestosterone at 2.8±0.3% (SD) was greater than that found in females, 1.56±0.5% (SD) (P < 0.001). In five pregnant females the MCRT (192± 36 [SD] liters/m/day), the MCRDHT (89±30 [SD] liters/ m'/day) and the conversion of testosterone into dihydrotestosterone (0.72±0.15%) (SD) were significantly less than the values found in nonpregnant women. In five females with hyperthyroidism, the MCR for testosterone and dihydrotestosterone were similar to those observed in pregnant females, but the conversion of testosterone into dihydrotestosterone (2.78±1.7%) (SD) was greater, and similar to that found in men. In men the production of dihydrotestosterone was 0.39±0.1 (SD) mg/day, 50% being derived from the transformation of plasma testosterone. In women the production of DHT was 0.05± 0.028 (SD) mg/day, only 10% coming from testosterone. During pregnancy, the production of testosterone and dihydrotestosterone are similar to that in normal women. In three patients with testicular feminization syndrome A preliminary report of this work was presented at the 52nd Meeting of the Endocrine Society, June 1970.Received for publication 24 August 1971 and in revised form 20 December 1971. (an adult with hyperthyroidism and two children) these two MCRs were greatly reduced compared to the normal females, but the conversion of testosterone into dihydrotestosterone was in the limits of normal male rangeIn the normal subjects the renal clearance of androstenedione was greater than that of testosterone and dihydrotestosterone. Less than 20% of the dihydrotestosterone and less than 10% of the androstenedione in the urine is derived from the plasma dihydrotestosterone and androstenedione.

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“…In the course of the same investigation we have also compared the stimulating potency of testosterone with that of 5a-dihydrotestosterone, an androgenic steroid to which testosterone is known to be converted in the male accessory organs (Bruchovsky & Wilson, 1968;Anderson & Liao, 1968;Wilson & Gloyna, 1970;Williams-Ashman & Reddi, 1971). We found that, when introduced directly into the seminal vesicle, dihydrotestosterone oenanthate was capable of promoting growth and formation of fructose and citric acid, but the magnitude of the effect was no more than that of a corresponding dose of testosterone oenan¬ thate.…”

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confidence: 99%