Review
Epitestosterone

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Abstract

Epitestosterone has been identified as a natural component of biological fluids of several mammals including man. For a long time it was believed that it is a metabolite without any hormonal activity and without any marked relationship to the hormonal state in health and disease. Neither the biosynthetic pathway nor the site of its formation in man have been unequivocally confirmed to date. It apparently parallels the formation of testosterone (T), but on the other hand its concentration is not influenced by exogenous administration of testosterone. This fact creates the basis of the present doping control of testosterone abuse. In 1989 an observation was presented in a dermatological study that epitestosterone exerts an effect counteracting the action of testosterone on flank organ of Syrian hamster. Further studies showed that a complex action consisting of competitive binding of epitestosterone to androgen receptor, of inhibition of testosterone biosynthesis and its reduction to dihydrotestosterone and of antigonadotropic activity could be demonstrated in rat, mice and human tissues. It can be presumed that epitestosterone as a natural hormone can contribute to the regulation of such androgen dependent events as, e.g. the control of prostate growth or body hair distribution.

Introduction

Epitestosterone (17α-hydroxy-4-androsten-3-one) is a naturally occurring epimer of testosterone (T). Clark and Kochakian [15] reported it for the first time in 1947 as an androgen metabolite on incubation with rabbit liver slices. However, the question regarding its origin and potential physiological role are not yet fully answered.

Section snippets

Occurrence of epitestosterone

Epitestosterone was recognized as a normal constituent of mares’ follicular fluid and bovine testes (see [24]). Similarly, follicular fluid from preovulatory follicles in women with stimulated cycles contains high concentration of epitestosterone [20]. Epitestosterone accumulation has been demonstrated in mammary cyst fluid [7] and in human prostate [35].

Curiously, epitestosterone is also a naturally occurring fytosteroid, in the pollen of pine Pinus silvestris [56].

Epitestosterone is formed

Epitestosterone in human under various conditions

For the determination of epitestosterone in human urine fluorimetric methods [36], [71], gas chromatography [21], gas chromatography/mass spectrometry [22], [43], [57] and radioimmunoassay [8] were elaborated. The latter method was also applied to the determination of epitestosterone in plasma. Plasma concentrations were first reported by Bı́lek et al. [8]. Recent data on age dependent plasma concentration of epitestosterone were reported by Lapčı́k et al. [45] and Havlı́ková et al. [32] as

Epitestosterone as a tool for antidoping control

Epitestosterone in the urine has attracted the attention as a reference substance in the doping control of testosterone abuse [22]. The nearly constant ratio of urinary testosterone to epitestosterone (1.1−1.5±1.0, range 0.03–4.9) in adults (see [43]) became the basis of the method of detection of exogenously administered testosterone, since epitestosterone does not originate from testosterone in significant amounts in the human. The maximum permissible testosterone to epitestosterone arbitrary

Origin and biosynthesis

In anima1 species (such as rabbit, guinea pig or mouse), which dispose high activity of 17α-hydroxysteroid oxidoreductase, a substantial proportion of epitestosterone originates from simple interconversion of testosterone to androstenedione and thereafter to epitestosterone. The interconversion is not only species but also organ specific, e.g. mouse kidney but not liver produces epitestosterone from androgen precursors [2]. No interconversion of testosterone and epitestosterone was observed in

The metabolism of epitestosterone

Little is known about the metabolism of epitestosterone, especially in the human. In human term placenta epitestosterone could be aromatized to estradiol-17α [33]. In normal men injected with labelled epitestosterone approximately 50% of the injected radioactivity was recovered as unchanged epitestosterone, whereas etiocholanolone plus androsterone represented only 2%, while 5β- and 5α-androstane-3α,17α-diols accounted for about 5%. Epitestosterone is poorly metabolized in man and it is not

Biological activity of epitestosterone

It has been believed that epitestosterone is virtually devoid of any biological activity; especially as no androgenic action could be demonstrated [23]. A marginal note existed indicating that epitestosterone is an inhibitor of 5α-reductase [49]. In 1965 Kincl et al. [41] injected epitestosterone, as well as several other androgens, estrogens and anabolic steroids, into 5 days old male and female rats and evaluated the steroid in vivo action on gonads at the age of 45 days. Epitestosterone was

Acknowledgements

This study was supported by research project 000000023761 of the Ministry of Health of the Czech Republic.

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