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The enzymes, Δ45α-reductase, 3α- and 3β-hydroxysteroid oxidoreductases are present in the immature rat testis and account for its ability to produce saturated steroids from androstenedione and testosterone (Stylianou, Forchielli & Dorfman, 1961; Nayfeh, Barefoot & Baggett, 1966). Progesterone is converted to saturated C19-steroids by the immature rat testis in vitro (Steinberger & Ficher, 1969). It is assumed that androstenedione and testosterone are obligatory intermediates in their synthesis. Since it is known that 4,5-unsaturated C21-steroids are reduced in the rat testis (Bell, Vinson & Lacy, 1971) it was of interest to know whether saturated C21-steroids might also be precursors of saturated C19-steroids. To test this possibility [4-14C]5α-pregnane-3,20-dione was incubated in vitro with testicular tissue from sexually immature rats, and C19-steroids were sought among the products.
[4-14C]5α-Pregnane-3,20-dione was prepared by hydrogenation of 16 nmol (1 μCi)
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SUMMARY
A virilizing interstitial cell tumour and the attached testicular tissue from a 4-year-old boy were incubated in vitro with [7α-3H]pregnenolone and [4-14C]progesterone, or [4-14C]androstenedione and [7α-3H]5α-dihydrotestosterone. Ring A saturated steroids were produced from 4-ene precursors by the prepubertal testis, but this tissue was unable to convert pregnenolone or progesterone to 17α-hydroxylated C21 steroids, or to C19 steroids.
The virilizing interstitial cell tumour metabolized pregnenolone and progesterone to 17α-hydroxyprogesterone, androstenedione and testosterone. In addition, dehydroepiandrosterone was detected as a product of pregnenolone. The tumour lacked 4-ene-5α-steroid reductase activity.
5α-Dihydrotestosterone was metabolized to 5α-androstane-3,17-dione, androsterone, isoandrosterone, 5a-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol in both the normal and tumour tissue.
The significance of these metabolic pathways is discussed.
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The syndrome of testicular feminization may occur in complete or incomplete forms, the latter being characterized by varying degrees of virilism. In the complete form, plasma concentrations of testosterone and 5α-dihydrotestosterone are usually in or above the normal male range although the metabolic clearance rates of the steroids are similar to those of the normal female and lower than those of the normal male (Tremblay, Kowarski, Park & Migeon, 1972).
The formation in vitro of androstenedione and testosterone by gonads from such subjects has been demonstrated (Griffiths, Grant & Whyte, 1963; Neher & Kahnt, 1966; Charreau & Villee, 1968), but although the formation of 5α-reduced steroids has been inferred (Tremblay et al. 1972), their biosynthesis has not previously been recorded. In view of the changes in steroid 4-ene-5α-reductase activity at puberty in animal testes (Steinberger & Ficher, 1969), the production and metabolism of C19-reduced steroids in gonads from
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SUMMARY
The metabolism of [7α-3H]dehydroepiandrosterone (DHA) and [4-14C] androstenedione in vitro was investigated in 30-day-old (prepubertal) and adult rat testicular tissue in the presence of cyanoketosteroid, a 5-ene-3β-hydroxysteroid oxidoreductase inhibitor.
Whereas both substrates were converted to 5α-reduced steroids by the prepubertal testis, 4-ene-steroid-5α-reductase activity was negligible in the adult gland. Cyanoketosteroid prevented the formation of 5α-reduced steroids from DHA by the prepubertal testis indicating testosterone and androstenedione as intermediates in their production.
