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The "Puberty" of the Rat Liver. II. Permanent Changes in Steroid Metabolizing Enzymes After Treatment with a Single Injection of Testosterone Propionate at Birth¹

Rega Instltuut, Laboratorium voor Experimented Geneeskunde, en Kliniek voor Inwendige Geneeskunde, Academisch Ziekenhuis St Rafaël, Leuven, Belgium

This work was supported by Grant 853 of the "Nationaal Fonds voor Geneeskundig Wetenschappelijk Onderzoek."

Abstract

Rats of both sexes were spayed and injected with either 50 or 500 µg of testosterone propionate (TP) on their first day of life or later. Four to 5 months afterward the animals were sacrificed. Liver homogenates or microsomes were incubated with tritium labeled cortisol, tetrahydrocortisol, progesterone and testosterone. Spayed female rats treated with 500 µg or even with 50 µg TP on their first day of life as well as with 500 µg TP on the 6th day developed and maintained during adult life a pattern of steroid metabolism characteristic of male adult animals: the ⁴-3-keto reduction in crude liver homogenate to allo-tetrahydrocortisol and the ⁴-5-reduction in liver microsomes to allodihydrotestosterone and -progesterone had significantly decreased as compared with spayed control animals. On the other hand, the reduction of cortisol to 3β and 20β-hydroxy metabolites as well as the 20-keto reduction of tetrahydrocortisol to β-cortol had been increased. When female rats castrated in neonatal life were treated with TP (up to 10 daily injections of 500 µg) in their adult life, a typical masculine pattern was induced immediately after the final treatment. However, within a time interval of 2 months, these effects completely disappeared. In male rats a single injection of 500 µg of TP at birth almost entirely prevented the differentiation of the feminine type of steroid metabolism found after castration performed the same day. An injection of 50 ng of TP had a similar though less explicit effect. It can be concluded that in neonatal life testosterone opens the possibility for permanent activation or depression at puberty of certain enzymes in the liver. During adult life, however, the effect of testosterone on these enzymes is only temporary. (Endocrinology 83: 791,1968)

Footnotes

¹ The following abbreviations are used: cortisol-1,2-³H: tritium labeled cortisol; testosterone-1,2-³H: tritium labeled testosterone; progesterone-16-³H: tritium labeled progesterone; allo-dihydrocortisol: 11β,17,21-trihydroxy-5-pregnane-3,20-dione; allo-tetrahydrocortisol: 3,11β,17,21-tetrahydroxy-5-pregnan-20-one; 3β-allo-tetrahydrocortisol: 3β,11β,17,21-tetrahydroxy-5β-pregnan-20-one; tetrahydrocortisol: 3,11β,17,21-tetrahydroxy-5β-pregnan-20-one; 20β-hydroxy cortisol: 11β,17,20β,21-tetrahydroxypregn-4-en-3-one: cortols: 3,11β,17,20β,21-pentahydroxy-5β-pregnane, 3β,11β,17,20β,21-pentahydroxy-5-pregnane and 3,11β,17,20β,21-pentahydroxy-5-pregnane; allodihydrotestosterone: 17β-hydroxy-5-androstan-3-one; allo-dihydroprogesterone: 5-pregnane-3,20-dione; TP: testosterone propionate: 17β-propionate-androst-4-ene-3-one.

² Aspirant of the "Nationaal Fonds voor Wetenschappelijk Onderzoek."

Received March 26, 1968.

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