Some Aspects of Steroid Transformations in the Testes of Human Subjects and of Rats with Experimental Cryptorchidism or Feminisation

Abstract

The in vitro approach to the study of steroid biosynthesis yields information about the sequence of biochemical transformations which can occur in gonadal tissue and complements investigations in vivo. The current concept of steroid transformations in human testicular tissue is based upon studies performed under differing experimental conditions and the situation in healthy and pathological tissue is by no means established. In this short communication, representative results from two types of in vitro study will be described — experiments in which aliquots of the same tissue were incubated with the same isotopically labelled substrate for varying periods of time; and those in which the same tissue was incubated with several substrates for a constant time. In addition to a series of incubations of human testicular tissue, the rat testis was selected for comparative studies which could not have been performed in human subjects. The main feature of this work was the use of a variety of labelled steroid precursors in a series of replicate experiments which were performed under standardised conditions in three groups of rats-controls; experimental cryptorchidism; and after feminisation by the administration of the anti-androgen — Cyproterone — to the mother rats during pregnancy and to the newborn (as the acetate) during the first ten days of life. After extensive purification, evidence for the identity of the radiometabolites was obtained by gas-liquid chromatography and by recrystallisation to constant specific activity. The reproducibility of results obtained from replicate incubations permits general conclusions as to the extent of incorporation of radioactivity into the principal products and a tentative interpretation in terms of major enzymatic transformations. The results indicate an increase in 3β-ol-dehydrogenation, 17-hydroxylation and side-chain cleavage in the cryptorchid testes accompanied by a decrease in 17-ketosteroid reduction. On the other hand in the tests of the feminised animals there is evidence for impairment of both 17-hydroxylation and of the side-chain clearage of δ4-3-ketosteroid intermediaries. The results obtained in human and rat testes will be discussed with special reference to the capacity for the formation of testosterone and oestradiol-17β.