J. Steroid Biochem. Molec. BioL Vol.41, No. 3-8, pp. 597--603,1992 0960-0760/92$5.00+ 0.00 Printed in Great Britain.All rights reserved Copyright© 1992Pergamon Pressplc DISTRIBUTION OF 17fl-HYDROXYSTEROID DEHYDROGENASE GENE EXPRESSION AND ACTIVITY IN RAT AND HUMAN TISSUES C. MARTEL,E. RH~AUME, M. TAKAHASH1, C. TRUDEL,J. COUi~T, V. Luu-THE, J. SIMARD and F. LABRIE* MRC Group in Molecular Endocrinology, CHUL Research Center and Laval University, Quebec G1V 4G2, Canada Summary--The interconversion of estrone (Et) and 17fl-estradiol (E2), androstenedione (4-ene-dione) and testosterone (T), as well as dehydroepiandrosterone and androst-5-ene- 3fl,17fl-diol is catalyzed by 17fl-hydroxysteroid dehydrogenase (17fl-HSD). The enzyme 17fl-HSD thus plays an essential role in the formation of all active androgens and estrogens in gonadal as well as extragonadal tissues. The present study investigates the tissue distribution of 17fl-HSD activity in the male and female rat as well as in some human tissues and the distribution of 17fl-HSD mRNA in some human tissues. Enzymatic activity was measured using 14C-labeled El, E2, 4-ene-dione and T as substrates. Such enzymatic activity was demonstrated in all 17 rat tissues examined for both androgenic and estrogenic substrates. While the liver had the highest level of 17fl-HSD activity, low but significant levels of E 2 as well as T formation were found in rat brain, heart, pancreas and thymus. The oxidative pathway (E 2 ~ El, T ~4-ene-dione) was favored over the reverse reaction in almost all rat tissues while in the human, almost equal rates were found in most of the 15 tissues examined. The widespread distribution of 17fl-HSD in rat and human tissues clearly indicates the importance of this enzyme in peripheral sex steroid formation or intracrinology. INTRODUCTION It is well recognized that sex steroids can be synthesized in extragonadal tissue from circulat- ing precursors and that, furthermore, the trans- formation of biologically active steroids to inactive or weaker compounds is an important mechanism regulating the tissue levels of bio- active hormones[I-3]. It is thus of major importance to gain further information on the enzymatic systems responsible for the formation of active sex steroids in peripheral target tissues, especially on 17fl-hydroxysteroid dehydrogen- ase (17fl-HSD), the key enzyme which syn- thesizes androst-5-ene-3fl,17fl-diol (5-ene-diol) from dehydroepiandrosterone (DHEA), testos- terone (T) from androstenedione (4-ene-dione) and 17fl-estradiol (E2) from estrone (El). The interconversion of E l and E2 has been demonstrated in various human tissues, includ- ing the placenta [4], testis [4, 5], endometrium [6], vaginal mucosa [7], lung [8], liver [9], ileum Proceedings of the lOth International Symposium of the Journal of Steroid Biochemistry and Molecular Biology, Recent Advances in Steroid Biochemistry and Molecular Biology, Paris, France, 26-29 May 1991. *To whom correspondence should be addressed. [5], adipose tissue [10], skin [7], red blood cells [11], breast cancer cells [12] and prostatic cancer cells[13]. The presence of 17fl-HSD has also been demonstrated in vitro in a number of animal tissues, including the bovine placenta [14], porcine endometrium [15], rat lung [16] and a large series of Balb/c mouse tissues [17]. Most studies, however, have been performed using E t and E 2 as substrates and there are some data which suggest the existence of different enzymes having 17fl-HSD activity. Firstly, in human 17fl-HSD deficiency, the conversion of 4-ene-dione into testosterone is usually more impaired than the conversion of E l into E 2 [18]. Moreover, in vitro studies have shown a greater specificity of some enzyme preparations for estrogens while other preparations are more specific for androgens. For example, tissue from normal human follicular or luteal phase ovaries has low 17fl-HSD activity when 4-ene-dione or testosterone is used as substrate [19]. In order to obtain further information about estrogenic as well as androgenic 17fl-HSD, we have measured 17fl-HSD activity in a series of male and female rat tissues as well as in some human tissues using El, E2, 4-ene-dione and T as substrates. We report the widespread distribution of 597