A number of enzymes possessing 17beta-hydroxysteroid dehydrogenase/17-ketosteroid reductase (17HSD/KSR) activities have been described and cloned, but their nomenclature needs specification. To clarify the present situation, descriptions of the eight cloned 17HSD/KSRs are given and guidelines for the classification of novel 17HSD/KSR enzymes are presented.
H Peltoketo, V Luu-The, J Simard, and J Adamski
G. Pelletier, C. Labrie, J. Simard, M. Duval, M. G. Martinoli, H. Zhao, and F. Labrie
Prostatic steroid-binding protein (PBP) is the most abundant protein synthesized in the rat ventral prostate. The protein is under strict androgenic control and is made of two subunits containing the polypeptides Cl, C2 and C3. Using an 35S-labelled cDNA probe, we have used quantitative in-situ hybridization to assess the regulation of polypeptide Cl mRNA levels by sex steroids in the adult male rat. Densitometric quantification of autoradiographic hybridization signals revealed that a significant decrease in Cl mRNA levels could be detected 5 h after castration. Levels of Cl mRNA decreased by 50% 2·5 days after castration, while undetectable levels were reached within 7 days. Administration of the potent androgen 5α-dihydrotestosterone to castrated rats caused a progressive increase in Cl mRNA levels which became significant 5 h after the first injection, while prolonged treatment, for 3 and 7 days, caused 50 and 100% reversals respectively of the effect of castration on Cl mRNA levels. Similar results were obtained by dot-blot hybridization using the same 32P-labelled cDNA probe, thus confirming the specificity and quantification achieved by in-situ hybridization. Administration of oestradiol-17β to orchiectomized adult rats for 14 days had no effect on steady-state Cl mRNA levels. Progesterone, on the other hand, at the dose used (2 mg twice daily) caused a marked increase in Cl mRNA levels, measured by in-situ hybridization, which was completely reversed by concomitant administration of the pure antiandrogen flutamide.
The present data clearly demonstrate that the expression of PBP Cl peptide mRNA is under strict androgenic control and is a very sensitive and specific parameter of androgenic activity. They also indicate that quantitative in-situ hybridization is a powerful, sensitive and most efficient tool to study the regulation of gene expression while, in addition, providing precise information about the site of mRNA localization as well as information about the histology of the tissue, particularly the heterogeneous nature of the acinar response to androgenic stimulation and deprivation.
F Labrie, V Luu-The, SX Lin, J Simard, C Labrie, M El-Alfy, G Pelletier, and A Belanger
In women and men, an important proportion of estrogens and androgens are synthesized locally at their site of action in peripheral target tissues. This new field of endocrinology has been called intracrinology. In postmenopausal women, 100% of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while, in adult men, approximately 50% of androgens are made locally in intracrine target tissues. The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17beta-hydroxysteroid dehydrogenases (17 beta-HSDs) while different 17 beta-HSDs inactivate these steroids in the same cell where synthesis takes place. To date, seven human 17 beta-HSDs have been cloned, sequenced and characterized. The 17 beta-HSDs provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.