title: Regulation of the 3 beta-hydroxysteroid dehydrogenase activity in tissue fragments and microsomes from human term placenta: kinetic analysis and inhibition by steroids.
abstract: The effects of 50 microM of progesterone (P4), estradiol (E2), estrone (E1), estriol (E3), dehydroepiandrosterone (DHIA), androstenedione (delta 4) and testosterone (T) on the bioconversion of [3H]pregnenolone (6 nM) to [3H]P4 were investigated by incubating 200 mg of tissue fragments as well as equivalent aliquots of microsomes from human term placenta during 30 min. All the steroids assayed, except E3, significantly inhibited the [3H]P4 formation in a microsome incubation system with respect to the control assay (P less than 0.001). Conversely in a tissue incubation system. P4, E1 as well as E3 had no effect on [3H]pregnenolone bioconversion while E2 slightly decreased the [3H]P4 formation (P less than 0.05) compared with the control. A significant inhibition was observed in this system with the other steroids (P less than 0.001). To investigate these apparent different results of inhibition-noninhibition of the same steroids irrespective of the system of incubation used, the effects of P4, E2 and T on 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) activity were studied in tissue fragments and microsomes in kinetic terms. The results found indicate that these steroids inhibited in a competitive fashion the 3 beta-HSD activity in both systems. The different Ki values found in tissue fragments and microsomes respectively for P4 (1.8 microM vs 0.5 microM), E2 (2.3 microM vs 0.6 microM) and T (0.25 microM vs 0.3 microM) explain the bioconversion results obtained in presence of 50 microM of the same steroids. These results include inhibition of [3H]P4 formation by T in tissue fragments as well as in microsomes whereas P4 and E2 inhibited the [3H]P4 formation only in microsomes. Furthermore, the comparison of these Ki values with the available data of intraplacental and circulating concentrations of the same steroids in human term pregnancy suggest that only P4 would be expected to cause marked 3 beta-HSD inhibition in physiological conditions.
authors.affiliation: Departamento de Bioquímica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: S G
authors.initials: SG
authors.lastname: Raimondi
authors.forename: N S
authors.initials: NS
authors.lastname: Olivier
authors.forename: L C
authors.initials: LC
authors.lastname: Patrito
authors.forename: A
authors.initials: A
authors.lastname: Flury
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000735:Androstenedione / Q000494:pharmacology; D001667:Binding, Competitive; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D004970:Estrone / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010920:Placenta / Q000201:enzymology* / Q000648:ultrastructure; D011247:Pregnancy; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D012739:Gonadal Steroid Hormones; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol; D011284:Pregnenolone; D015096:3-Hydroxysteroid Dehydrogenases; D004964:Estriol