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Steroid Sulfohydrolase in Human Chorion and Decidua: Studies Using Pregnenolone Sulfate and Dehydroepiandrosterone Sulfate as Substrate

Department of Obstetrics and Gynecology, University of Alberta Edmonton, Alberta, Canada

Address requests for reprints to: Dr. B. F. Mitchell, Department of Obstetrics and Gynecology, 1D1 W.C. Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2R7.

This work was supported by grant MA7731 from the Medical Research Council of Canada.

Human chorion and decidua use pregnenolone sulfate (P₅S) and dehydroepiandrosterone sulfate (DHAS) as substrates for local estrogen and progesterone synthesis. We hypothesized that the local estrogen/progesterone ratio may influence contractility of the adjacent myometrium and hence effect the timing of parturition. Thus, we studied steroid sulfohydrolase activity for P₅S in these tissues and investigated the potential interaction of other steroids on the rates of hydrolysis of P₅S and DHAS. The enzyme was present in both tissues, predominantly in the microsomal fraction. With P₅S as substrate, the Michaelis-Menten constant (K_m) was similar in chorion (1.3 ± 0.2 µmol/L, mean ± SEM) and decidua (0.9 ± 0.1 µmol/L) but the maximum velocity (v_max) was significantly greater in chorion (2.6 ± 0.4 vs 1.1 ± 0.3 nmol/mg protein/15 min, P < 0.05). In both tissues there was a tendency towards greater activity in tissues obtained before labor compared to tissues obtained after spontaneous labor onset.

Using either DHAS or P₅S as substrate, there was significant inhibition of sulfohydrolase activity by other steroids at concentrations similar to those in late pregnancy fetal and maternal plasma. In microsomal preparations using DHAS as substrate, activity was inhibited by equimolar concentrations of estrone sulfate (E₁S, by 38 ± 2%), P₅S (by 74 ± 2%), and cholesterol sulfate (C₂₇S, by 38 ± 3%). With P₅S as substrate, equimolar concentrations of E₁S, DHAS, and C₂₇S caused inhibition of sulfohydrolase activity by 19 ± 5%, 16 ± 4%, and 18 ± 2%, respectively. These inhibitory effects also were observed using a tissue explant system with intact cells.

In kinetic inhibition studies using DHAS as substrate, E₁S and P₅S were competitive inhibitors with inhibition constants (K_i) of 4.8 ± 1.3 and 0.7 ± 0.1 Mmol/L, respectively. Using P₅S as substrate, E₁S and DHAS also were competitive inhibitors with K_i values of 8.2 ± 2.1 and 9.6 ± 1.2 µmol/L, respectively. For both substrates, the pattern of inhibition by C₂₇S was complex. Preliminary experiments to distinguish, on the basis of differing physical-chemical properties, separate enzymes for different substrates were inconclusive.

We conclude that human chorion and decidua can hydrolyze several steroid sulfoconjugates and this activity may regulate local estrogen and progesterone synthesis. There are significant interactions among steroid sulfoconjugates in regulating this activity. These activities may be important components of a paracrine system that determines myometrial contractility and the timing of parturition.

Received October 16, 1989.

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