MECHANISM OF THE STIMULATORY EFFECT OF CLOMID® ON AROMATIZATION OF STEROIDS BY HUMAN PLACENTA IN VITRO

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Abstract
The in vitro rate of conversion of testosterone to oestrone and oes-tradiol by a preparation of human placental microsomes was increased by the addition of Clomid*. The effect was a function of the amount of Clomid added, the maximum observed being 1.6 times that in control vessels containing no Clomid. Of the cis-trans isomers of Clomid, the form designated as isomer A was three times as effective as isomer B in accelerating aromatization. The minimal effective concentration of the mixed isomers in the incubation mixture was 0.2 mM. The mechanism of this effect was shown to be a noncompetitive inhibition of the NADPH: Cytochrome c oxidoreductase system, thereby interfering with a major route of NADPH disposition in the microsomes and increasing the availability of NADPH for the aromatization reaction. The findings suggest a possible mechanism for a direct stimulatory influence of Clomid upon the ovarian biosynthesis of oestrogens in vivo, although the concentration of the drug required for significant acceleration of placental aromatization in vitro was considerably greater than its probable concentration in ovarian tissue following Clomid administration to women.

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