Sheperd, Leonie Anne; (1997) Investigations into the control of placental steroid production. Masters thesis (M.Phil), UCL (University College London).

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Abstract

During normal human pregnancy there is a gradual rise in plasma progesterone and oestrogen levels with a steep rise in oestriol concentrations a few weeks before term. Taken in conjunction with the known effects of progesterone and oestrogens on the myometrium these changes suggest that the regulation of the production of these steroids by the placenta may be important in maintaining uterine quiescence and in initiating labour, respectively. The aim of this study was to assess the effect of corticotrophin releasing hormone, adrenocorticotrophic hormone and the insulin like growth factors I and II, on the placental production of progesterone and oestrogens. Placental minces and isolated cytotrophoblast cells were incubated with various steroid precursors at 37[degrees]C with/without these substances. The production of progesterone, oestrone, oestradiol and oestriol was measured by radioimmunoassay. The effects of these substances on the enzyme systems, cholesterol side chain cleavage, [beta]-hydroxysteroid dehydrogenase, aromatase and 17[beta]-hydroxysteroid dehydrogenase were studied. There was very little cholesterol side chain cleavage activity in isolated cells when 25-hydroxycholesterol was used as a precursor but [beta]-hydroxysteroid dehydrogenase, aromatase and 17[beta]-hydroxysteroid dehydrogenase were active when pregnenolone, androstenedione and 16[alpha]-hydroxyandrostenedione respectively were used as precursors. Androstenedione inhibited the production of oestriol by isolated cells when 16[alpha]-hydroxyandrostenedione was used as a precursor. The addition of NADPH to placental tissue explants resulted in significantly raised progesterone and oestradiol production but not oestrone or oestriol. The results suggest that the energy supply to the enzyme systems responsible for the production of progesterone and oestradiol is rate limiting for the overall reaction. There was no consistent significant effect of corticotrophin releasing hormone, adrenocorticotrophic hormone or the insulin like growth factors on progesterone, or oestrogen production in either tissue explants or isolated cytotrophoblast cells under the experimental conditions used in this study.

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