INVESTIGATIONS ON THE USE OF C-21-STEROIDS AS PRECURSORS FOR PLACENTAL ESTROGEN SYNTHESIS IN THE COW

Cotyledonary homogenates from 220 and 270 day pregnant and term cows w ere incubated (NADPH-and NAD(+)-regenerating system) with H-3-pregneno lone and H-3-progesterone, respectively. Identification of metabolites was based on separation on HPLC and the respective retention times. O n days 220/270 the major metabolite formed after incubation with H-3-p regnenolone was progesterone, followed by 17 alpha-hydroxyprogesterone and dehydroepiandrosterone/17 alpha-hydroxypregnenolone; the formatio n of estrone was low (up to 6%), while it was the major metabolite aft er incubation of pregnenolone with term placenta. At all stages of pre gnancy investigated, the only metabolite found after incubation with H -3-progesterone was 17 alpha-hydroxyprogesterone. These data provide e vidence that 17 alpha-hydroxyprogesterone is the endpoint of steroid b iosynthesis in the bovine placenta along the Delta 4-route and that oe strogen synthesis follows the Delta 5-pathway. Based on the high avcti vity of 3 a-hydroxysteroiddehydrogenase/Delta(5/4)-isomerase also foun d on days 220/270, the key enzyme allowing for placental oestrogen syn thesis in the cow seems to be cytochrome P450c17 alpha. Thus the situa tion in the cow is similar to that in the sheep and the increased turn over of pregnenolone into estrone may explain the decrease of placenta l progesterone production in the cow towards the end of gestation.