Placental steroids in cattle: Hormones, placental growth factors or by-products of trophoblast giant cell differentiation?

The bovine placenta produces large amounts of steroids, mainly estrone (E1) and progesterone (P-4). Specific features of bovine placental steroidogenesis are I) the expression of all enzymes needed for the production of estrogens from cholesterol in the trophoblast 2) an only marginal and temporal contribution to peripheral maternal P4 levels restricted to a period between approx. days 150-240 of gestation 3) the predominance of sulfoconjugated over free El and 4) a complementary setting of steroidogenic enzymes in the two morphologically discriminable trophoblast cell types, the uninucleated trophoblast cells (UTC) and the trophoblast giant cells (TGC). In cattle so far no definite information is available on the specific biological roles of placental estrogens and P4. However, the detection of estrogen receptors and progesterone receptors in the placentomes Suggests a role primarily as local regulators of caruncular growth, differentiation and functions. Inconsistent with a function as a caruncular growth factor is the strong evidence that in cattle placental estrogens enter the maternal compartment almost completely as estrone Sulfate (EIS), which is not active at classical nuclear receptors. Oil the other hand, E IS may be converted locally to free active estrogens via the action of steroid sulfatase (StS), which has been detected in specific parts of the bovine carancular epithelium. Alternatively or in addition, StS expression in the caruncular epithelium may serve the utilization of sulfated neutral steroid precursors (e.g. pregrienolone sulfate or cholesterol sulfate) supplied with maternal blood, thus providing free substrates for further metabolization in the adjacent trophoblast. The down-regulation of P450scc and P450c17 and the Up-regulation of 3B-HSD and aromatase during the differentiation of TGC from UTC in parallel with the up-regulation of ERE and estrogen sulfotransferase in maturing TGC suggests a function of placental estrogens primarily as auto-or intracrine regulators during this process and assigns to conjugated placental estrogens a role as inactivated by-products of TGC differentiation intended for excretion. Collectively, despite some evidence from recent studies for putative roles of placental steroids in cattle their exact functions in the bovine species remain still undefined.German Research Foundation (DFG)The Ewald and Hilde Berge Foundatio