Steroidogenesis and the initiation of parturition

One of the most fundamental axioms of mammalian reproduction is that pregnancy requires the support of progesterone without which it cannot be established or maintained. Though this basic physiological tenet was accepted long ago, major gaps in our understanding of the physiology of both pregnancy and parturition remain which hamper our ability to solve clinically and agriculturally significant problems such as low fertility, fetal growth restriction, preterm birth and poor neonatal outcomes. The historical reliance of our understanding of both pregnancy and parturition on this single hormone, and how it has been measured in the vast majority of studies, may represent a tangible weakness and impediment to progress. Other weaknesses include a desire to fit all species into a unified paradigm, and a reluctance to accept that physiological processes regulated by progesterone or other progestins in different tissues might vary in reliance on classic (nuclear receptor) versus other, non-classical mechanisms of action. The relative importance of these distinct response pathways in certain cells or tissues also may differ across species, as does so much of basic reproductive physiology. It is well known that certain species are reliant on luteal function throughout gestation, whereas the placenta subsumes endocrine support in others (Geisert & Conley 1998), yet progesterone alone is still believed to be the single common element. As radical as it might seem, however, progesterone may not be the single common hormone of pregnancy in mammals.