Pregnancy maintenance and the regulation of placental progesterone biosynthesis in the baboon

Abstract

Progesterone (P4), a major steroid hormone produced by the ovarian corpus luteum (CL) and the placental syncytiotrophoblast, is considered essential for the successful maintenance of mammalian pregnancy. It has been demonstrated in our laboratory and in the laboratories of others, that the baboon (Papio anubis/cynocephalus) is an excellent model for study of the endocrinology of human pregnancy. Results from both in-vivo and in-vitro experiments indicate that oestrogen stimulates placental P4 production by regulation of cholesterol side chain cleavage cytochrome P-450 and through the uptake of cholesterol via the low density lipoprotein (LDL) pathway. Thus, LDL uptake by the baboon placental syncytiotrophoblast increases in response to maternal oestrogen concentration, which increases with advancing gestation. Conversely, both placental LDL uptake and maternal peripheral P4 concentration decline significantly at mid- to late gestation as a result of oestrogen deprivation by either anti-oestrogen administration or the removal of fetal androgen oestrogen precursors through fetectomy. Utilizing these methods, it has been possible to decrease cellular uptake of LDL-cholesterol and, hence, maternal peripheral P4 to only a small fraction of their normal concentrations, although P4 is still detected in the maternal periphery in concentrations adequate for preservation of the conceptus. We postulate that such levels of maternal P4 are derived from cholesterol precursor provided by sources alternate to the classical LDL-receptor pathway and are produced throughout gestation by the placental syncytiotrophoblast and perhaps during late pregnancy by a resurgent CL. We further postulate that regulation of these ancillary sources of cholesterol substrate is subject to LDL-cholesterol availability in the maternal peripheral circulation and to possible ontogenetic changes in both primary and secondary cholesterol-yielding mechanisms, which may be divergently regulated in the steroidogenically active syncytiotrophoblast from those in proliferative non-endocrine placental constituents.