Placental Steroid Hormone Biosynthesis in Primate Pregnancy*

Abstract

Substantial advances in our understanding of placental function have resulted from recent establishment of in vitro approaches, such as cell culture, and application of molecular methods to study placental steroidogenesis. Insight into the processes of placental cell differentiation and hormonal function has been gained from culture of relatively pure preparations of cytotrophoblast. Various factors, e.g. cAMP and peptide growth factors, have been shown to have striking effects on progesterone and estrogen formation by placental tissue under in vitro conditions. Using advanced molecular approaches, the genes governing specific enzymes critical to placental steroidogenesis have been identified. Regulation of the mRNAs encoding specific enzyme peptides and thus expression of the genes by factors, such as cAMP, have been elucidated by Northern analysis and other techniques. It is critical that these contemporary approaches continue to be implemented aggressively to further elucidate placental function. However, it is clear from a survey of the literature, particularly of the past decade, that the vast majority of investigation in the area has been conducted in vitro. It is essential to determine whether the factors that have been observed to regulate placental endocrine function in vitro are operable in vivo. It is only with in vivo study that the dynamics of steroidogenesis and the complex functional relationships between placenta, fetus, and mother will be uncovered and understood. It is increasingly evident that the regulation of placental steroidogenesis involves autocrine and/or paracrine mechanisms, similar to those integral to hormone biosynthesis within other reproductive organs, e.g. ovary and testis. For example, as discussed above, estrogen regulates LDL uptake and P-450scc, and thus apparently is involved in generating substrate for progesterone production within the placenta. Conversely, progesterone has effects on 17 beta-hydroxysteroid oxidoreductase and thus the metabolism of estradiol, while androgens exert marked inhibitory effects on placental progesterone formation, at least in vitro. Not surprisingly, the regulation of placental progesterone and estrogen formation also is multifactorial. Thus, aromatase activity is stimulated synergistically by cAMP and phorbol esters, an effect that is suppressed by peptide growth factors. Therefore, the autocrine/paracrine and multifactorial regulation of hormone biosynthesis that has been relatively well documented in other tissues should be recognized as important in the primate placenta. Finally, the basic mechanisms underlying regulation of steroidogenesis within the fetoplacental unit during primate pregnancy appear similar, in important ways, to those of widely used laboratory animals, such as the rat and rabbit.(ABSTRACT TRUNCATED AT 400 WORDS)

Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

“…In isolated muscle, increased lactate release and reduced pyruvate oxidation were observed after exposure to 1 μmol/l progesterone, a concentration that is reached in plasma of pregnant women and rats [3,4]. Hence, a surplus of lactate from skeletal muscle could contribute to elevated plasma concentrations as well as to increases in hepatic lactate uptake and in gluconeogenesis from lactate of pregnant rats [31,32].…”

“…While several peptide and steroid hormones could make a contribution, a strong line of evidence points at a predominant role of circulating progesterone, which during the course of pregnancy increases in tight association with the reduction in insulin-stimulated glucose disposal [3,4]. The presumptive function of progesterone as a physiological modulator of glucose homeostasis is supported by parallel fluctuations of endogenous plasma progesterone concentrations and insulin sensitivity during the human menstrual cycle [5,6], as well as by a correlation between the plasma concentrations of progesterone and glucose in female mice studied randomly during their cycle [7].…”

Deletion of the Mouse P450c17 Gene Causes Early Embryonic Lethality

“…Estrogen and progesterone are necessary to establish and sustain pregnancy in mammals (1,31,42). Steroid synthesis in pregnancy involves the maternal ovarian corpus luteum, the placenta, and, in some species, the fetus as well.…”

Differential Expression of Placental Villous Angiopoietin-1 and -2 During Early, Mid and Late Baboon Pregnancy

“…We have recently shown that estrogen, the levels of which increase with advancing human and baboon pregnancy [25], stimulated placental trophoblast VEGF expression in the baboon [11,12]. In contrast, estrogen decreased the expression of Ang-1 in the lung, kidney and heart [26].…”