A sizable problem in our understanding of the control of parturition has been a desire by different investigators to explain the whole mechanism in terms of their current theory. We have been offered explanations in terms of factors such as withdrawal of the systemic progesterone block, the local progesterone block, the volume:progesterone ratio, the progesterone:estrogen ratio, the oxytocin effect, the progesterone:oxytocin effect, the fetal role, and the prostaglandin role. With the coming of age of Endocrinology and the ability to reduce hormone assays to a routine laboratory service, we have at last begun to understand that many, if not all, rather than any one of these individual explanations may be implicated in the control of parturition. We now recognize that in late pregnancy a train of events is initiated that ultimately results in the delivery of the fetus. However, we still do not know exactly how and where that train starts, or exactly how it exerts its ultimate action on the myometrial cell. It is a major objective of this chapter to try to bring together some of the abovementioned theories, and particularly to show that, for example, the role of the fetus in the initiation of parturition and the concept of progesterone withdrawal may be part of the same mechanism. It would be folly to say that at the present time either or both of these concepts explain parturition in all species, but by examining a number of different species we hope to illustrate as many of the discrepancies as similarities.

Endocrine control of parturition

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)

Placental steroid hormone biosynthesis in primate pregnancy.

IT is well known that the free fraction of plasma cortisol is increased in pregnancy1, but it has not been established whether this is a result of maternal pituitary or placental adrenocorticotrophic hormone (ACTH) secretion. Maternal plasma ACTH levels in human pregnancy have been variously reported as elevated2, or depressed3; but there is no information on the relationship between ACTH levels and the stage of gestation. We now report that maternal ACTH levels increase progressively throughout pregnancy, that urinary free cortisol levels are raised and show resistance to suppression by dexamethasone and we present evidence suggesting that ACTH may be produced by the placenta.

Possible placental origin of ACTH in normal human pregnancy.

Elevated free cortisol index in pregnancy: Possible regulatory mechanisms

Pregnant female rhesus monkeys were exposed to a 2-week period of adrenocorticotropic hormone (ACTH) to determine whether it would affect the early neuromotor development of their fetuses in a manner similar to that observed after psychological stressors. During the first month after birth, infants were tested on two occasions with a modification of the Brazelton Newborn Behavioral Assessment Scale. Infants derived from ACTH-treated pregnancies showed early impairments in motor coordination and muscle tonicity and shorter attention spans as compared to controls. In addition, on a temperament rating scale, infants from the ACTH condition were more irritable and difficult to console. These findings indicate that a delimited period of endocrine activation during pregnancy can have an adverse effect on infant neurobehavioral development, like that of prenatal stress. © 1992 Wiley & sons. Inc.

Anita S. Gold

Papers

On the regulation of estrogen production by cortisol and ACTH in human pregnancy at term. Memorial Foundation award thesis.