Maria Serón-Ferré

Regulation and Function of the Primate Fetal Adrenal Gland and Gonad

Publisher Summary Although the steroid-producing glands of the fetus, the adrenal gland and gonads, arise from proximate embryologic sites, their functions are markedly disparate. This chapter discusses the regulation and functions of the primate fetal adrenal gland and gonad. Glucocorticoids secreted by the fetal adrenal gland play an important role in affecting homeostatic adjustments necessary for extrauterine life. These secretions affect the maturation of a variety of enzyme systems, including the liver, the pancreas, and the gastrointestinal tract. In contrast, the gonads subserve different functions. In the male, the testis elaborates both testosterone—an essential stimulator of Wolffian ductal development—and a Mullerian inhibiting factor that prevents the development of the Mullerian ductal system. The chapter focuses on the works concerning the regulation and function of the human and subhuman primate fetal adrenal gland and gonads. There is functional specialization of the fetal and definitive zones of the human fetal adrenal gland as demonstrated in superfusion studies.

Regulation of the primate fetal adrenal gland and testis in vitro and in vivo.

Abstract In vitro experiments with the separated fetal zone (FZ) and definitive zone (DZ) of the human fetal adrenal (10–20 weeks) demonstrated ACTH stimulation of cortisol and binding in the DZ. Dehydroepiandrosterone sulfate (DHAS), produced primarily in the FZ, was stimulated inconsistently by ACTH, but consistently by hCG. Thus, the DZ appears regulated by ACTH, and the FZ principally by hCG in the first half of gestation. To assess adrenal regulation in the primate during the second half of gestation, under more physiologic circumstances, studies were carried out in a chronic fetal rhesus monkey preparation in utero in which fetuses (130–145 d gestation) were catheterized, replaced in the uterus, and the pregnancy allowed to continue up to 14 days. Dexamethasone administered to the fetus suppressed DHAS, cortisol and ACTH. Seven fetuses were challenged with ACTH. An increase in cortisol production was only observed in two; no significant stimulation was seen in the others. The challenge with ACTH was given to two infant monkeys on the first day of life. Cortisol levels increased 10-fold after ACTH stimulation. The data suggest some intrauterine factor which blocks the response to ACTH. In studies of fetal monkey testicular regulation, in vitro and in vivo, specific hCG binding was demonstrated in testicular homogenates and hCG stimulated testosterone (T) production in testicular minces. In utero intra-arterial administration of hCG to fetuses resulted in a 4-fold increase in fetal serum T. Other fetuses were challenged with bolus infusions of 10 and 50 μg gonadotropin releasing hormone (GnRH). Only the higher dose resulted in fetal T stimulation. In newborn monkeys, the lower 10 μg dose of GnRH also caused an increase in serum T. Thus, the pituitary-adrenal and pituitary-gonadal axes appear functional in the third trimester in this species, and target gland sensitivity appears to increase after birth.

SOME NEW THOUGHTS ON THE FETOPLACENTAL UNIT AND PARTURITION IN PRIMATES

Publisher Summary A striking aspect of human pregnancy is the variability of blood estrogen and progesterone levels that are consistent with a normal outcome. If, indeed, characteristic changes in estrogen and progesterone or possibly in the ratio of these two hormones are prerequisites to parturition, they have yet to be identified by measurements in maternal blood. The extreme hour-to-hour variability and the broad range of serum levels in normal pregnant women have made it difficult to detect a decline in progesterone or an increase in estrogen before parturition. The source of this variability is unknown. Rapid changes in placental synthesis and secretion related to fetal adrenal activity, alterations in uterine blood flow, or alterations in steroid binding to serum proteins may be involved. The failure to find clear-cut patterns in maternal blood does not rule out the possibility that important intrauterine hormonal changes have profound effects on the activation of myometrial contractions or cervical softening. This chapter presents a model for parturition in primates based upon an increased fetal adrenal secretion of dehydroepiandrosterone and its utilization for estrogen synthesis within the fetal membranes.

The primate fetal pituitary-adrenal axis in the perinatal period.

Abstract Fetal adrenal corticosteroids have been implicated in fetal lung development, enzyme induction, and the timing of parturition. Therefore, adrenal function and regulation in fetal and newborn rhesus monkeys were studied in the perinatal period. Plasma cortisol concentrations were measured by radioimmunoassay in 20 monkey fetuses with long-term catheterization. Concentrations rose significantly (p

Perinatal regulation of cortisol in the primate

These studies were designed to assess regulation of steroidogenic function of the human and rhesus monkey fetal adrenal gland. Studies were performed in vitro using superfusion and, in the monkey, in vivo, using fetal monkeys bearing catheters chronically implanted in utero. In vitro, there is functional specialization of the fetal and definitive zones of the human and monkey fetal adrenal glands. The definitive zone produces cortisol stimulable by ACTH and the fetal zone produces principally dehydroepiandrosterone sulfate which also can be stimulated by ACTH. In vivo, an increase in cortisol was seen in the fetal circulation toward the end of gestation. Administration of dexamethasone caused a prompt reduction in fetal cortisol and ACTH, indicating integrity of the fetal pituitary-adrenal axis. When fetal monkeys were challenged with 0.5 i.u. of ACTH only three of the nine studied had a cortisol response. In contrast, newborns delivered by hysterotomy and those delivered vaginally following labor all responded to ACTH stimulation. The responses of the newborns delivered vaginally after labor were greater than in the group delivered by hysterotomy prior to labor. The fetal metabolic clearance rate (MCR), production rate (PR), secretion rate (SR) and placental transfer of cortisol were determined in utero. The MCR of cortisol in the fetus was markedly greater than in the newborn which, in turn, was greater than in the adult. The PR of cortisol was higher in the fetus than in the mother when expressed on the basis of body weight. The difference between PR and SR in the fetus is due to transplacental passage of cortisol from the mother. Expressed on the basis of body weight, SRs in fetus and mother were not significantly different. There is an increase in fetal cortisol SR toward the end of pregnancy and immediately prior to or during labor which may play a role in parturition.