Glucocorticoid Regulation of Human and Ovine Parturition: The Relationship Between Fetal Hypothalamic-Pituitary-Adrenal Axis Activation and Intrauterine Prostaglandin Production

Abstract

Birth in many animal species and in humans is associated with activation of hypothalamic-pituitary-adrenal function in the fetus and the increased influence of glucocorticoids on trophoblast cells of the placenta and fetal membranes. We suggest that in ovine pregnancy glucocorticoids directly increase fetal placental prostaglandin production, and indirectly increase prostaglandin production by maternal uterine tissues through the stimulation of placental estradiol synthesis. The events of ovine parturition are compared with those of human parturition. In the latter, we suggest similar direct effects of glucocorticoids on prostaglandin synthesis and metabolism in fetal membranes and similar indirect effects mediated by glucocorticoid-stimulated increases in intrauterine corticotropin-releasing hormone expression.

Reciprocal expression of 17α-hydroxylase-C17,20-lyase and aromatase cytochrome P450 during bovine trophoblast differentiation: a two-cell system drives placental oestrogen synthesis

“…As for P450c17, a prepartal up-regulation of expression starting from areas close to the chorionic plate towards the tips of CV located adjacent to the caruncular stalk has also been observed for the glucocorticoid receptor in TGCs and caruncular epithelial Steroidogenic enzymes in bovine placentomes 673 cells (Boos et al 2000), cyclo-oxygenase-II (COX-II) in UTCs (Schuler et al 2006) and steroid sulphatase in caruncular epithelial cells (Greven et al 2005), possibly indicating a similar transcriptional control. In the sheep, a pre-and intrapartal increase of placental P450c17 has been shown to promote the increased production of oestrone, a crucial step in the initiation of parturition in this species (Mason et al 1989, Gyomorey et al 2000, Whittle et al 2001. A similar process previously confirmed for the cow at the level of enzyme activity (Schuler et al 1994) has now been characterised at a cellular level in this study.…”

“…A similar process previously confirmed for the cow at the level of enzyme activity (Schuler et al 1994) has now been characterised at a cellular level in this study. In the sheep, the up-regulation of COX-II in UTCs and a subsequent rise in placental prostaglandin E 2 levels have been suggested to stimulate the pre-and intrapartal rise of P450c17 expression (Whittle et al 2000(Whittle et al , 2001. A similar prepartal rise in COX-II expression of UTCs has recently also been confirmed for the cow (Schuler et al 2006).…”

Investigations into the mechanisms controlling parturition in cattle

“…So far the sheep has served as an important animal model and detailed information on the regulatory mechanisms leading to birth is available for this species (for review see Whittle et al (2001)); in the ovine fetus at the end of gestation, maturation of the hypothalamo-pituitary-adrenal (HPA) axis leads to a substantial increase in fetal cortisol, triggering in uninucleated trophoblast cells (UTC) an upregulation of cyclooxygenase 2 (COX2) and of the steroidogenic key enzyme 17a-hydroxlyase-C17, 20-lyase (CYP17). The latter channels placental metabolism of pregnenolone into the D5-pathway resulting in a dramatic decrease in progesterone and an enhanced synthesis of estrogens.…”

Avaliação hormonal sérica e estereológica da membrana corioalantóide a termo de éguas: influência no desenvolvimento e nos parâmetros clínicos e metabólicos do potro

“…Concomitante ao aumento das concentrações de glicocorticoides fetal ocorre um aumento progressivo na síntese de prostaglandinas (PGs), em particular a prostaglandina E 2 (PGE 2 ), no plasma, líquido amniótico e tecidos uterinos de mulheres e ovelhas (WHITTLE et al, 2001). Esse incremento de PGE 2 é seguido de um aumento na produção de prostaglandina F 2α (PGF 2α )e inicio do parto (CHALLIS; LYE; GIBB; 1997).…”

“…As concentrações in útero de PGE 2 aumentam paralelamente com as concentrações de cortisol plasmático fetal CHALLIS et al, 2000;WHITTLE et al, 2001). Além disso, foi demonstrado que a PGE 2 aumentou a expressão de P450C 17 nas células corticais da adrenal de bovinos, sugerindo que esta PG pode estar diretamente envolvida com a síntese de cortisol (RAINEY et al, 1991).…”