The effect of reproductive hormones on cortisol levels during pregnancy
At the onset of gestation, progesterone and oestrogen are secreted by the corpus luteum in moderate amounts. The placenta then takes over progesterone and oestrogen synthesis for the rest of the pregnancy. Progesterone secretion can increase up to 40-fold by the third trimester during a normal pregnancy and oestrogens levels increase up to 30-fold by full term. Both progesterone and oestrogen receptors are expressed in the pancreatic islets of Langerhans and regulate β-cell viability and function [195]. Progesterone has a faster association for CBG than cortisol and higher levels of progesterone during pregnancy may displace cortisol from CBG, increasing plasma cortisol [196]. Progesterone can also be converted to cortisol via 17-α-hydroxylase and 21-hydroxylase in the adrenal glands [197].
Increasing placental oestrogen stimulates the production of CBG by the liver, therefore altering the pharmacokinetics of cortisol [181]. Fetal ACTH secretion is increased as oestrogen is secreted in increasing amounts by the placenta in late gestation [198]. Oestrogen escalates and androgens reduce basal and stimulated ACTH secretion [199]. The levels of circulating ACTH and cortisol concentrations change during the normal menstrual cycle in women, where the highest concentrations of these hormones are measured in tandem with the highest circulating levels of oestrogen [200]. Therefore, oestrogen levels rise in women either during the menstrual cycle or pregnancy, altering CBG production, upregulating 11β-HSD1 levels or directly stimulating the pituitary gland, causing an overall rise in plasma cortisol.