Cortisol levels during pregnancy
Circulating and bound levels of cortisol both increase as gestation proceeds to levels that are similar to those detected in Cushing’s syndrome, with plasma levels of cortisol reaching 2- to 3-fold higher than observed in non-pregnant women [181-184]. The rise in cortisol levels begins in week 11 and continues to rise and peak between the first and second trimester to a maintenance level during the third trimester [185]. The salivary cortisol in pregnant women is twice as high as in non-pregnant women in the third trimester [181,186], and the circadian rhythm of cortisol is partly blunted [181,186]. Plasma ACTH levels rise throughout pregnancy reaching a peak during labour and delivery, with placental ACTH production being a significant contributor to hypercortisolism in pregnancy [181]. CRH is synthesized in the human syncytiotrophoblast and released into both the maternal and fetal blood in significant quantities [187,188]. In contrast to the hypothalamic CRH system, the placental production of CRH is stimulated by glucocorticoids [189], providing a positive feedback system, which is a unique characteristic of placental CRH and indicates a role for CRH in late stages of gestation [190]. Exposure to elevated cortisol levels early in the pregnancy may accelerate placental synthesis and the release of corticotrophic releasing hormone to precipitate early delivery [191]. Placental hypersecretion of CRH mid gestation has been proposed as a predictive marker of subsequent preterm delivery [192]. It has been postulated that towards the end of the gestation period CRH stimulates cortisol production in the foetal adrenal glands [193,194].