Glucocorticoid involvement in reproductive biology

Oestrogen and progesterone play essential roles in the release of mature oocytes, the priming and cycling of the uterine lining, and the maintenance of mammalian pregnancy. Progesterone is synthesizedde novoat the embryo implantation site in the mouse, during decidualization of the endometrium. During early stages of pregnancy, the locally produced progesterone is thought to act as an immunosuppressant, preventing rejection of the fetal allograft at the fetal-maternal interface. However, both uterine natural killer cells and dendritic cells express glucocorticoid receptor rather than progesterone receptor. The importance of glucocorticoids in early pregnancy is inferred from the presence of steroid receptors and the 11β-hydroxysteroid dehydrogenase enzymes, which modulate corticosterone action in the decidua, the trophoblast, the placenta, and the fetus. 11β-hydroxylase is the last enzyme in the metabolism of cholesterol to corticosterone and, in a mouse model of 11β-hydroxylase deficiency, complications of reproduction suggested its requirement for normal ovulation and uterine cell turnover. We present evidence that, in this model, folliculogenesis occurs normally but ovulation is inhibited, and abnormal uterine cell turnover ultimately leads to adenomyosis. Ovaries respond to a superovulation protocol by releasing oocytes and forming corpora lutea, and homozygous null blastocysts are capable of implantation, but the pregnancy is not maintained. We show that glucocorticoid is produced locally at the implantation site in control animals, revealing wide involvement of glucocorticoids in reproductive biology.