[Estrogen, progesterone--biosynthesis, receptor and action]

Ovarian sex steroid hormones, estrogen and progesterone, have crucial effects on female reproductive functions such as the development and maturation of reproductive organs and the appearance of normal menstrual cycles. The precursor of steroid hormones is a cholesterol that is synthesized de novo from acetate or that is taken in as LDL-cholesterol via LDL-receptor. Members of cytochrome P450 superfamily and hydroxysteroid dehydrogenase (HSD) involved in the biosynthesis of the steroid hormones. In the corpus luteum, P450scc and 3 beta-HSD catalyze the pathway from cholesterol to progesterone and in the granulosa cells, P450arom (aromatase) and two HSDs catalyze the biosynthesis of estrogen from C19 steroid synthesized in the theca cells having P450(17) alpha. In the target cell, steroid binds to and activates its receptor located primarily in the nucleus. Binding of ligand results in dimerization of the receptor due to its conformational change. The steroid-receptor complex binds to specific hormone responsive element of the target gene at the site of DNA binding region and then activates transcription of the gene. Main action of estrogen is to stimulate the proliferation and development of cells due to enhancement of the synthesis of specific DNAs and proteins in the female reproductive organs. Progesterone regulates the action of estrogen through the decrease of estrogen receptor and down regulation of its own receptor.