Defects in Ovarian Steroid Hormone Biosynthesis

The ovary secretes steroid hormones that initiate female sexual development, program the secretion of gonadotropins from the hypothalamic-pituitary axis, and regulate the function of the female reproductive tract. The synthesis of bioactive steroid hormones involves a compartmentalized process within steroidogenic cells in which cholesterol is moved through organelles that modify the sterol backbone and side-chain. Collaborative interactions among steroidogenic cell types, particularly theca and granulosa cells and their luteinized forms, govern the secretion of ovarian androgens, progestins and estrogens. Rare mutations in the genes encoding gonadotropin receptors and steroidogenic enzymes impair steroid hormone production and result in disordered gonadotropin secretion and, consequently, defects in follicular growth and development and ovulation. Polycystic ovary syndrome, a common endocrine disease of women in reproductive age, is associated with abnormal expression of steroidogenic enzymes, also leading to abnormal follicular maturation. This chapter reviews the mutations and genetic variants that alter human ovarian steroidogenesis and the resulting phenotypes.