Molecular biology in reproductive endocrinology

Through the study of naturally occurring mutations in humans, the creation of mutations by site-directed mutagenesis, and the production of transgenic knockout mice, further understanding of molecular reproductive endocrinology had been achieved. Mutations in the aromatase gene in females have confirmed that its deficiency results in a previously unrecognized form of sexual ambiguity with a 46,XX karyotype, and delayed puberty with multicystic ovaries. It has long been known that estrogen is necessary for skeletal growth and epiphyseal closure in the female, but aromatase and estrogen receptor gene mutations in men have demonstrated, for the first time, that estrogen is important for epiphyseal closure in the male. Mutations in the steroidogenic acute regulatory protein have been recently described that demonstrate the cause for lipoid congenital adrenal hyperplasia, a disorder characterized by the complete lack of steroid production. New gene mutations in gonadotropin β-subunits, pituitary hormones, G protein coupled receptors, G proteins, steroid enzymes and their receptors have also been characterized recently. Site-directed mutagenesis experiments and transgenic knockout mice have been increasingly used to study the effects of normal endocrine function. Normal functions of steroid receptor genes (steroidogenic factor- 1, estrogen receptor, progesterone receptor) the glycoprotein α-subunit, luteinizing hormone β, and proto-oncogenes such as RET have been better characterized by creating knockout models. Molecular biology techniques permit these types of studies which may be difficult, if not impossible, to perform otherwise in physiologic settings.