Synthesis and function of hypothalamic neuroprogesterone in reproduction

The physiology and regulation of steroid synthesis in the brain have emerged as important for understanding brain function. Neurosteroids, those steroids synthesized de novo in nervous tissue, have been associated with numerous central nervous system functions, including myelination, mental retardation, and epilepsy. Central regulation of reproduction was thought to depend on steroids of peripheral origin. Only recently has the role of neurosteroids in reproduction been appreciated. This minireview describes our work trying to understand how circulating estradiol modulates the synthesis of neuroprogesterone. The synthesis of neuroprogesterone occurs primarily in astrocytes, and requires the interaction of membrane-associated estrogen receptor with metabotropic glutamate receptor and the release of intracellular calcium stores. The newly synthesized neuroprogesterone acts on estradiol-induced progesterone receptors in nearby neurons to initiate the LH surge.