Nontranscriptional effects of estradiol in neuropeptide neurons

Although the negative feedback of estrogen on the hypothalamus and pituitary has been recognized for more than 60 years, the cellular mechanism by which estrogen inhibits gonadotropin-releasing hormone and gonadotropin secretion has been elusive. This review describes recent progress in our understanding of the rapid or nongenomic effects of estrogen. In particular, it has been recently found that estrogen rapidly activates a protein kinase pathway to alter synaptic transmission in hypothalamic neuropeptide neurons that directly inhibit gonadotropin-releasing hormone neurons. In addition to these rapid effects, the newly discovered biochemical pathways have the ability to alter transcription themselves, as well as to modulate the genomic effects of the classic estrogen receptor. Work is currently under way to further define the receptor and the biochemical mechanisms that mediate these rapid actions of estrogen.