Editorial [Hot topic: Membrane Estrogen Receptors (Guest Editor: Paul J. Davis)]

Nongenomic actions of nonpeptide hormones initiated at the cell surface have been described for estrogen [1, 2], dihydrotestosterone [3], vitamin D [4, 5] and thyroid hormone [6, 7]. Reviews of some of these actions have recently appeared in Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry [8, 9]. Quite specific membrane protein receptors have been defined for DHT [3], vitamin D [4] and iodothyronines [6]. The term, ‘receptor,’ is justified here because discrete downstream consequences of ligand-protein interactions are reported. The nature of the receptor(s) in extranuclear actions of estrogen has been controversial. Classical nuclear estrogen receptors (ERs) residing in cytoplasm or inserted in the plasma membrane have been described, but evidence also exists for estrogen-binding by a G protein-like receptor (GPR) or an STX-binding protein. Papers by Drs. Marino and Galluzzo and by Drs. Micevych and Mermelstein in this issue of the journal critically review the current state of our knowledge of these receptors. Marino and Galluzzo discuss the dynamic model of ERs shuttling among cellular compartments-plasma membrane-cytoplasm-nucleus-and how different cellular effects might be achieved with this model. Such models teach that functional distinctions between nongenomic and genomic actions of the hormone are blurred and less useful than once was conceived to be the case. Micevych and Mermelstein explore rapid-onset actions of estrogen in brain via ERs trafficked to the plasma membrane that activate G proteins to transduce the estrogen signal. Neuronal metabotropic glutamate receptors are involved in the transduction process. Biologic endpoint in these studies is regulation of luteinizing hormone release. The Editor appreciates the efforts of Dr. Boris Cheskis and Ellis Levin in soliciting these papers for the journal.