Membrane Estrogen Receptors in Human Spermatozoa: An Example of a Non-Classic Steroid Receptor Located in the Membrane
Estrogens have been described to act through binding to their specific receptors (ERα and ERβ) localized at the cytosolic and nuclear level. Ligand binding results in estrogen receptor (ER) release from the bound heat shock proteins and induces ER dimerization. ER dimers exist in three different isoforms: the homdimers α/α and β/β and the heterodimers α/β. Upon dimerization, the estradiol (E2)-ER complex translocates to the cellular nucleus were it interacts through DNA binding domain with specific DNA sequences regulating transcription of target genes (Fig.l). Recently, in contrast to these well known genomic effects at the transcriptional level mediated by the classical nuclear receptors ERα and ERβ. rapid effects of estrogens arising between seconds to few minutes from stimulation, have been described in different cellular models [for review see 1, 2, 3]. Indeed, both 17βE2 and its cell-impermeant conjugate E2-BSA induce activation of intracellular second messengers such as calcium, nitric oxide formation, and activation of kinases, in neuronal, vascular and bone systems [1, 2, 3] (Fig.l). Such rapid nongenomic effects are initiated at the plasma membrane, but the nature and characteristics of the receptor(s) involved is still a matter of debate .
KeywordsAlbumin Estrogen Tyrosine Progesterone Androgen
Coleman KM, Smith CL.
Intracellular signaling pathways: nongenomic actions of estrogens and ligand-independent activation of estrogen receptors. Front Biosci. 2001,6:D1379–91PubMedCrossRefGoogle Scholar
Cell localization, physiology, and nongenomic actions of estrogen receptors. J Appl Physiol. 2001, 91:1860–7.PubMedGoogle Scholar
Luconi M, Forti G, Baldi E.
Genomic and nongenomic effects of estrogens: molecular mechanisms of action and clinical implications for male reproduction. J Steroid Biochem Mol Biol. 2002, 80:369–81.PubMedCrossRefGoogle Scholar
Nadal A, Ropero AB, Fuentes E, Soria B.
The plasma membrane estrogen receptor: nuclear or unclear? Trends Pharmacol Sci. 2001, 22:597–9.PubMedCrossRefGoogle Scholar
Razandi M, Pedram A, Greene GL, Levin ER.
Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells. Mol Endocrinol. 1999, 13:307–19.PubMedCrossRefGoogle Scholar
Watson CS, Norfleet AM, Pappas TC, Gametchu B.
Rapid actions of estrogens in GH3/B6 pituitary tumor cells via a plasma membrane version of estrogen receptor-alpha. Steroids. 1999,64:5–13.PubMedCrossRefGoogle Scholar
Chambliss KL, Yuhanna IS, Mineo C, Liu P, German Z, Sherman TS, Mendelsohn ME, Anderson RG, Shaul PW.
Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae. Circ Res. 2000, 87:E44–52.PubMedCrossRefGoogle Scholar
Migliaccio A, Castoria G, Di Domenico M, de Falco A, Bilancio A, Lombardi M, Barone MV, Ametrano D, Zannini MS, Abbondanza C, Auricchio F.
Steroid-induced androgen receptor-E2 receptor beta-Src complex triggers prostate cancer cell proliferation. EMBO J. 2000, 19:5406–17.PubMedCrossRefGoogle Scholar
Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E, Auricchio F.
Tyrosine kinase/p21ras/MAP-kinase pathway activation by E2-receptor complex in MCF-7 cells. EMBO J. 1996, 15:1292–300.PubMedGoogle Scholar
Lagrange AH, Ronnekleiv OK, Kelly MJ.
Modulation of G protein-coupled receptors by an estrogen receptor that activates protein kinase A. Mol Pharmacol. 1997,51:605–12.PubMedGoogle Scholar
Gu Q, Korach KS, Moss RL.
Rapid actions of 17beta-estradiol on kainate-induced currents in hyppocampal neurons lacking intracellular estrogen receptors. Endocrinol. 1999, 140:660–6.CrossRefGoogle Scholar
Benten WP, Stephan C, Lieberherr M, Wunderlich F.
Estradiol signaling via sequestrable surface receptors. Endocrinology. 2001, 142:1669–77.PubMedCrossRefGoogle Scholar
Baldi E, Luconi M, Bonaccorsi L, Maggi M, Francavilla S, Gabriele A, Properzi G, Forti G.
Nongenomic progesterone receptor on human spermatozoa: biochemical aspects and clinical implications. Steroids. 1999, 64:143–8PubMedCrossRefGoogle Scholar
Luconi M, Muratori M, Forti G, Baldi E.
Identification and characterization of a novel functional estrogen receptor on human sperm membrane that interferes with progesterone effects. J Clin Endocrinol Metab. 1999, 84:1670–8.PubMedCrossRefGoogle Scholar
Luconi M, Bonaccorsi L, Forti G, Baldi E.
Effects of estrogenic compounds on human spermatozoa: evidence for interaction with a nongenomic receptor for estrogen on human sperm membrane. Mol Cell Endocrinol. 2001,178:39–45.PubMedCrossRefGoogle Scholar
Espinosa F, Lopez-Gonzalez I, Munoz-Garay C, Felix R, De la Vega-Beltran JL, Kopf GS, Visconti PE, Darszon A.
Dual regulation of the T-type Ca(2+) current by serum albumin and beta-estradiol in mammalian spermatogenic cells. FEBS Lett. 2000,475:251–6.PubMedCrossRefGoogle Scholar
Monje P, Boland R.
Characterization of membrane estrogen binding proteins from rabbit uterus. Mol Cell Endocrinol. 1999, 147:75–84.PubMedCrossRefGoogle Scholar
Hirata S, Shoda T, Kato J, Hoshi K.
The novel isoform of the estrogen receptor-alpha cDNA (ERalpha isoform S cDNA) in the human testis. J Steroid Biochem Mol Biol. 2002, 80:299–305.PubMedCrossRefGoogle Scholar
© Springer Science+Business Media New York 2003