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Endocrinology, doi:10.1210/en.2008-0927
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Endocrinology Vol. 150, No. 6 2783-2790
Copyright © 2009 by The Endocrine Society

Estrogens Regulate Posttranslational Modification of Neural Cell Adhesion Molecule during the Estrogen-Induced Gonadotropin Surge

Orkun Tan, Ahmed Fadiel, Aimee Chang, Necdet Demir, Rachel Jeffrey, Tamas Horvath, Luis-Miguel Garcia-Segura and Frederick Naftolin

Department of Obstetrics and Gynecology (O.T., A.F., F.N.), New York University School of Medicine, New York, New York 10016; Department of Obstetrics and Gynecology (A.C., N.D., R.J., T.H.), Yale University School of Medicine, New Haven, Connecticut 06511; and Instituto Cajal (L.-M.G.-S.), Consejo Superior de Investigaciones Cientificas, Madrid E-28002, Spain

Address all correspondence and requests for reprints to: Frederick Naftolin, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York 10016. E-mail: frederick.naftolin{at}nyumc.org.

Estrogen-induced synaptic plasticity (EISP) in the periventricular area (PVA) of the hypothalamus is necessary for the preovulatory gonadotropin surge. Because in situ enzymatic desialization of hypothalamic polysialylated (PSA) neural cell adhesion molecule (NCAM) blocked EISP, we examined the presence and amount of NCAM isotopes, PSA-NCAM, and sialylation enzymes in microdissected mouse hypothalamus tissues from proestrous afternoon [peak of estrogens and nadir of arcuate nucleus (AN) synapses] and metestrous morning (nadir of estrogens and highest AN synapses). Immunohistochemistry confirmed immunoreactive (ir) PSA-NCAM staining in the perineural spaces of the PVA. The extent of staining was cycle dependent, with more dense and complete profiles of individual neurons limned by the ir-PSA-NCAM staining on proestrus and less on metestrus. Western blots showed that high levels of ir-PSA-NCAM on proestrus are accompanied by diminished ir-NCAM-140 and -180 but not ir-NCAM-120 and the reverse on metestrus (P < 0.05). To evaluate the increase of sialylated NCAM at the expense of desialylated protein, expression of the responsible polysialyltransferase enzymes polysialyltransferase (ST8Sia IV) and sialyltransferase (ST8Sia II) mRNA levels were measured using RT-PCR. Both polysialyltransferase and sialyltransferase mRNA are more abundant on proestrus than metestrus (P < 0.05), indicating that these enzymes are regulated by estrogens. These results support estrogen-regulated formation and extrusion of hydrophilic PSA-NCAM into perineural spaces in the PVA as part of the mechanism of EISP.







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