Estrogens regulate posttranslational modification of neural cell adhesion molecule during the estrogen-induced gonadotropin surge.
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.
Tan
Orkun
O
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York 10016, USA.
Fadiel
Ahmed
A
Chang
Aimee
A
Demir
Necdet
N
Jeffrey
Rachel
R
Horvath
Tamas
T
Garcia-Segura
Luis-Miguel
LM
Naftolin
Frederick
F
D000818:Animals; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D030762:Estrous Cycle / Q000378:metabolism*; D005260:Female; D006062:Gonadotropins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020644:Midline Thalamic Nuclei / Q000378:metabolism; D023421:Models, Animal; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism; D013569:Synapses / Q000502:physiology
D004967:Estrogens; D006062:Gonadotropins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D012333:RNA, Messenger; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D004958:Estradiol; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases; C525848:ST8SiaIV protein, mouse