Human chorionic gonadotropin induces nestin expression in endothelial cells of the ovary via vascular endothelial growth factor signaling.
The intermediate filament protein nestin was originally found to be expressed in neuronal progenitor cells, but recent studies have shown that other cell types, including endocrine and vascular endothelial cells, express nestin. In the present study, we examined the expression and localization of nestin in the ovaries of developing, peripubertal, and adult rats. RT-PCR and Western blot analyses revealed that nestin mRNA and proteins were expressed in adult rat ovaries. Immunohistochemical analyses using adult rat ovaries showed that nestin was mainly localized to capillary endothelial cells of theca interna in follicles with more than two layers of granulosa cells and that its expression increased with follicle growth. Ontogenetically, ovarian nestin expression started at the peripubertal period when the first gonadotropin surge occurs. To test the possibility that gonadotropins induce nestin expression, prepubertal (postnatal d 21) rats were sc injected with equine chorionic gonadotropin (eCG) and/or human chorionic gonadotropin (hCG). A single injection of hCG, but not eCG, was sufficient to induce nestin expression in follicles, mainly in capillary endothelial cells of theca interna. Furthermore, pretreatment with an inhibitor of vascular endothelial growth factor receptor prevented the induction of the nestin expression by hCG. These findings demonstrate that the endogenous LH surge induces nestin expression in capillary endothelial cells of theca interna via the vascular endothelial growth factor signaling pathway. Nestin may be involved in angiogenesis in growing follicles, which is followed by follicle maturation and subsequent ovulation.
Takahashi
Noriyuki
N
Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan. n-tkhs@marianna-u.ac.jp
Itoh
Masanori T
MT
Ishizuka
Bunpei
B
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D064231:Nestin; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010053:Ovary / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D010060:Ovulation / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013799:Theca Cells / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
D006063:Chorionic Gonadotropin; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D042461:Vascular Endothelial Growth Factor A