|Direct effects of nerve growth factor on thecal cells from antral ovarian follicles.|
|PMID: 11108289 Owner: NLM Status: MEDLINE|
|TrkA, the nerve growth factor (NGF) tyrosine kinase receptor, is expressed not only in the nervous system, but also in nonneural cells, including discrete cellular subsets of the endocrine and immune system. In the rat ovary, trkA receptor abundance increases strikingly in thecal-interstitial cells during the hours preceding the first ovulation. Blockade of either trkA transducing capacity or NGF biological activity inhibited ovulation, suggesting a role for NGF in the ovulatory process of this species. To identify some of the processes that may be affected by trkA activation in the thecal compartment, we used purified thecal cells/thecal fibroblasts from bovine ovaries (heretofore referred to as thecal cells). Ribonuclease protection assays employing bovine-specific cRNA probes demonstrated the presence of the messenger RNAs (mRNAs) encoding NGF and its receptors, p75 NTR and trkA, in the thecal compartment of small, medium, and large antral follicles and showed that trkA mRNA is also expressed in granulosa cells. In situ hybridization and immunohistochemical examination of intact ovaries confirmed these cellular sites of NGF and trkA synthesis. TrkA mRNA, but not NGF mRNA, was lost within 48 h of placing thecal cells in culture. Thus, to study trkA-mediated actions of NGF on these cells we transiently expressed the receptor by transfection with a vector containing a full-length rat trkA complementary DNA under transcriptional control of the cytomegalovirus promoter. Because ovulation is preceded by an LH-dependent increase in androgen and progesterone production, the ability of NGF to modify the release of these steroids was determined in freshly plated cells still containing endogenous trkA receptors and in cells undergoing luteinization in culture that were transiently transfected with the trkA-encoding plasmid. NGF stimulated both androgen and progesterone release in freshly plated thecal cells, but not in luteinizing cells provided with trkA receptors. As ovulation in rodents requires an increased formation of PGE2 and has been shown to be antedated by proliferation of thecal fibroblasts, we determined the ability of NGF to affect these parameters in trkA-transfected thecal cells. The neurotrophin rapidly stimulated PGE2 release and amplified the early steroidal response to hCG in trkA-expressing cells, but not in cells lacking the receptor. Likewise, NGF stimulated [3H]thymidine incorporation into trkA-containing cells, but not into cells that had lost the receptor in culture. Induction of ovulation in immature rats by gonadotropin treatment verified that an increased cell proliferation in the thecal compartment, determined by the incorporation of bromodeoxyuridine into cell nuclei, occurs 4-5 h before ovulation in this species. These results suggest that the contribution of NGF to the ovulatory process includes a stimulatory effect of the neurotrophin on steroidogenesis, PGE2 formation, and proliferative activity of thecal compartment cells.|
|G A Dissen; J A Parrott; M K Skinner; D F Hill; M E Costa; S R Ojeda|
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|Type: Journal Article; Research Support, U.S. Gov't, P.H.S.|
|Title: Endocrinology Volume: 141 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 2000 Dec|
|Created Date: 2000-12-06 Completed Date: 2000-12-22 Revised Date: 2009-11-19|
Medline Journal Info:
|Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: UNITED STATES|
|Languages: eng Pagination: 4736-50 Citation Subset: AIM; IM|
|Division of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton 97006-3448, USA. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
Cell Division / drug effects
Chorionic Gonadotropin / pharmacology
Dinoprostone / metabolism, secretion
In Situ Hybridization
Isoenzymes / genetics
Nerve Growth Factor / genetics, pharmacology*
Ovarian Follicle / cytology*
Ovulation / drug effects
Progesterone / secretion
Prostaglandin-Endoperoxide Synthases / genetics
RNA, Messenger / analysis
Receptor, Nerve Growth Factor / genetics
Receptor, trkA / genetics, physiology
Receptors, Nerve Growth Factor / genetics
Theca Cells / cytology, drug effects*, physiology
|HD-24870/HD/NICHD NIH HHS; HD-33372/HD/NICHD NIH HHS; U-54-HD-18185/HD/NICHD NIH HHS|
|0/Chorionic Gonadotropin; 0/Isoenzymes; 0/RNA Probes; 0/RNA, Messenger; 0/Receptor, Nerve Growth Factor; 0/Receptors, Nerve Growth Factor; 363-24-6/Dinoprostone; 57-83-0/Progesterone; 63-05-8/Androstenedione; 9061-61-4/Nerve Growth Factor; EC 220.127.116.11/Cyclooxygenase 2; EC 18.104.22.168/Prostaglandin-Endoperoxide Synthases; EC 22.214.171.124/Receptor, trkA|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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