This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dissen, G. A. Articles by Ojeda, S. R. Search for Related Content PubMed PubMed Citation Articles by Dissen, G. A. Articles by Ojeda, S. R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB TESTOSTERONE

Intraovarian Excess of Nerve Growth Factor Increases Androgen Secretion and Disrupts Estrous Cyclicity in the Rat¹

Division of Neuroscience (G.A.D., D.F.H., M.E.C., S.R.O.), Oregon Regional Primate Research Center-Oregon Health Sciences University, Beaverton, Oregon 97006-3448; Laboratory of Neurobiochemistry, Faculty of Chemistry and Pharmaceutical Sciences (H.E.L., A.P.), Faculty of Medicine (V.L.),Universidad de Chile, Santiago Chile; and Center of Molecular Biology Severo Ochoa (A.M.S.), Autonomous University of Madrid, 28049 Cantoblanco, Spain

Address all correspondence and requests for reprints to: Gregory A. Dissen, Division Neuroscience, Oregon Regional Primate Research Center, 505 N.W. 185th Avenue, Beaverton, Oregon 97006-3448. E-mail: disseng{at}ohsu.edu Address all requests for NGF cells to: Dr. A.

A single injection of estradiol valerate induces a form of cystic ovary resembling some aspects of the human polycystic ovarian syndrome. Preceding the development of follicular cysts, there is an increase in intraovarian synthesis of nerve growth factor (NGF) and the low affinity NGF receptor (p75 NGFR). Selective blockade of NGF actions and p75 NGFR synthesis in the ovary restored estrous cyclicity and ovulatory capacity in estradiol valerate-treated rats, suggesting that an increase in NGF-dependent, p75 NGFR-mediated actions within the ovary contributes to the development of cystic ovarian disease. We have tested this hypothesis by grafting NGF-producing neural progenitor cells into the ovary of juvenile rats that have been induced to ovulate precociously by a single injection of PMSG. The NGF-producing cells, detected by their content of immunoreactive p75 NGFR material, were found scattered throughout the ovary with some of them infiltrating the granulosa cell compartment of large, precystic follicles. Ovarian NGF content was 2-fold higher than in the ovary of rats receiving control cells. Estrous cyclicity was disrupted, with the animals showing prolonged periods of persistent estrus, and an almost continuous background of vaginal cornified cells at other phases of the estrous cycle. Morphometric analysis revealed that the presence of NGF-producing cells neither reduced the total number of corpora lutea per ovary nor significantly increased the formation of follicular cysts. However, the ovaries receiving these cells showed an increased incidence of precystic, type III follicles, accompanied by a reduced number of healthy antral follicles, and an increased size of both healthy and atretic follicles. These changes in follicular dynamics were accompanied by a selective increase in serum androstenedione levels. The results show that an abnormally elevated production of NGF within the ovary suffices to initiate several of the structural and functional alterations associated with the development of follicular cysts in the rat ovary.

This article has been cited by other articles:

				Y. B. Sverrisdottir, T. Mogren, J. Kataoka, P. O. Janson, and E. Stener-Victorin Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E576 - E581. [Abstract] [Full Text] [PDF]

				C. Parra, J. L Fiedler, S L. Luna, M. Greiner, V. Padmanabhan, and H. E Lara Participation of vasoactive intestinal polypeptide in ovarian steroids production during the rat estrous cycle and in the development of estradiol valerate-induced polycystic ovary Reproduction, January 1, 2007; 133(1): 147 - 154. [Abstract] [Full Text] [PDF]

				L. Manni, A. Holmang, S. Cajander, T. Lundeberg, L. Aloe, and E. Stener-Victorin Effect of anti-NGF on ovarian expression of {alpha}1- and beta2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R826 - R835. [Abstract] [Full Text] [PDF]

				R. A. Anderson, L. L. L. Robinson, J. Brooks, and N. Spears Neurotropins and Their Receptors Are Expressed in the Human Fetal Ovary J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 890 - 897. [Abstract] [Full Text] [PDF]

				M. Bilger, S. Heger, D. W. Brann, A. Paredes, and S. R. Ojeda A Conditional Tetracycline-Regulated Increase in Gamma Amino Butyric Acid Production near Luteinizing Hormone-Releasing Hormone Nerve Terminals Disrupts Estrous Cyclicity in the Rat Endocrinology, May 1, 2001; 142(5): 2102 - 2114. [Abstract] [Full Text]

				H. E. Lara, G. A. Dissen, V. Leyton, A. Paredes, H. Fuenzalida, J. L. Fiedler, and S. R. Ojeda An Increased Intraovarian Synthesis of Nerve Growth Factor and Its Low Affinity Receptor Is a Principal Component of Steroid-Induced Polycystic Ovary in the Rat Endocrinology, March 1, 2000; 141(3): 1059 - 1072. [Abstract] [Full Text] [PDF]