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Am J Physiol Regul Integr Comp Physiol 290: R826-R835, 2006. First published September 29, 2005; doi:10.1152/ajpregu.00078.2005
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

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

Luigi Manni,1,2 Agneta Holmäng,1 Stefan Cajander,3 Thomas Lundeberg,4 Luigi Aloe,2 and Elisabet Stener-Victorin1,5,6

1Cardiovascular Institute, Wallenberg Laboratory, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden; 2Institute of Neurobiology and Molecular Medicine, Consiglio Nazionale delle Ricerche, Rome, Italy; 3Department of Pathology and Cytology, Akademiska Sjukhuset, Uppsala; 4Rehabilitation Medicine, Danderyds Hospital, Stockholm; and 5Department of Obstetrics and Gynecology and 6Institute of Occupational Therapy and Physical Therapy, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden

Submitted 4 February 2005 ; accepted in final form 26 September 2005

Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats are associated with higher ovarian release and content of norepinephrine, decreased beta2-adrenoceptors (ARs), and dysregulated expression of {alpha}1-AR subtypes, all preceded by an increase in the production of ovarian NGF. The aim of this study was to further elucidate the role of NGF in the ovaries by blocking the action of NGF during development of EV-induced PCO in rats. Control and EV-injected rats were treated with intraperitoneal injections of IgG (control and PCO groups) or with anti-NGF antibodies (anti-NGF and PCO anti-NGF groups) every third day for 5 wk starting from the day of PCO induction. Rat weight, estrous cyclicity, ovarian morphology, ovarian mRNA, and protein expression of {alpha}1-AR subtypes, beta2-AR, the NGF receptor tyrosine kinase A (TrkA), p75 neurotrophin receptor (p75NTR), and tyrosine hydroxylase (TH) were analyzed. Ovaries in both PCO and PCO anti-NGF groups decreased in size as well as in number and size of corpora lutea. mRNA expression of {alpha}1a-AR and TrkA in the ovaries was lower, whereas expression of {alpha}1b- and {alpha}1d-AR and TH was higher, in the PCO group than in controls. Protein quantities of {alpha}1-ARs, TrkA, p75NTR, and TH were higher in the PCO group compared with controls, whereas the protein content of beta2-AR was lower. Anti-NGF treatment in the PCO group restored all changes in mRNA and protein content, except that of {alpha}1b-AR and TrkA mRNAs, to control levels. The results indicate that the NGF/NGF receptor system plays a role in the pathogenesis of EV-induced PCO in rats.

nerve growth factors; sympathetic nervous system; ovarian innervation; tyrosine kinase A; p75 neutrophin receptor



Address for reprint requests and other correspondence: L. Aloe, Institute of Neurobiology and Molecular Medicine (CNR), Via del Fosso di Fiorano 64, 00143 Rome, Italy (e-mail: aloe{at}inmm.cnr.it)







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