Submitted on February 4, 2005
Accepted on September 26, 2005
Effect of anti-NGF on the ovarian expression of 
1- and 
2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries
Luigi Manni1, Agneta Holmang2, Stefan Cajander3, Thomas Lundeberg4, Luigi Aloe5*, and Elisabet Stener-Victorin6
1 Sahlgrenska Academy, Goteborg University, Cardiovascular Institute, Wallenberg Laboratory, Goteborg University, Goteborg, Sweden; CNR, Institute of Neurobiology and Molecular Medicine, Rome, Italy
2 Sahlgrenska Academy, Goteborg University, Cardiovascular Institute, Wallenberg Laboratory, Goteborg University, Goteborg, Sweden
3 Akademiska sjukhuset, Department of Pathology and Cytology, Uppsala, Sweden
4 Danderyds Hospital, Rehabilitation Medicine, Stockholm, Sweden
5 CNR, Institute of Neurobiology and Molecular Medicine, Rome, Italy
6 Sahlgrenska Academy, Goteborg University, Cardiovascular Institute, Wallenberg Laboratory, Goteborg University, Goteborg, Sweden; Sahlgrenska Academy, Goteborg University, Department of Obstetrics and Gynecology, Goteborg, Sweden; Sahlgrenska Academy, Goteborg University, Institute of Occupational Therapy and Physical Therapy, Goteborg, Sweden
* To whom correspondence should be addressed. E-mail: aloe{at}inmm.cnr.it.
Estradiol valerate (EV)-induced polycystic ovaries(PCO)in rats are associated with ovarian higher releases and contents of norepinephrine (NE), decreased 
2-adrenoceptors (ARs), and dysregulated expression of 
1-AR subtypes, all of them preceded by an increase in the production of ovarian nerve growth factor (NGF). The aim of this study was to further elucidate the role of NGF on the ovaries by blocking the action of NGF during the development of EV-induced PCO in rats. Control and EV-injected rats were treated with intraperitoneal injections of IgG (control group and PCO group) or with anti-NGF antibodies (anti-NGF group and PCO anti-NGF group) every third day for 5 weeks starting from the day of PCO induction. Rat weight; estrous cyclicity; ovarian morphology; ovarian mRNA; and the protein expression of 1-AR subtypes, 2-AR, the NGF receptor tyrosine kinase A (TrkA), p75 neurotrophin receptor (p75NTR), and tyrosine hydroxylase (TH) were analyzed. The ovaries in both the PCO and the PCO anti-NGF groups decreased in size as well as in number and size of corpora lutea. The mRNA expression of 1a-AR and TrkA in the ovaries was lower while 1b- and 1d-AR and TH was higher in the PCO group than in controls. The protein quantities of the 1-ARs, TrkA, p75NTR, and TH were higher in the PCO group compared with the controls, while the protein content of 2-AR was lower. Anti-NGF treatment in the PCO group restored all changes in mRNA and protein content, except that of 1b-AR and TrkA mRNAs, to control levels. The results of the present study indicate that the NGF/NGF receptor system plays a role in the pathogenesis of EV-induced PCO in rats.
