Effect of anti-NGF on ovarian expression of alpha1- and beta2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries.
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 alpha1-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 alpha1-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 alpha1a-AR and TrkA in the ovaries was lower, whereas expression of alpha1b- and alpha1d-AR and TH was higher, in the PCO group than in controls. Protein quantities of alpha1-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 alpha1b-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.
Manni
Luigi
L
Cardiovascular Medicine, Wallenberg Laboratory, Sahlgrenska Academy, Göteborg University, Sweden.
Holmäng
Agneta
A
Cajander
Stefan
S
Lundeberg
Thomas
T
Aloe
Luigi
L
Stener-Victorin
Elisabet
E
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives; D005260:Female; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C485843:Bex3 protein, rat; D009414:Nerve Growth Factors; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D004958:Estradiol; D014446:Tyrosine 3-Monooxygenase; D020917:Receptor, trkA