EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON FOLLICLE GROWTH, OOCYTE MATURATION, AND OVARIAN STEROIDOGENESIS AND PLASMINOGEN-ACTIVATOR ACTIVITY IN THE RABBIT

We examined the effects of insulin-like growth factor (IGF)-I on folli cular growth, oocyte maturation, and ovarian steroidogenesis and plasm inogen activator (PA) activity in vitro, using a perfused rabbit ovary preparation in order to determine whether the follicle-stimulating ef fects of growth hormone (CH) are mediated by IGF-I. The addition of IG F-I to the perfusate stimulated follicular growth and the resumption o f meiosis in follicular oocytes in a dose-dependent manner. There was no significant difference in the production of progesterone by perfuse d rabbit ovaries between IGF-I-treated and control ovaries, whereas IC F-I increased the production of estradiol (E(2)) by perfused rabbit ov aries in a dose-dependent manner. The concomitant addition of a monocl onal antibody recognizing the type I ICF receptor, alpha IR-3, to the perfusate significantly blocked IGF-I-stimulated follicular growth, oo cyte maturation, and E(2) production. Intrafollicular PA activity incr eased significantly 4 h after exposure to 10 or 100 ng/ml of IGF-I and reached maximal levels at 6 h. The percentage increase in follicle di ameter at 6 h after exposure to ICF-I was significantly correlated wit h the intrafollicular PA activity. Treatment with Ctl resulted in a 2. 7-fold increase in intrafollicular levels of ICF-I mRNA. The binding o f [I-125]-IGF-I to rabbit ovarian membrane preparations was inhibited by unlabeled IGF-I and ICF-II in a concentration-dependent manner. The relative affinity of the IGF-I receptor for IGF-I, ICF-II, and insuli n was typical of type 1 binding (IGF-I > IGF-II > insulin). Affinity c ross-linking of ovarian membranes with [I-125]-IGF-I revealed a radiol abeled band corresponding to a molecular weight of 135 000, the alpha subunit of the type I IGF receptor. This band was totally displaced by IGF-I and alpha IR-3. It was concluded that IGF-I stimulated follicul ar development, E(2) production, and oocyte maturation by interacting with its specific receptor located in rabbit ovarian membranes.