The ovarian hormone estradiol (E2) and insulin-like growth factor-I (IGF-I) interact in the CNS to regulate neuroendocrine function and synaptic remodeling. Previously, our laboratory showed that 2 d E2treatment induces α1B-adrenoceptor expression and promotes IGF-I enhancement of α1-adrenoceptor potentiation of cAMP accumulation in the preoptic area (POA) and hypothalamus (HYP). This study examined the hypothesis that E2-dependent aspects of female reproductive function, including α1B-adrenoceptor expression and function in the POA and HYP, are mediated by brain IGF-I receptors (IGF-IRs) in female rats. Ovariohysterectomized rats were implanted with a guide cannula aimed at the third ventricle and treatedin vivowith vehicle or E2daily for 2 d before experimentation. Intracerebroventricular infusions of JB-1, a selective IGF-IR antagonist, were administered every 12 hr beginning 1 hr before the first E2injection. Administration of JB-1 during E2priming completely blocks hormone-induced luteinizing hormone release and partially inhibits hormone-dependent reproductive behavior. Reproductive behavior is restored by intracerebroventricular infusion of 8-bromo-cGMP, the second messenger implicated in α1-adrenergic facilitation of lordosis. In addition, blockade of IGF-IRs during E2priming prevents E2-induced increases in α1B-adenoceptor binding density and abolishes acute IGF-I enhancement of NE-stimulated cAMP accumulation in HYP and POA slices. These data document the existence of a novel mechanism by which IGF-I participates in the remodeling of noradrenergic receptor signaling in the HYP and POA after E2treatment. These events may help coordinate the timing of ovulation with the expression of sexual receptivity.