Functional interactions between estrogen and insulin-like growth factor-I in the regulation of α1B-adrenoceptors and female reproductive function

Abstract

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 E2 treatment 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 treated in vivo with vehicle or E2 daily 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 E2 injection. Administration of JB-1 during E2 priming 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 E2 priming 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 E2 treatment. These events may help coordinate the timing of ovulation with the expression of sexual receptivity.