Insulin-like growth factor-1 regulation of alpha(1)-adrenergic receptor signaling is estradiol dependent in the preoptic area and hypothalamus of female rats

Recently, we demonstrated that estradiol (E-2) modulates cross-talk between protein tyrosine kinases and norepinephrine (NE) receptor signaling in the hypothalamus (HYP) and preoptic area (POA), brain areas that govern female reproductive function. We are now investigating the identity of protein ty rosine kinase(s) that modify NE receptor signaling in the HYP and POA. Incu bation of POA and HYP slices with insulin-like growth factor I (IGF-I), whi ch signals via a receptor (IGF-IR) with endogenous tyrosine kinase activity , enhances NE-stimulated cAMP accumulation only in tissue derived from ovar iectomized, E-2-primed animals. JB-1, an antagonist for IGF-IR, pre vents t he IGF-I enhancement of NE-stimulated cAMP accumulation in both POA and HYP slices. IGF-I enhances NE-stimulated cAMP accumulation via modulation of a lpha (1)-adrenoceptor potentiation of adenylyl cyclase. Binding studies in membranes demonstrate that ovariectomized, E-2-primed animals show a signif icant increase in the density of [I-125]IGF-I-binding sites in both POA and HYP compared with ovariectomized control animals. Neither the IC,, for [I- 125]IGF-I dig placement by IGF-I nor the levels of IGF-I binding proteins i n serum or brain tissue are affected by E-2. RIA results showed that E-2 do es not modify serum or brain IGF-I levels. These results indicate that E-2 regulation of NE receptor function in the POA and HYP involves increased ex pression of IGF-IR, and that after E-2 treatment, IGF-IR activation augment s alpha (2)-adrenoceptor signaling.