Estrogen induction of sexual behavior in female rats and synthesis of polyadenylated messenger RNA in the ventromedial nucleus of the hypothalamus.

To test the hypothesis that estrogen stimulates sexual behavior by inducing transcription of polyadenylated messenger RNA, we studied the effects of cordycepin, an adenosine analog that disrupts polyadenylation, on the lordotic responses of ovariectomized female rats made sexually receptive with systemic injections of estradiol benzoate (EB) and progesterone (P). Cordycepin inhibited lordosis when infused into the ventromedial nucleus of the hypothalamus within an hour before the females received EB; its effectiveness varied linearly with dose. It did not significantly alter sexual behavior when infused into the medial preoptic area. A dose of cordycepin that decreased lordosis when infused 1 h before injection of 0.5 microgram EB did not affect the behavior when infused 1 h before injection of 500 micrograms P. Cordycepin does not suppress behavior by blocking estrogen uptake since it did not alter estrogen accumulation by hypothalamic cell nuclei. Cordycepin inhibits ribosomal RNA (rRNA) synthesis as well as polyadenylation. While this probably contributes to cordycepin's inhibitory effects on lordosis, it cannot fully account for them since a cytidine analog that inhibits rRNA synthesis without inhibiting polyadenylation did not mimic cordycepin's behavioral effects. Cordycepin may suppress synthesis of P receptors; however, this could not fully account for its behavioral effects since cordycepin also inhibited lordosis when the P receptor was bypassed by substituting methysergide for P. As assessed by protein synthesis autoradiography, cordycepin's effects are highly localized. The data support the notion that estrogen facilitates female sexual behavior by altering gene expression in the brain.