BLOCKADE OF NORADRENERGIC NEUROTRANSMISSION WITH DIETHYLDITHIOCARBAMIC ACID DECREASES THE MESSENGER-RNA LEVEL OF GONADOTROPIN-RELEASING-HORMONE IN THE HYPOTHALAMUS OF OVARIECTOMIZED, STEROID-TREATED PREPUBERTAL RATS

We have previously found that progesterone (P) augmented gonadotropin- releasing hormone (GnRH) mRNA levels in the hypothalamus of ovariectom ized, estradiol-treated (OVX+E) prepubertal rats. In order to determin e whether noradrenergic neurotransmission is involved in the stimulato ry effect of P on GnRH gene expression, diethyldithiocarbamic acid (DD C, 500 mg/ kg), a dopamine beta-hydroxylase inhibitor was administered i.p. 1 h before P (1 mg) injection into OVX+E treated rats, and the e ffect of DDC on the P-induced GnRH mRNA levels was examined. A single injection of P into OVX+E primed rats augmented norepinephrine (NE) co ntent, while the administration of DDC effectively blocked the P-induc ed increase in NE content, along with the increase in dopamine content . Suppression of NE neurotransmission with DDC resulted in a marked de crease in the P-induced GnRH mRNA levels as well as GnRH release in vi tro. These results clearly demonstrate that noradrenergic neurotransmi ssion is involved in P-stimulated GnRH gene expression in the rat hypo thalamus.