C-type natriuretic peptide mediates the hypothalamic actions of the natriuretic peptides to inhibit luteinizing hormone secretion.

Both A- and C-type natriuretic peptides (ANP and CNP, respectively) significantly reduce LH secretion when injected into the third cerebral ventricle of conscious rats. To establish which natriuretic peptide receptor subtype transduces these inhibitory messages, we have employed novel cytotoxin cell targeting techniques to selectively destroy cells in the hypothalamus that respond to ANP or CNP. Rats pretreated with ANP conjugated to the toxic A-chain of the plant cytotoxin ricin failed 1 week later to respond to central injection of ANP with the normal inhibition of LH secretion. These rats did, however, respond with significant inhibition of LH secretion to central injection of CNP. In fact, the LH inhibition observed after CNP injection was significantly greater than that expressed after similar injection of CNP in rats pretreated with unconjugated ricin A-chain (toxin control). Those control rats displayed significant reduction of LH levels in response to ANP injection as well. Plasma LH levels were not significantly affected by central administration of either ANP or CNP in rats pretreated with ricin A-chain conjugated to CNP. These results further demonstrate the power of this novel technology and provide positive evidence supporting our hypothesis that ANP exerts its LH-inhibiting effect by displacing endogenous CNP from clearance receptors within the brain. This endogenous CNP, then, like exogenously applied CNP, activates the guanyl cyclase-B receptors on cells, which are part of the network controlling the release of LHRH.