Hypothalamic effects of C-type natriuretic Peptide on luteinizing hormone secretion

Previous studies have demonstrated hypothalamic sites of action of A-type natriuretic peptide (ANP) in the inhibition of luteinizing hormone (LH) secretion, acting at least in part, via an opiatergic mechanism. C-type natriuretic peptide (CNP) was identified recently and is thought to be the predominant brain form of the family of natriuretic peptides. Third cerebroventricular injection of CNP in doses of either 0.1, 1.0 or 2.0 nmole significantly inhibited, in a dose-related fashion, plasma LH levels when compared to levels present in saline-injected controls. When compared to the LH-inhibiting action of ANP, CNP appeared more potent (effective at lower doses) and efficacious (longer duration of action for the maximum effective doses). The LH-inhibiting effect of CNP was blocked by prior treatment with the δ-opioid receptor antagonist naltrindole (50 μg), suggesting an enkephalinergic mechanism of action. CNP in log doses ranging from 0.01 to 1,000 nM did not significantly alter LH release from dispersed pituitary cells harvested from random cycle female rats, either under static or dynamic (perifusion) incubation conditions. These results indicate that CNP, like ANP, acts at the hypothalamic level to alter LH secretion and suggest that CNP may be the preferential neuroactive members of this family of peptides.