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Inhibition of pulsatile luteinizing hormone release by atrial natriuretic peptide and brain natriuretic peptide in the ovariectomized rat Zhang, Jin


Atrial natriuretic peptide (ANP) of atrial myocyte origin, has been shown to play a role in the diuresis, natriuresis, and antagonism of angiotensin and vasopressin. However, it is now apparent that in addition to the production of the peptide in the heart and in its role in fluid and electrolyte homeostasis, it is also produced in the central nervous system participating in the regulation of pituitary hormone secretion. Administration of ANP through both central and peripheral routes has been shown to inhibit secretion of luteinizing hormone (LH) in the gonadectomized rat model. A better understanding of the modulatory role of ANP on LH secretion and its possible mechanisms will add to our knowledge of the effects of neuropeptides on reproductive function. Brain natriuretic peptide (BNP) is a bioactive peptide of 26 amino acid residues recently identified in porcine brain. The peptide exerts potent diuretic-natriuretic and vasorelaxant effects, in a manner similar to that of ANP. BNP has a remarkable high sequence homology to ANP, especially in the 17 amino acid ring formed by an intramolecular disulfide linkage which is required for biological activity. The presence of BNP with ANP in the mammalian brain and remarkable resemblance in their molecular structures and physiological functions implies that BNP may also exert an inhibitory effect on LH secretion like ANP. This research focused on the effects of centrally administered ANP and BNP on pulsatile LH secretion and their possible mechanisms of action in ovariectomized rats. After third ventricle infusion of ANP or BNP, inhibition of mean plasma LH level, LH pulse amplitude and pulse frequency was observed. In searching for the possible mechanisms of inhibitory effect of ANP or BNP on pulsatile LH secretion, the effect of inhibiting the endogenous opiate system with naloxone on the action of centrally administered ANP or BNP was tested. Application of naloxone reversed the inhibitory effect of ANP and BNP on mean plasma LH level and LH pulse amplitude, but in terms of pulse frequency, naloxone treatment failed to reverse the inhibitory effect of ANP or BNP. In separate experiments, pretreatment with pimozide, a dopaminergic receptor blocker, prevented the inhibitory action of ANP and BNP on LH secretion. After infusion of ANP or BNP, there were no significant decrease in mean plasma LH level, pulse amplitude and pulse frequency in the pimozide-pretreated rats. In summary, the present study shows that both ANP and BNP inhibit pulsatile LH secretion, suggesting that the inhibitory effects on LH secretion once thought to be mediated by ANP alone may be regulated through a dual mechanism involving both ANP and BNP. Furthermore, the inhibitory mechanisms may involve the interactions of ANP and BNP with central opiate system and dopaminergic system on LH secretion.

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