Atrial Natriuretic Factor Inhibits Luteinizing Hormone Secretion in the Rat: Evidence for a Hypothalamic Site of Action*

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Abstract
The presence of atrial natriuretic factor (ANF) immunoreactivity and receptors for ANF in the median eminence, hypothalamus, and anterior pituitary gland suggests a role for the peptide in the hypothalamic control of anterior pituitary function. In conscious ovariectomized female rats, transient elevation of plasma levels of ANF by volume loading, a stimulus known to release endogenous ANF from the heart, or by bolus iv injection of 0.1, 1.0, or 10 .mu.g synthetic ANF failed to result in altered circulating levels of LH or GH. Constant iv infusion of ANF for 30 min, such that 2- to 3-fold elevations in plasma ANF were detected by RIA resulted, however, in significant inhibition of LH release in ovariectomized female rats (0.05 and 0.1 .mu.g ANF/kg .cntdot. min) and orchidectomized male rats (0.1 .mu.g ANF/kg .cntdot. min). It was unlikely that this effect was exerted at the level of the anterior pituitary, since ANF failed to alter basal or LHRH-stimulated LH release from cultured anterior pituitary cells in vitro and since iv infusion of 0.1 .mu.g ANF/kg .cntdot. min failed to alter pituitary responsiveness in vivo to a 10-ng bolus injection of LHRH. Significant inhibition of LH secretion was also observed after third cerebroventricular injection of 1.0 or 2.0 nmol ANF. As with iv infusion, central administration of ANF failed to significantly alter GH secretion. LHRH release from median eminence explants incubated in vitro in the presence of dopamine (60 or 120 .mu.M) was inhibited by 10-7 M ANF, suggesting a median eminence site of action of the peptide. Finally, an opiate involvement in the mechanism of ANF''s action was suggested, since naloxone (0.5 mg, iv, followed by a 60-min infusion of an additional 1 mg) completely blocked the ability of ANF (0.1 or 0.5 .mu.g/kg .cntdot. min, infused over the last 30 min of naloxone administration) to inhibit LH release. These data suggest that ANF can act centrally to alter the hypothalamic control of gonadotropin secretion, possibly by interacting with central dopaminergic and peptidergic systems. They further suggest action of ANF within the brain unrelated to its previously described effects on fluid and electrolyte homeostasis.