pituitrin and Hyperprolactinemia

Prolactin (PRL) stimulates the secretion of oxytocin (OXT) and arginine AVP as part of the maternal adaptations facilitating parturition and lactation. Both neurohormones are under the regulation of nitric oxide. Here, we investigate whether the activation of neuronal nitric oxide synthase (nNOS) in the hypothalamo-neurohypophyseal system mediates the effect of PRL on OXT and AVP release and whether these effects operate in males. Plasma levels of OXT and AVP were measured in male rats after the intracerebroventricular injection of PRL or after inducing hyperprolactinemia by placing two anterior pituitary glands under the kidney capsule. NOS activity was evaluated in the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei by NADPH-diaphorase histochemistry and in hypothalamic extracts by the phosphorylation/inactivation of nNOS at Ser(847). Elevated central and systemic PRL correlated with increased NOS activity in the PVN and SON and with higher OXT and AVP circulating levels. Notably, treatment with 7-nitroindazole, a selective inhibitor of nNOS, prevented PRL-induced stimulation of the release of both neurohormones. Also, phosphorylation of nNOS was reduced in hyperprolactinemic rats, and treatment with bromocriptine, an inhibitor of anterior pituitary PRL secretion, suppressed this effect. These findings suggest that PRL enhances nNOS activity in the PVN and SON, thereby contributing to the regulation of OXT and AVP release. This mechanism likely contributes to the regulation of processes beyond those of female reproduction.

Topics: Animals; Enzyme Inhibitors; Hyperprolactinemia; Indazoles; Injections, Intraventricular; Male; Neurons; Nitric Oxide Synthase Type I; Oxytocin; Paraventricular Hypothalamic Nucleus; Phosphorylation; Prolactin; Rats; Rats, Wistar; Supraoptic Nucleus; Vasopressins

Eleven patients with chronic hyperprolactinemia were tested to determine their osmotic threshold by isovolemic infusion of 5% NaCl. The results obtained demonstrate no statistical difference from known values in healthy volunteers. No linear correlation was found between levels of blood prolactin and the osmotic threshold, except for 1 patient who represents downward resetting of the hypothalamic osmoreceptors. The average time elapsed from the maximal dilution point to the osmotic threshold in hyperprolactinemia was found to be significantly shorter than in the normal population. We conclude that prolactin does not appear to participate in the osmotic regulation in man.

Topics: Adolescent; Adult; Bromocriptine; Female; Humans; Hyperprolactinemia; Infusions, Parenteral; Male; Prolactin; Sodium Chloride; Vasopressins; Water-Electrolyte Balance