Mechanisms of Dopaminergic Regulation of Prolactin Secretion

Abstract

Dopamine has been recognized as the primary regulator of prolactin (PRL) secretion in vivo for over 20 years (1,2). Hypothalamic dopamine is secreted from tuberoinfundibular neurons at the median eminence of the hypothalamus into the hypophyseal portal blood flow, which directly perfuses the pituitary gland, delivering dopamine at high concentration to anterior pituitary cells. Several lines of evidence suggested that PRL, unlike other pituitary hormones, is under primarily inhibitory hypothalamic regulation, and that dopamine acts as the mediator. Interrupting the portal blood flow to the pituitary by pituitary stalk section results in elevated PRL secretion. The hypersecretion of PRL of the isolated pituitary was reversed by pituitary grafting to an intact portal blood flow (3); by perfusion with hypothalamic extracts containing PIF (PRL inhibitory factor) activity, which was subsequently found to contain dopamine as the active principle (3,4); and by perfusion with dopamine itself (4,5). Dopamine antagonists (e.g., haloperidol) are known to induce hyperprolactinemia and block the PRL-inhibitory actions of dopamine (6,7). Ultimately, dopamine levels measured in portal blood were shown to be sufficient to inhibit PRL secretion in vitro (8),firmly establishing dopamine as the PIF, the only nonpeptide hypothalamic hormone. Thus, tonic inhibition of PRL secretion by dopamine controls the level of PRL in the organism: Decreasing dopamine release leads to enhanced PRL release, mediated in part by stimulatory hormones such as thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). Enhancement of PRL release correlates with low hypophyseal portal dopamine concentration and is most pronounced during proestrous-estrous, pregnancy, and lactation in the female. The secreted PRL participates in breast and uterine development and milk generation in the breast. In males, PRL levels are low in part because of an absence of circulating estrogen, a powerful inducer of PRL gene transcription (1,2). The present chapter summarizes the current understanding of the mechanisms by which dopamine regulates hormone secretion from the pituitary, focusing primarily on dopaminergic inhibition of PRL secretion.KeywordsPotassium ChannelVasoactive Intestinal PeptidePituitary CellProlactin SecretionAnterior Pituitary CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.