Alpha-2-Adrenergic Control of Prolactin Release

The role of the α2-adrenergic system in regulating prolactin release has been studied in vivo in male rats. Yohimbine administration alone, at doses ranging from 0.2 to 5.0 mg/kg, resulted in a dose-releated elevation of plasma prolactin levels from a basal level of 8 ± 2 to 65 ± 6 ng/ml at the highest dose. In the same experiment clonidine, 0.2 mg/kg, suppressed basal prolactin levels to 4+ 1 ng/ml and returned prolactin levels of all animals receiving 0.2–5.0 mg/kg yohimbine to basal levels. Rats were treated with increasing doses of clonidine (0.05–1.0 mg/kg) in the presence or absence of a constant dose (1.0 mg/kg) of yohimbine. Clonidine alone at doses of 0.05 and 0.2 mg/kg again significantly suppressed prolactin levels, while a dose of 1.0 mg/kg did not (failure of high dose clonidine to suppress prolactin levels suggests an additional effect of clonidine on prolactin secretion unrelated to α2-adrenergic agonist action). All three doses of clonidine completely reversed yohimbine-induced prolactin release. Basal prolactin levels were also significantly reduced by the selective α2-adrenergic agonist UK-14,304 at a dose of 0.2 mg/kg. Yohimbine-induced prolactin release was reversed by UK-14,304 at doses of 0.2 and 1.0 mg/kg, but not at the lowest dose studied, 0.05 mg/kg. The lower potency of UK-14,304 than clonidine in this assay is consistent with the lower potency of UK-14,304 as an α2-adrenergic-agonist antihypertensive agent. Several α2-antagonists in addition to yohimbine were studied. Both Wy-26,703 and piperoxan administration resulted in elevated plasma prolactin levels; these effects were reversed by clonidine treatment. A 3-fold reduction in prolactin levels was observed in the hyperprolactinemic state of lactating rats following a 0.2 mg/kg dose of clonidine. Our data demonstrate that the α2-adrenergic system is involved in inhibiting prolactin release since (1) α2-agon-ists lower basal prolactin levels, (2) α2-antagonists elevate prolactin levels, and (3) prolactin levels not different from basal ones are observed when appropriate doses of agonists and antagonists are administered in combination.