Effect of pindolol on the l-5-htp-induced increase in plasma prolactin and cortisol concentrations in man

Previous studies with direct-acting serotonin (5-HT) agonists and antagonists have demonstrated that stimulation of 5-HT_1A, 5-HT_1C and 5-HT₂ receptors may promote cortisol and prolactin (PRL) secretion in man. There is also evidence that 5-HT_1C/2 receptor stimulation contributes to the cortisol and PRL responses following administration of the 5-HT precursor, l-5-hydroxytryptophan (l-5-HTP), in man. To clarify the possible contribution of 5-HT_1A receptor stimulation to the ability of l-5-HTP to stimulate cortisol and PRL secretion in man, the effect of pindolol, a beta adrenoceptor antagonist that is also a 5-HT_1A partial agonist, on the l-5-HTP-induced increases in cortisol and PRL secretion, was examined in 12 normal male volunteers. Pretreatment with pindolol, 30 mg orally, significantly inhibited the PRL but not the cortisol response to l-5-HTP, 200 mg PO. Pindolol alone decreased basal plasma PRL levels and increased basal plasma cortisol levels, possibly due to 5-HT_1A antagonist and agonists effects, respectively. These data, coupled with observations from other studies, suggest that the l-5-HTP-induced increase in PRL but not cortisol secretion requires 5-HT_1A receptor activation. PRL secretion due to 5-HT formed from exogenous l-5-HTP may require the availability of both intact 5-HT_1A and 5-HT₂/5-HT_1C receptors, since blockade of either receptor type inhibited the PRL response to l-5-HTP. The implication of this synergistic effect for interpretation of neuroendocrine studies involving the serotonergic system in man is discussed.