Prolactin studies in normals: implications for clinical research

Dopaminergic (DA) transmission is a major regulator of pituitary prolactin (PRL) secretion. Strategies to assess abnormalities of DA regulation in mental illness have thus included comparisons of patients' and normals' serum PRL levels before and after the administration of DA agonists and antagonists. These clinical research strategies suffer from a number of shortcomings. There is a wide interindividual variability of normal basal PRL levels, and intraindividual variability has been little studied. Large interindividual variability of PRL responses to DA antagonist challenges has also been observed in normals and reported to be strongly correlated to variation in serum levels of the challenge drug. Assessment of DA agonist challenges is hampered by the fact that low basal levels of serum PRL make suppression difficult to measure; a further problem is the confounding effect of nausea when these drugs are given in high doses. In this study of normals, individual basal serum PRL levels were found to be stable over a mean period of 10 months, with interindividual variance vastly greater than intraindividual variance. Thus, state alterations in mental illness may best be studied using a longitudinal design for measurements of PRL levels in patients, thereby avoiding confounding interindividual variability. Moreover, it appears that alterations of PRL levels between groups or within patients, even though within the normal range, may have individual physiological significance. A study of the PRL responses to haloperidol (hal) and hal + apomorphine (apo) challenges in normals revealed a strong correlation despite a highly significant 51% reduction in PRL response with the addition of apo. Because this correlation is dependent upon a normal or limited range of DA regulation, the study of these two responses in abnormal populations may be more revealing of DA abnormalities than the study of PRL responses to single DA agonist or antagonist challenges.