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The tonic inhibition of prolactin (PRL) secretion, which appears to be sustained mainly by hypothalamic dopaminergic activity, can be reliably disinhibited by neuroleptic, antidopaminergic drugs. The heuristic potential of this PRL response as a neuroendocrine model for studying hypothalamicpituitary regulation in man initiated the present intensive investigation.Nineteen normal young men were studied in a series of weekly experiments; at each session a single drug and dose, out of seven neuroleptic drugs in various doses, was given parenterally (mostly im). Plasma PRL concentrations were then monitored for at least 3 h. 1. Repeated administrations of haloperidol (1 mg im) and prochlorperazine (4 mg iv) demonstrated a high reproducibility of the PRL response within a subject. 2. The PRL-response to four doses of haloperidol, ranging from 0.25 mg to 1.5 mg, showed a sigmoid dose-response curve. A dose as small as 1.5 mg of haloperidol induced maximal PRL response. 3. Dose-PRL response curves of haloperidol, prochlorperazine, and thiothixene, representing three chemical classes of neuroleptic drugs, showed a parallel relationship. This suggests a common pharmacological, very likely antidopaminergic, mechanism of the drugs when releasing PRL. 4. In response to haloperidol (1 mg), chlorpromazine (25 mg), and trifluoperazine (4 mg), plasma PRL concentrations remained elevated for at least 7 h, consistent with reported plasma half-lives of these drugs. 5. Dose equivalencies of seven neuroleptic drugs in inducing PRL secretion in man are given.The presented data indicate that the PRL response to neuroleptic drugs is sensitive and reliable and is probably a valid test of dopaminergic blockade in man. Our findings suggest a model for studying drug and hormonal interactions with neuroleptics in man. (J Clin Endocrinol Metab 45: 996, 1977)

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Interest in possible neuroendocrine disturbances in endogenous depression is prompted by two lines of evidence: (1) clinical features of the illness suggest hypothalamic dysfunction; (2) the brain neurotransmitters implicated in depression also regulate neuroendocrine function. Our research reveals a marked, sustained hypersecretion in cortisol in severe depressive illness, which is apparently unrelated to stress and sleep disturbance, and which is associated with a distortion of the 24-hour cortisol secretory pattern. The hypersecretion is manifested primarily in the late afternoon, evening, and early morning hours, when cortisol secretion is normally inhibited. Growth hormone responses to hypoglycemia (but not to L-dopa) are also significantly reduced in endogenous depression, even when factors of age and the menopause are controlled. Postmenopausal depressed women appear to secret significantly less LH than normal postmenopausal women. Since all of these hormonal abnormalities can be reproduced by depletion of brain noradrenalin, the findings provide support for the the hypothesis of reduced functional noradrenergic activity in certain forms of depression.