Acute oral administration of selective serotonin re-uptake inhibitors (SSRIs) increases plasma cortisol by facilitating brain serotonin activity. Recently, salivary cortisol sampling has grown in popularity as a noninvasive means of assessing HPA axis activity. The aim of the present study was to find out whether acute oral administration of the SSRI, citalopram, increases salivary cortisol in healthy volunteers and whether the increase produced by an equivalent dose of its active isomer, escitalopram, is greater. A total of 15 healthy subjects were tested on three occasions receiving either oral citalopram (20 mg), escitalopram (10 mg), or placebo in a double-blind, randomized, crossover design. Salivary cortisol and plasma cortisol and prolactin were measured for 240 min after each treatment. Relative to placebo, both citalopram and escitalopram increased salivary and plasma cortisol levels with no evidence of consistent differences between them. Plasma prolactin concentration was not altered by either active treatment. Plasma and salivary cortisol responses after citalopram but not escitalopram correlated significantly. The present study does not support an enhanced effect of escitalopram on 5-HT-mediated neuroendocrine responses.

We studied the effect of the selective serotonin reuptake inhibitor (SSRI), paroxetine, on basal plasma prolactin concentrations in 11 healthy subjects. Subjects were tested before paroxetine, and after 1 and 3 weeks of treatment (20 mg daily). On each test occasion prolactin levels were sampled before and following administration of a placebo capsule, for a total of 4 h. After 3 weeks paroxetine treatment plasma prolactin levels were significantly higher than those seen either pre-treatment or after 1 week of treatment. In contrast, 1 week of paroxetine treatment did not significantly increase prolactin concentrations over pre-treatment values. Plasma concentrations of paroxetine did not differ between 1 and 3 weeks of treatment. The secretion of plasma prolactin is, in part, under the tonic regulation of serotonergic pathways and the present results therefore support animal experimental data suggesting that SSRIs produce a delayed increase in some aspects of brain serotonin neurotransmission.

We critically reviewed controlled investigations of the growth hormone releasing hormone (GHRH) stimulation test in depression, anorexia nervosa, bulimia, panic disorder, schizophrenia, and Alzheimer's disease. Comparisons of GH responsiveness between patients and controls within each diagnostic category were equivocal and in some cases contradictory. Factors that may contribute substantially to the inconsistent findings within diagnostic categories include (1) the variability of GHRH-simulated GH among control groups; (2) the lack of uniformity in test procedures and outcome measures; and (3) the age and gender of subjects. In addition, the individual reproducibility of the GHRH stimulation test has not been adequately investigated and until the test's stability within subjects can be determined, the validity of interpretations resulting from the GHRH simulation test are in question.

The effects of the optically active enantiomers of oxaprotiline (OXP), R(-) OXP and S(+) OXP, on depressive symptomatology and the sleep EEG were investigated in two separate exploratory studies. In addition, the neuroendocrine profile of both compounds was characterized in normal controls. In the patients treated with a daily oral dose of 150 mg S(+) OXP we found a Hamilton depression score that decreased from 29.1 +/- 1.8 (SEM) on day 0 to 14.7 +/- 3.2 on day 28 (P < 0.01). Six patients were judged to be full responders (HAMD score 0-7 points), three were improved (HAMD score 8-15) and four were nonresponders (HAMD score > 16). The therapeutic effect achieved with 150 mg R(-) OXP daily was less pronounced: the HAMD score decreased from 27.8 +/- 2.5 on day 0 to 19.4 +/- 3.2 on day 28 (P < 0.05). There were two full responders, one improved patient and seven nonresponders. The sleep EEG scoring revealed a marked suppression of REM sleep among patients treated with S(+) OXP but not with R(-) OXP. In the normal controls, a single oral dose of 75 mg S(+) OXP prompted an increase in the secretion of cortisol and growth hormone, whereas 75 mg R(-) OXP did not. Neither enantiomer influenced the secretion of testosterone or prolactin.

Neuroendocrine probes of serotonergic function are based on the premise that serotonin (5-HT) exhibits an excitory influence on the release of certain anterior pituitary hormones and that the extent of release of these hormones following a challenge with a 5-HT agonist would provide an index of central 5-HT activity. This paper critically reviews studies published to date on healthy volunteers to assess the validity of tests of serotonergic function. Using standardized criteria, it is concluded that although extensive data is available on 5-HT-neuroendocrine probes, there is no test that is currently available that would fulfil all the proposed requirements for a test to be acceptable, although ipsapirone, m-chlorophenylpiperazine (m-CPP), and possibly fenfluramine challenge tests come very close. The rapid development and availability of more specific and stereo-selective 5-HT agonists/antagonists seem to indicate that it will not be too long before a valid neuroendocrine test for the assessment of serotonergic function emerges.

Twelve patients with DSM-III-R major depressive illness were tested for growth hormone (GH) response to desipramine (DMI), a noradrenergic (NA) reuptake inhibitor. The response is mediated by NA alpha 2 receptors. They were then randomly assigned to treatment under double-blind conditions with either fluoxetine, the highly selective serotonin reuptake inhibitor or placebo. After 4 weeks they were retested. Fluoxetine but not placebo was effective in promoting recovery in four of the six patients treated. Patients treated with fluoxetine showed a significant decrease in DMI-mediated GH release irrespective of therapeutic outcome. This is consistent with marked alteration of NA function and raises questions as to the selectivity of fluoxetine.

Tricyclic antidepressants have been used frequently as pharmacological probes in neuroendocrine studies even though they appear to lack neurochemical specificity. Despite this, the hormonal responses to these drugs have been used to provide evidence that depressed patients have alterations in both noradrenergic and serotonergic tone within the central nervous system. Most studies have been conducted in the morning, which is not a time of high physiological neuroendocrine secretory activity. The present study has used the relatively specific serotonergic probe intravenous clomipramine given to depressed patients and healthy subjects immediately before sleep onset, which is a time of increased neuroendocrine activity. Under these conditions, 12.5 mg clomipramine stimulates the secretion of both cortisol and prolactin, but unlike studies conducted in the morning, clomipramine suppresses the secretion of growth hormone in both groups. These data suggest that serotonergic mechanisms are involved in the regulation of the secretion of these three hormones at the time of sleep onset.

Eight female patients who fulfilled DSM-III criteria for posttraumatic stress disorder (PTSD) took part in this study. They were each assessed using the dexamethasone suppression test, the desipramine/growth hormone stimulation test, which examines alpha-2-adrenoceptor functioning, and the buspirone/prolactin test, which is thought to examine 5-HT receptor functioning. A control group consisting of age- and sex-matched healthy subjects was also tested. For each subject the three tests were conducted over 5 days. Hormone assays were carried out blind to diagnosis. Overall no differences on any of the three tests were detected between the patients and controls. The results do not support a link between PTSD and major depression.

Desipramine, a monoamine reuptake inhibitor, was used to stimulate release of growth hormone (GH) in 29 DSM-III major depressives and in 10 healthy controls. Eighteen of the depressives showed a blunted response. The GH-stimulation test was unable to distinguish endogenous from non-endogenous patients. The 13 dexamethasone non-suppressors were more likely to have a blunted GH response than the 14 suppressors. The results indicate that at least a subset of non-endogenous depressives have significant neuroendocrine abnormality.

Thirty drug-free patients fulfilling the DSM-III criteria for major depression serially underwent the dexamethasone suppression test (DST), thyroid stimulating hormone (TSH) test and a growth hormone (GH) challenge test with oral desipramine. Fifty-three per cent of the sample showed a blunted GH response, 47% were DST non-suppressors while 26% had a blunted TSH response. Eighty per cent of patients showed some biological abnormality. There was no clear association between any of these abnormalities. Neither was there any association between the neuroendocrine parameters studied and the severity of depression or patient gender. There was a trend for increasing GH blunting and DST non-suppression with increasing age.

Desipramine, the monoamine reuptake inhibitor, acts predominantly on noradrenergic neurones, and via alpha-2 receptors brings about the release of growth hormone in normal healthy subjects. Thirteen patients with a diagnosis of irritable bowel syndrome, 10 normal controls and eight patients with peptic ulcer disease were each given a challenge test of desipramine 1 mg/kg body weight. Growth hormone release over a 3 h period was monitored. A blunted response was defined as a failure of growth hormone levels to rise at least 5 mU/l above baseline. Of the 13 patients with irritable bowel syndrome 11 showed such a blunting. The results suggest abnormal central alpha-2 receptor functioning in irritable bowel syndrome.

We report herein the effects of the beta-adrenergic agonist clenbuterol on desipramine (DMI)-induced growth hormone (GH), prolactin (PRL) and cortisol secretion in healthy male subjects. In the first study, nine subjects were treated with either clenbuterol (0.04 mg, p.o.) or placebo. In the second study, 12 subjects received either DMI (50 mg, i.v.) alone or in combination with clenbuterol (0.04 mg, p.o.) given 60 min prior to DMI administration. Clenbuterol alone had no influence on GH, PRL, or cortisol concentrations, compared to placebo. DMI alone caused GH stimulation (mean maximum = 15.7 +/- 3.4 ng/ml), which was significantly lower after combined administration of DMI and clenbuterol (mean maximum = 7.7 +/- 1.6 ng/ml) (p less than or equal to 0.01). DMI-induced PRL and cortisol stimulation was not influenced by clenbuterol pretreatment. These results indicate the inhibiting influence of noradrenergic beta-receptors on GH stimulation.

This study was undertaken to assess the value of growth hormone (GH) response to clonidine as a tool in the differential diagnosis between depression and dementia. This response is known to be blunted in depression, and neurochemical changes observed in senile dementia of the Alzheimer type (SDAT) could lead to an up-regulation of GH secretion. No difference was observed between GH response in depressed and demented patients. Together with studies on GH basal secretion in Alzheimer's disease, this finding suggests that the final consequence of SDAT-related changes in an accentuation of the effects of aging on GH reactivity.

Serial blood samples were collected from 15 elderly depressed inpatients, ages 62 to 95 years, following random assignment to a 50 mg oral test dose of desmethylimipramine (DMI) or amitriptyline (AMI). Nine female and six male subjects began the 210-min study at 0800h. Serum growth hormone (hGH), cortisol, and prolactin (hPRL) were determined by radioimmunoassay. Baseline hormone concentrations were related to self and observer ratings of anxiety and depression. There was a trend for the hGH, cortisol, and hPRL concentrations to decline during the period of study. This trend for all three hormones reversed in those subjects receiving DMI, beginning approximately 90 min after drug ingestion. The DMI-induced increase of hGH reached statistical significance at the very end of the sampling period. There was an apparent latency in the DMI-induced effect for all three hormones. There was no stimulatory effect of AMI on hGH, cortisol, or hPRL. The female subjects had higher baseline hGH levels than the men. In addition, a significant negative correlation was found between baseline hPRL levels and self ratings of anxiety.

Desipramine 75 mg i.m. was given in the morning to 20 adolescents with major depressive disorder and 23 normal controls. Depressed adolescents secreted significantly less growth hormone (GH) over the next 2 h than did normal adolescents, although a substantial proportion of the differences were accounted for by the depressed adolescents who had a specific suicidal plan or attempt during the episode. Severity of depression or the presence of other depressive symptoms did not predict GH secretion within the depressed group. Age, sex and maturational factors in the control of GH are discussed. It is concluded that these differences in GH secretion probably reflect differences in CNS beta-adrenergic and/or serotonergic function. Suicidality and depression may have different psychobiological correlates in adolescents.

Plasma prolactin (PRL) and growth hormone (GH) were serially measured over a 5-hour morning period in healthy subjects who twice received a single oral dose of 100 mg desipramine (DMI). The study was carried out both after a regular night of sleep and after 1 night of total sleep deprivation. Clinical studies have suggested that sleep deprivation could potentiate the therapeutic effects of antidepressants, and there were reports on DMI stimulation of GH. The basal PRL levels decreased after sleep deprivation, but subsequently increased after DMI, whereas the same dose of DMI did not affect PRL in the absence of after DMI, whereas the same dose of DMI did not affect PRL in the absence of sleep deprivation. The GH levels increased substantially (8- to 10-fold) after DMI in both experimental conditions. Sleep deprivation neither changed GH basal levels nor potentiated the DMI-induced GH increase.

The release of growth hormone, prolactin and cortisol following oral imipramine was studied in nine fit young men. Imipramine 100 mg, but not 40 mg, led to reliable rises in the circulating levels of all three hormones in the majority of subjects. These responses are likely due to the enhancement of central noradrenergic and serotonergic function as a result of reuptake inhibition. The safety, sensitivity and reliability of these responses make imipramine 100 mg orally a potentially valuable neuroendocrine challenge test.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced growth hormone (GH) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). DMI-induced GH stimulation was not significantly different after DMI i.v. alone (n = 12) than after three days' pretreatment with 12 mg methysergide p.o. in another group of subjects (n = 12). Following combined administration of DMI and propranolol (15 mg i.v.), GH secretion was significantly increased by 25 mg DMI (p less than 0.05) and 50 mg DMI (incomplete block design, n = 18). GH secretion was significantly lower (p less than 0.01) after DMI in combination with 60 mg phentolamine i.v. compared to that after administration of DMI alone in the same group (n = 12). Following 10 mg yohimbine i.v. in combination with DMI (n = 6), the DMI-induced GH increase was also significantly less (p less than 0.05) than that after DMI alone. The DMI-induced GH increase following DMI plus 1 mg prazosin p.o. (n = 12) was comparable to that after DMI alone. The results indicate that the GH-stimulating effect of DMI is primarily related to the ability of DMI to inhibit noradrenaline (NA) reuptake. Should serotonergic receptors be involved in the DMI-induced GH secretion at all, they transmit a positive stimulus. The alpha-1 receptors are most likely not (or not essentially) involved, whereas alpha-2 receptors affect the DMI-induced secretion positively, and beta receptors have an inhibitory effect.

In this report the effects of various receptor blockers on desimipramine (DMI)-induced prolactin (PRL) secretion in healthy male subjects are presented. Each trial consisted of two administrations: one of DMI i.v. alone and one of DMI i.v. in combination with the respective receptor blocker: methysergide (serotonin (5-HT) receptor blocker), propranolol (beta receptor blocker), phentolamine (alpha-1/alpha-2 receptor blocker), yohimbine (alpha-2 greater than alpha-1 receptor blocker), and prazosin (alpha-1 receptor blocker). Following administration of methysergide (12 mg p.o., n = 12), a significantly lower (p less than 0.01) DMI-induced PRL secretion compared to DMI alone in another group of subjects (n = 12) was observed. Combined administration with propranolol (15 mg i.v.) significantly enhanced the DMI-induced PRL secretion compared to DMI 50 mg i.v. alone (n = 18, incomplete block design) (p less than 0.01). Neither combined administration with phentolamine (60 mg i.v., n = 12), yohimbine (10 mg i.v., n = 6), nor prazosin (1 mg p.o., n = 12) significantly influenced the DMI-induced PRL secretion compared to DMI alone in the same subjects. The results of the present study, especially the inhibitory effect on DMI-induced PRL secretion of methysergide, indicate that the primarily noradrenaline (NA) and lesser serotonin (5-HT) reuptake inhibiting antidepressant DMI stimulates PRL secretion via 5-HT neurons. Furthermore, the significantly enhanced PRL release following combined administration of DMI and propranolol suggests that a noradrenergic inhibitory effect also may be involved in the transmission of the PRL stimulus.

The effect of i.m. administration of 75 mg of desipramine on growth hormone (GH) secretion was investigated in a sample of 87 patients with major depressive disorders and in 31 normal controls. The GH response was lower in depressed females compared to depressed males, but no such difference was present in controls. In the premenopausal female group, GH response was significantly lower in depressed patients than in controls. No significant difference was found between normal males and male depressed patients. In the premenopausal group, no difference emerged between endogenous and nonendogenous depressed women.

Plasma cortisol levels were monitored for 2 hours after an intramuscular injection of 75 mg desipramine in 13 endogenous depressives and 20 normal controls. Endogenous depressives had a significantly reduced cortisol response in comparison to normal controls, not explained by sex, age, or baseline cortisol differences between groups. A lack of a cortisol rise of 1.5 micrograms/dl above baseline by 45 minutes discriminated best, with 7 of 13 depressives (55%) being identified in contrast to only 1 of 20 normals (5%). The results suggest that this may be a useful biological test with acceptable sensitivity (55%) and excellent specificity (95%). Furthermore, these data suggest that norepinephrine may be stimulatory to cortisol in man.

In previous studies it was shown that the tricyclic antidepressant desimipramine (DMI) had different stimulatory effects on growth hormone (GH), prolactin (PRL), ACTH and cortisol secretion in healthy subjects, depending on the mode of administration. The present study examined the effects following i.v. administration of placebo and DMI (5, 15, 25, 50 and 75 mg) on GH, PRL and cortisol secretion in male subjects (n = 6). This primarily noradrenergic and secondarily serotonergic reuptake-inhibiting substance was found to stimulate the secretion of GH, PRL and cortisol in a dose-dependent manner. Compared to placebo, significant increases occurred in GH (p less than 0.05) and in PRL (p less than 0.05) from a dose of DMI 25 mg on, and in cortisol (p less than 0.05) from 15 mg on. The results indicate that, in addition to the dose, the method of administration influenced the effects of DMI on the three hormones.

In order to compare the effects of chlorimipramine (CI) and desimipramine (DMI) on growth hormone (GH) and on prolactin (PRL) secretion equal doses of 25 mg CI or DMI were administered i.v. to 12 healthy subjects each. In this dose, DMI, which primarily inhibits norepinephrine (NE) uptake, induced a significantly higher GH stimulation, compared to CI, whereas CI, which primarily inhibits serotonin (5-HT) uptake induced a significantly higher PRL stimulation, compared to DMI. Following DMI administration, an increase in GH (greater than 7.5 ng/ml) was found in all subjects, after CI in only about 50% of the subjects. The varying interindividual GH secretions after CI are discussed on the basis of the different plasma levels of CI and of its metabolite desmethyl-chlorimipramine (DCI), which is a NE uptake-inhibitor.

Spontaneous prolactin patterns were determined at 15-min intervals over 5 h in 13 patients, who were suffering from melancholia, during illness and after treatment with amitriptyline. Plasma prolactin levels were significantly greater at most sampling points after patients had recovered than during their illnesses. One patient, who did not recover, showed the opposite trend.

The effect of bupropion HCL (Wellbatrin), a new anti-depressant, on the secretion of GH and PRL in healthy male subjects and male hyperprolactinaemic patients was studied. The study was a randomised double-blind test in which 6 subjects and 6 patients who had been treated with neuroleptics were each, in accordance with the random plan, treated once with placebo and once with 200 mg bupropion p.o.. After administration of the test substance, blood was drawn to measure bupropion, GH and PRL up to 240 minutes thereafter. Neither in the healthy men nor in the patients could a specific effect of bupropion on the secretion of GH be shown in comparison to placebo although bupropion in all subjects and patients was well reabsorbed. As opposed to the results of Stern et al. (5), no change in the secretion of PRL was measured in either the healthy subjects or the hyperprolactinaemic patients. In addition, no change in the TRH-induced stimulation of PRL could be measured. The results of the present study offer no positive contribution towards an explanation of the mechanism of bupropion.

Single doses of the antidepressant amitriptyline were given to 12 normal males. After parenteral or oral dose of the drug, the concentration of growth hormone in plasma rose in one third of the subjects. Amitriptyline could have multiple and potentially opposite pharmacological actions on growth hormone. Antidepressants appear to be poor pharmacological tools for assessing the regulation of growth hormone release.

Phentolamine, a postsynaptic noradrenergic (NA) receptor blocker, inhibits diazepam-induced growth hormone (GH) secretion in man. In order to study the effect of phentolamine on six healthy subjects with a diazepam (10 mg i.v.)-induced GH increase greater than 7.5 ng/ml, it was necessary to test 11 subjects. The six diazepam GH responders showed a significantly higher (p less than 0.01) GH stimulation after diazepam alone than after diazepam plus phentolamine (60 mg i.v.). The inhibitory effect of phentolamine suggests that NA alpha receptors are involved in the diazepam-induced GH increase. Prolactin secretion after administration of diazepam (10 mg i.v.) was only slightly elevated in comparison with placebo (i.v.), suggesting that diazepam does not have an agonistic effect on dopamine (DA) receptors.

(1) The dexamethasone suppression test (DST) was utilized to study the aldosterone (Aldo) response in patients with endogenous depression (ED). This adrenal steroid is believed to be regulated by CNS factors different from ACTH. (2) Six female patients (two pre- and four post-menopausal) and six female healthy controls (three pre-and three post-menopausal) were studied under equivalent conditions. Venous blood samples were taken at 0900 and 2300 hr before and at 0900, 1600 and 2300 hr after dexamethasone (2 mg p.o.) given at 2300 hr. In healthy controls, the median of plasma Aldo at 0900 hr before dexamethasone was lower than at 0900 hr after drug administration (p less than 0.01), while the opposite change occurred in the patients. The median of the controls at 0900 hr post-dexamethasone was 101 pg/ml, and that of the patients was 23 pg/ml (p less than 0.025). (3) According to these observations dexamethasone appears to have a stimulatory effect on 0900 hr plasma Aldo-levels, which are blunted in patients with ED. This finding possibly signifies disinhibited central dopaminergic function in ED. Whether dopamine acts directly on the adrenal gland or modulates Aldo secretion via Aldo-releasing factors different from ACTH remains unresolved. The neurotransmitter process which underlies Aldo regulation appears to be substantially altered in ED.

A comparison of the effect on growth hormone (GH) stimulation in men (n = 6) of desimipramine (DMI), a tricyclic antidepressant, and of the benzodiazepine derivatives diazepam and metaclazepam with that of a placebo, showed that only DMI caused a significant (p less than 0.01) GH stimulation. After DMI, all six subjects showed a GH stimulation greater than 7.5 ng/ml, whereas after diazepam or metaclazepam, only three of the six subjects showed GH stimulation greater than 7.5 ng/ml, and the other three showed only a very small change, or no change at all in GH secretion. Higher GH stimulation occurred after diazepam (10 mg i.v.) than after diazepam (10 mg p.o.). No dose-dependent difference in GH stimulation after metaclazepam (10 and 30 mg p.o.) was apparent. No side effects appeared after administration of DMI during the test period (180 min); however, after administration of the benzodiazepine derivatives, sedative effects were clearly noted. DMI thus causes reliable GH stimulation in healthy male subjects, whereas GH stimulation could only be measured in some of the subjects after diazepam and metaclazepam.

Eight depressed patients with major affective illness were treated with both zimelidine, a selective serotonin-uptake inhibitor, and with desipramine, a selective norepinephrine uptake inhibitor, following a double-blind crossover design. At steady-state the active metabolite of zimelidine, norzimelidine, predominated in the CSF by a factor of 7 to 1 over parent drug. As predicted, even high concentrations of norzimelidine were not associated with decreased 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the CSF. In the same individuals, desipramine concentrations were highly correlated with decreases of MHPG in the CSF. Despite specific effects on monoamine neurotransmitter systems which have been implicated in the control of neuroendocrine secretion, neither drug had consistent effects on plasma cortisol, luteinizing hormone, growth hormone or prolactin. Both drugs had a marked and unexpected common effect on the 24-hour rest-activity cycle. The excess activity during the normal rest period (0--700 hr.) which has been noted in severely depressed individuals was significantly reduced by both the serotonergic zimelidine and the noradrenergic desipramine. These findings suggest that effects on the rest-activity pattern may be a common pathway for antidepressant effect.

The biochemical research of depression did not gain in before the exploration of the nodes of effect of the antidepressants. For the present the point of research was the search for disturbances in metabolism of the biogenic amines in brain. The noradrenalin and serotonin-hypothesis was propounded postulating a disturbance in noradrenalin, or serotonin regulation, respectively at the receptor in depression. Until now experimental results did not support this hypothesis, just as the investigations of electrolytic changes in depression did not lead to homogeneous results. On the contrary the neuroendocrinological research showed important results; In endogenous depressive patients an increased cortisol-secretion was ascertained, and in about 65% of the patients a missing or strongly reduced cortisol-suppression after injection of dexamethason was noted, moreover, the growth-hormone-secretion after insulin-hypoglycemia is reduced in a part of depressive women in the menopause. Finally the thyrotropin-secretion stopped in 20--40% of the endogenous depressive patients after injection of thyrotropin-releasing hormone.

Human prolactin (hPRL) is the most recent anterior pituitary hormone in human endocrinology, whose structure has been elucidated in 1977. The possibility to measure hPRL in serum has led to a rapid increase of our knowledge of prolactin-physiology and -pathophysiology in men. hPRL is the only anterior pituitary hormone which is under predominantly inhibitory hypothalamic control. The effects of prolactin in the various species differ considerably, whereas in men it acts mainly upon the mammary gland and the gonadal system. Hyperprolactinemia leads typically to hypogonadism, amenorrhea and frequently galactorrhea. The hyperprolactinemia-hypogonadism-syndrome has been identified as a separate entity in recent years. Because of the relative frequency of this disease prolactin measurements have become of great importance in the diagnosis of sterility. Depending on the cause of hyperprolactinemia a neurosurgical, radiotherapeutical or medical treatment is indicated.