Prolactin-related testosterone secretion in normal adult men.

The sleep-related increase of plasma testosterone (T) in adult men appears to be related not only to plasma luteinizing hormone (LH) levels but to prolactin (PRL) levels as well, suggesting that PRL may have a stimulatory influence on Leydig cell function. To further investigate the influence of PRL on T secretion, five young adult men were studied on three separate days one week apart. Blood samples were taken every 20 min between 0900 and 1800. At 1000 on each of the three days they received an intramuscular injection of saline, haloperidol 0.25 mg or haloperidol 0.50 mg, in a double-blind design. The blood samples were analyzed for LH, follicle stimulating hormone (FSH), PRL and T. It was hypothesized that there would be a dose-related increase in both PRL and T following drug administration. Mean PRL levels rose promptly and significantly in a dose-related manner in response to the haloperidol, which has strong dopamine blocking effects. By 1600, PRL had returned to control values. In contrast to the PRL response, neither LH nor FSH levels were affected by haloperidol. On the saline control day mean T levels showed the normal decline during daytime hours. After 0.25 mg haloperidol, mean T levels were maintained for several hours, and after 0.50 mg haloperidol, T levels were increased for several hours. These alterations in the normal diurnal pattern of T were statistically significant. They began about 60 min after the corresponding drug-induced increases in PRL levels. This delay between increased PRL and increased T is consistent with the similar delay between the increases of these two hormones that occur at night during sleep. The results of this study lend further support to the hypothesis that PRL is another pituitary hormone that stimulates T secretion in adult men.

Effects of prolactin and prolactin plus luteinizing hormone on plasma testosterone levels in normal adult men.

In an earlier study, normal adult men were shown to have increased plasma testosterone (T) levels over a several-hour period after haloperidol-induced increases in plasma PRL levels. The present study was designed both to replicate our first study and to examine the potential synergism of PRL and LH in influencing T levels on a short term basis in normal men. Eight volunteers received on 4 separate days an in injection of saline or 0.5 mg haloperidol at 1000 h and an iv injection of saline or 88 IU human LH (hLH) at 1100 h in a double blind randomized block design arranged to augment plasma levels of PRL, LH, and PRL and LH together on the different test days as well as to afford a saline control day. Only five of the eight subjects had prompt PRL responses to haloperidol equivalent to those of our earlier study. As the purpose of this study was to examine the effect of increased PRL on plasma T levels, these five subjects were used for the determination of changes in plasma T. After haloperidol administration, their PRL levels rose an average of 19 ng/ml, to the high-normal range, and after the hLH infusions, their LH levels rose an average of 71 ng/ml. On the saline control day, mean T levels showed the normal diurnal decline. After 0.5 mg haloperidol, T levels were maintained for several hours, and after 88 IU hLH, T levels were increased for several hours. Increased PRL levels concomitant with hLH administration did not produce a T response greater than that caused by hLH alone. The results of this study replicate the effect of drug-induced PRL augmentation on plasma T levels found in our earlier study, but they fail to demonstrate a synergistic effect of acutely increased PRL on LH-stimulated T secretion. PRL thus seems to be another pituitary hormone capable of increasing plasma T in adult men, but it clearly is a weaker stimulus than LH.

Secretion of hormones influencing water and electrolyte balance (antidiuretic hormone, aldosterone, prolactin) during sleep in normal adult men.

Renal conservation of electrolytes and water occurs normally during sleep. Antidiuretic hormone (ADH), aldosterone (ALDO), and prolactin (PRL) are hormones that may have interactive effects on kidney function. The availability of a radioimmunoassay for ADH as well as for ALDO and PRL permitted the study of the simultaneous secretion patterns of these three hormones during all-night sleep in eight normal young adult men, by blood sampling every 20 min from 2300 to 0700 on two consecutive night. ADH, ALDO, and PRL all appeared to be secreted episodically. The pulsatile release of ADH was random, and average plasma ADH levels were unchanged during the night. ALDO and PRL, on the other hand, had an approximately 90-min secretion rhythm, and average plasma concentrations of both hormones consistently increased during the hours of sleep. Average plasma sodium concentration was constant throughout the night. The nocturnal increase in plasma ALDO may be responsible for the normal reduction of urine sodium excretion during the night. The concomitant increase in plasma PRL might synergize with ALDO in influencing the renal retention of sodium, but PRL alone has little apparent effect on human kidney function. REM sleep-related decreases in urine flow have been noted both in humans and in monkeys, but ADH secretion was not REM related in out subjects. Autonomic activation during REM is one possible explanation for decreased urine flow during this stage of sleep.

Selective neuroendocrine effects of low-dose haloperidol in normal adult men.

The neuroendocrine effects of haloperidol, usually reported as side effects of this drug when given in antipsychotic doses, have not been systematically investigated. In the present study five normal adult men were administered saline and two doses of of haloperidol (0.25 mg, 0.5 mg) intramuscularly in a double-blind randomized block design. The anterior pituitary hormones GH, LH, FSH, and PRL were measured in blood samples taken every 20 min for several hours thereafter. The low doses of haloperidol used have been shown by others to alter the human EEG; in our subjects these doses produced no objective or subjective clinical effects. There were no drug related changes in GH, LH, or FSH. PRL, however, showed a prompt, statistically significant, dose-related increase in plasma levels, with a return to baseline with 5 h. Haloperidol has strong dopamine-blocking effects, and the hypothalamic inhibitory mechanism for PRL release is believed to be dopamine-mediated. The results of this study suggest that haloperidol may have utility in low doses primarily for its hypothalamic neuroendocrine effects, and that dose-related PRL release may be a useful paradigm for comparing dopamine-blocking antipsychotic agents in humans.