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Biomedical subjects

R T Rubin

Publications and source records attributed to R T Rubin.

At least 127 records · Page 7Linked to original sources

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.

Adult↗

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.

Adolescent↗

Optimal statistical design of radioimmunoassays and competitive protein-binding assays.

The statistical analysis of radioimmunoassay and competitive protein binding assay data is complex. Because the response variable (percent counts) is not lineraly related to log dose, a logit transformation of the response variable usually is performed to permit linear regression analysis. This transformation induces marked heterogeneity of variance, so that iterative weighted regression programs have been used to achieve the best standard curve and the most precise dose estimates of unknowns. In this study several parameters of assay design are investigated in order to establish those designs yielding antigen concentration estimates of highest precision as well as estimates of comparable precision by either simple linear regression analysis or by the more complex weighted regression technique. Unknown estimates of highest precision are obtained when 1) the present counts of the standard doses covers a range of approximately 80 percent to 20 percent, 2) the number of standard dose levels is eight or more, 3) the number of replicates at each dose level is two or more, and 4) the percent counts of the unknowns also are within the range 80 percent ot 20 percent. Under these conditions, also, simple linear regression yields unknown estimates of comparable precision to weighted regression and therefore may be safely used.

Antigens↗

Nocturnal increase of plasma testosterone in men: relation to gonadotropins and prolactin.

The nocturnal increase of plasma testosterone (T) in adult men has been well established. Luteinizing hormone (LH) does not show a similar increase throughout the night, whereas prolactin (PRL) does, suggesting the possibility of other hormone influence on T secretion. To investigate this possibility, 8 young adult men were studied for 4 consecutive nights in the sleep laboratory (2 nights adaptation, 2 nights blood sampling), by blood samples taken every 30 min during the 8-h sleep period, for measurement of LH, follicle stimulating hormone (FSH), PRL, and T. LH and FSH were secreted episodically, with little or no change in baseline levels during the night. PRL and T also were secreted episodically, but their baseline levels increased as the night progressed. Both LH and PRL had maximum within-subject correlations (averages equal +0.35 and +0.48 respectively) with T when they led T by 60 min. Within-subject correlations done on first differences (to remove the effect of slow trends) were near zero. LH and PRL had larger correlations with T than did FSH, for both calculations. These data suggest that both LH and PRL levels precede T levels by about 60 min. PRL thus may participate in the regulation of nocturnal T secretion in adult men.

Adult↗

Gonadotropin secretion during sleep in normal adult men.

Release of luteinizing hormone and follicle stimulating hormone during sleep in young adult men occurred in unrelated, random, arrhythmic peaks, with no consistency from night to night in the same subject. Release of luteinizing hormone was modestly but significantly larger (14 perecnt) during rapid-eye-movement sleep than it was in non-REM sleep, but release of follicle stimulating hormone was not clearly related to stages of sleep.

Adult↗