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Biomedical subjects

R T Rubin

Publications and source records attributed to R T Rubin.

At least 109 records · Page 6Linked to original sources

Intravenous infusion of beta-endorphin increases serum prolactin, but not growth hormone or cortisol, in depressed subjects and withdrawing methadone addicts.

In a randomized, double blind, cross-over study, human beta-endorphin or saline was infused iv over 30 min into six depressed psychiatric patients and four methadone addicts. All depressed subjects showed prompt, 2- to 4-fold increases in serum PRL levels, which lasted at least 2 h. The addicts, who were undergoing acute methadone withdrawal, showed similar PRL increases, which were dose dependent. beta-Endorphin did not increase serum levels of cortisol or GH in either group of subjects. These results suggest that iv beta-endorphin has potent but selective neuroendocrine effects in depressed patients and subjects withdrawing from methadone.

Adult↗

The effect of nursing on neurohypophyseal hormone and prolactin secretion in human subjects.

The effect of nursing on plasma levels of oxytocin (OT), arginine vasopressin (AVP), and PRL was studied in six normal women 2-3 days post partum. Maternal blood samples were obtained for measurement of OT, AVP, PRL, sodium, and osmolality 3 and 0 min before suckling, at 3-min intervals for 15 min during suckling, and 5 min after completion of suckling. Plasma OT rose during suckling from a mean (+/- SEM) baseline value of 1.1 +/- 0.2 to 3.6 +/- 0.6 microU/ml by 3 min (P < 0.001), reached a peak level of 6.4 +/- 1.5 microU/ml by 6 min (P < 0.005), and remained elevated for the entire 15-min period of suckling. Serial measurements of plasma OT during suckling failed to show a pattern consistent with episodic secretion. The baseline plasma AVP concentration was 0.4 +/- 0.1 microU/ml and was not significantly altered by suckling. Plasma sodium and osmolality remained unchanged during the suckling period. The baseline serum PRL level was 268 +/- 24 ng/ml and rose to 362 +/- 31 ng/ml after 15 min of suckling (P < 0.05). The data suggest that suckling is a specific stimulus for OT and PRL secretion but has no effect on AVP release.

Arginine Vasopressin↗

Prolactin releasing potencies of antipsychotic and related nonantipsychotic compounds in female rats: relation to clinical potencies.

Prolactin responses to various intraperitoneal doses of nine antipsychotic and related nonantipsychotic compounds were measured in the sera of female rats. At doses of 50 mg/kg or less, all drugs stimulated prolactin. Dose-response curves indicated the following order of prolactin stimulating potency: haloperidol greater than reduced haloperidol congruent to lenperone greater than chlorpromazine greater than AHR-1900 greater than thioridazine greater than clozapine greater than U-25927 greater than SCH-12679. This ranking does not agree entirely with the ranking of relative antipsychotic potency of these compounds. The butyrophenone AHR-1900 is inactive clinically, whereas clozapine is a more potent antipsychotic agent than chlorpromazine. The relation between prolactin-stimulating potency and reported clinical potency was improved by comparing drugs within the same chemical classification: AHR-1900 was only one-sixtieth as potent as haloperidol in stimulating prolactin secretion. Reduced haloperidol, a major metabolite of haloperidol, was one-fourth as potent as haloperidol in stimulating prolactin release, suggesting that the potential antipsychotic activity of reduced haloperidol should be investigated.

Animals↗

Variability of prolactin response to intravenous and intramuscular haloperidol in normal adult men.

Serum prolactin (PRL) concentrations were monitored in seven normal adult men for 1 h before and 7 h after i.v. and i.m. injection of 0.25 mg and 0.50 mg haloperidol. The magnitude of the PRL response was dose-related but quite variable across subjects. The patterns of PRL secretion over the 7 h post-injection period also varied greatly among the subjects. Differences in serum heloperidol concentrations accounted for 88% of the variability in the magnitude of the PRL response to the 0.5 mg IM haloperidol dose, but only accounted for 60% of the PRL variability following the 0.5 mg IV dose. The pattern of haloperidol disappearance from serum was similar across the seven subjects and thus unrelated to the variable patterns of PRL response.

Adult↗

Postnatal maturation patterns of serum corticosterone and growth hormone in rats: effect of chronic thyroxine administration.

The effects of chronic neonatal hyperthyroidism in rats on the ontogenic pattern of serum corticosterone and growth hormone (GH) were studied. Thyroxine (T4) treated and saline injected rat pups were sacrificed under basal and stress conditions. In comparison to saline control animals, daily T4 administration (0.4 micrograms/gram body weight) produced a sustained elevation in basal corticosterone levels by day 12 and a significant elevation of serum corticosterone in response to stress by day 4. The serum GH levels in non-stressed animals were moderately decreased in response to T4 administration as compared to saline injected animals with a greater reduction in GH measured in samples obtained from stressed animals. The results indicate that chronic T4 administration influences the developmental pattern of serum corticosterone and GH under both non-stress and stress conditions.

Aging↗

Effect of chronic metoclopramide therapy on serum pituitary hormone concentrations.

The effect of chronic (3--9 months) therapy with metoclopramide on serum levels of pituitary and thyroid hormones was studied in 4 males and 1 female. The mean serum prolactin concentration during metoclopramide therapy was significantly higher than after discontinuation of metoclopramide. Serum prolactin concentrations increased acutely after each dose of metoclopramide. Serum prolactin concentrations increased acutely after each dose of metoclopramide, and gradually returned to normal by 6--12 h. There was no sifgnificant differences in the serum TSH, T3, T4, GH, and gonadotrophin levels during and after metoclopramide administration. In the male subjects the mean serum testosterone was normal, but significantly lower during metoclopramide therapy.

Adult↗

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.

Adolescent↗

Failure of nocturnal prolactin suppression by methysergide to entrain changes in testosterone in normal men.

In order to investigate further the postulated relationship between the secretion of PRL and testosterone, 10 normal young men were studied during polygraphically recorded sleep. Concentrations of LH and testosterone were measured in plasma every 20 min, and the results were analyzed in relation to sleep parameters and previously reported (J Clin Invest 56: 690, 1975) concentrations of PRL. All subjects were studied on a control night after placebo administration and on an experimental night after ingestion of the serotonin receptor blocker, methysergide. Analysis of variance revealed that concentrations of testosterone rose gradually during sleep on both nights, as has been noted in previous studies. Highest LH values occurred during stage 1 sleep, but were only 25% higher than the lowest values, which were seen in stage 4. As shown previously, PRL concentrations were markedly suppressed by methysergide treatment. However, no significant change in testosterone values were observed on the methysergide nights as compared to the control nights. When the data were analyzed by a correlational approach, again, no significant relation between concentrations of PRL and testosterone was found. Although these data do not support the concept that PRL-stimulated testosterone secretion occurs during the night in normal men, this study does not rule out the possibility that such a mechanism may be operative during daytime hours, or under conditions of PRL stimulation rather than PRL suppression.

Humans↗

Influence of methyl-TRH-induced prolactin increase on serum testosterone levels in normal adult men.

Our previous studies suggest that increased serum PRL, secondary to haloperidol-induced dopamine blockade, augments serum testosterone (T) levels in normal men. To rule out a direct effect of haloperidol on the testis, serum samples from a methyl-TRH study in normal men, in whom serum PRL levels were increased by a stimulus other than dopamine blockade, were analyzed for T. Fourteen subjects received both a low dose (6.25-12.5 micrograms) and a high dose (100-500 micrograms) of methyl-TRH on separate days; blood sampling was done for 15 min before and for 4 h after drug infusion. Compared to a saline control group of 14 normal men, who showed a diurnal decline of serum T levels, the methyl-TRH treated subjects had statistically significant increases in serum T after both low and high doses. These data provide further support for the concept that PRL is a pituitary hormone capable of augmenting serum T levels in normal adult men.

Adult↗

Lack of arginine vasopressin response to central dopamine blockade in normal adults.

Haloperidol, a central nervous system dopamine blocker, was given im to seven normal volunteers at a dose level (1.0 mg) known to have central nervous system effects. Plasma PRL levels rose sharply in response to haloperidol, but plasma arginine vasopressin levels did not change significantly. These data do not support the hypothesis of a prominent dopamine neurotransmitter regulation of arginine vasopressin secretion.

Adult↗

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.

Adult↗