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Biomedical subjects

G A Mason

Publications and source records attributed to G A Mason.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effects of ethanol and control liquid diets on the hypothalamic-pituitary-thyroid axis of male Fischer-344 rats.

The effects of a high dextrose liquid diet containing ethanol and two different control liquid diets on serum and brain thyroid axis hormones and liver and brain deiodinase activities were studied in groups of adult male Fischer-344 (F-344) rats. Rats received either lab chow, ad libitum; a nutritionally complete 10% (w/v) ethanol liquid diet, ad libitum; a volume of either a high carbohydrate (HC) or a high fat (HF) isocaloric control liquid diet equal to the volume of diet consumed by rats given the ethanol diet; or the HC control diet, ad libitum. Consumption of liquid diets was measured daily and body weights recorded every other day throughout the study. Hormones were measured after 2, 4, or 8 weeks and deiodinase activities after 4 or 8 weeks. Also, groups of rats were given the 10% ethanol diet, ad libitum, or pair-fed the HC control diet intermittently for 8 weeks, and thyroid hormones and thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) were determined. Within 2 weeks rats became accustomed to all diets and thereafter weight gain was comparable in all groups. Small differences between serum thyroid hormones of rats fed the ethanol diet and pair-fed HC or HF controls may have been caused by lower T4 secretion in ethanol-fed rats. Marked differences in free and total T4 and T3 between F-344 rats fed liquid diets for 4 or 8 weeks and rats fed lab chow probably resulted from higher liver 5'-deiodinase activity in rats fed liquid diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1992

Attenuation of alcohol preference in alcohol-preferring rats by a novel TRH analogue, TA-0910.

Experiments were performed to characterize the acute effect of different doses of a novel thyrotropin-releasing hormone (TRH) analogue (TA-0910) on ethanol intake in rats. Selectively bred alcohol-preferring (P) rats received a single intraperitoneal injection of normal saline or 0.083, 0.25 and 0.75 mg/kg of TA-0910 at 9:30 AM, and their consumption of ethanol, water, and food was measured for 24 hr. TA-0910 dose-dependently attenuated ethanol intake and commensurately increased water consumption. Only the highest dose of TA-0910 increased the total caloric intake. TA-0910 did not affect the pharmacokinetics of ethanol. These findings indicate involvement of TRH systems in ethanol preference and suggest that centrally acting TRH analogues may be therapeutic in the treatment of alcoholism.

Alcohol Drinking↗
PubMed1992

Evidence for normal feedback inhibition of triiodothyronine on the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in abstinent male alcoholics.

Disturbances in the hypothalamic-pituitary-thyroid (HPT) axis have been reported in abstinent, noncirrhotic alcoholics, including a reduction in thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and reductions in triiodothyronine (T3). Some evidence has suggested that a portion of alcoholics may also exhibit a disturbance in the feedback inhibition of thyroid hormone on TSH release. To evaluate the function of the HPT axis negative feedback system in abstinent, noncirrhotic alcoholic men we compared the TSH response with TRH before and after a standard suppressive dose of T3. Ten alcoholic subjects were studied and compared with four control subjects from a previous study and to literature values. The mean percent reduction in TSH response in the alcoholic subjects of 74 +/- 7% was almost identical to the 71 +/- 9% reduction observed in normal subjects. The present findings indicate that noncirrhotic, abstinent alcoholic men exhibit normal suppression of the TSH response to TRH following T3.

Adult↗
PubMed1992

Neuroendocrine effects of intravenous clomipramine in depressed patients and healthy subjects.

OBJECTIVE: Neuroendocrine challenge paradigms have been used to asses serotonergic systems in depression, but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in depressed patients and matched control subjects. METHODS: Thirty hospitalized patients who met DSM-III-R criteria for major depression, and 30 healthy control subjects who were matched for age, sex, and season of year for the time of study, received 12.5 mg of intravenously administered clomipramine. RESULTS: The depressed patients demonstrated significant blunting of prolactin responses to clomipramine, as well as trends toward blunted ACTH and cortisol responses. There was no difference between the patient and control groups in growth hormone responses, plasma clomipramine levels, or self-reports of side effects. CONCLUSIONS: These data support the hypothesis that depressed patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine. Further study is required to delineate the mechanisms responsible for the abnormal response to intravenously administered clomipramine in depression.

Adolescent↗
PubMed1991

Oxytocin selectively increases holding and licking of neonates in preweanling but not postweanling juvenile rats.

Preweanling rats exhibit components of maternal behavior (MB) after brief periods of contact with neonates; the latency of onset of MB rises considerably after weaning. Oxytocin (OXT) stimulates MB in adult rats. The effects of intracisternal (IC) administration of OXT (2 micrograms) on pup-directed and other behaviors in preweanling and postweanling juvenile rats were tested. Compared with saline and no treatment, OXT significantly increased active holding of pups in preweanling but not postweanling juvenile rats. No other components of adultlike MB were stimulated by OXT. OXT also decreased inactive touching of pups and robustly increased selfgrooming in juveniles at all ages tested. It is concluded that OXT facilitation of active pup-holding and licking in preweanling rats may be an extension of OXT-induced self-grooming to pups and may also be related to OXT activation of MB in adult rats.

Age Factors↗
PubMed1991

Behavioral and endocrine interactions between thyrotropin-releasing hormone and ethanol in normal human subjects.

Thyrotropin-releasing hormone (TRH) has been shown to antagonize the depressant effects of ethanol in animals, but conflicting findings have been reported in humans. To test whether TRH counteracts any of a variety of ethanol-sensitive behavioral measures in normal human subjects and for an effect of ethanol on TRH-induced thyrotropin (TSH) and prolactin (PRL) response, we administered TRH (500 micrograms) or placebo over 1 min intravenously, 30 min after subjects had ingested 0.8 g/kg of ethanol or a placebo drink. Blood samples for TSH and PRL were drawn prior to and 15 and 30 min after injection. Eight male subjects were studied in a balanced, crossover design with each subject receiving placebo-placebo, TRH-placebo, placebo-ethanol, and TRH-ethanol. Whereas ethanol had significant and expected effects on subjective measures, memory, disinhibition, reaction time and time perception, TRH failed to counteract any ethanol effect, except for a small effect in one memory task. Similarly, no effect of ethanol on TRH-induced TSH or PRL response was found. Though the behavioral findings could be interpreted to indicate that TRH does not alter ethanol sensitive behaviors in humans it will be necessary to utilize higher dosages of TRH and/or TRH analogues before firmly drawing this conclusion.

Adult↗
PubMed1991

Dose-response studies with thyrotropin-releasing hormone (TRH) in abstinent male alcoholics: evidence for selective thyrotroph dysfunction?

A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) has been reported in subjects with a history of alcoholism whereas prolactin (PRL) responses have generally been normal. One hypothesis proposed to explain the reduced TSH response is down-regulation of pituitary TRH receptors. If this is correct, PRL response should also be diminished. To account for the different dose-response characteristics of TSH/PRL we have given four dosages of TRH (25, 100, 500 and 800 micrograms) to eight noncirrhotic, male alcoholics abstinent from ethanol a minimum of 28 days and to seven male control subjects. Across the TRH dose range the alcoholic subjects exhibited reduced basal TSH (p = .01) and a reduced TSH response (p = .0023) but no differences in basal and stimulated PRL levels. Alcoholic subjects had higher basal T4, T3 and FT4I values than did control subjects but covarying for T4, T3 and FT4I did not change the significance of either TSH or PRL findings. No significant differences in estradiol, estrone, testosterone, cortisol or glucose were noted between groups. The present study confirms the observation of a lower TSH response to TRH in abstinent alcoholics and indicates that the lower response cannot be overcome by increasing TRH dosage. The similar PRL response between groups suggests normal lactotroph function in noncirrhotic abstinent alcoholics and argues against the pituitary TRH receptor down-regulation hypothesis.

Adult↗
PubMed1991

The effects of thyroid hormones on potassium-stimulated release of 3H-GABA by synaptosomes of rat cerebral cortex.

Depolarization-induced release of neurotransmitters from nerve endings is triggered by the rapid entry of Ca through voltage-sensitive channels. Low (1 to 10 nmol/L) concentrations of L-triiodothyronine (T3), but not D-T3, reverse T3 (rT3) or L-thyroxine (T4), enhance fast-phase depolarization-induced 45Ca uptake by rat brain synaptosomes. In the present study the effects of thyroid hormones on the release of 3H-gamma-aminobutyric acid (3H-GABA) by cerebral cortical synaptosomes from adult male Sprague-Dawley rats were determined by a superfusion technique. It was found that low (1 to 10 nmol/L) concentrations of T3, but not D-T3, rT3, or T4, significantly enhanced Ca-dependent 3H-GABA release by synaptosomes exposed to a high K depolarization buffer for 5 sec. Low concentrations of T3 did not enhance basal 3H-GABA release or release produced by exposure to depolarization buffer for 30 seconds. Much higher concentrations (10 mumol/L) of both T3 and T4, but not rT3, D-T3, or D-T4, stimulated 3H-GABA release produced by exposure to depolarization buffer for 30 seconds.

Animals↗
PubMed1990

Depolarization-dependent 45Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine.

Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain.

Animals↗
PubMed1989

Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients.

High-affinity and saturable membrane-bound dopamine binding sites have been characterized in rat and human gastrointestinal tissues. Although their role in experimental ulcerogenesis has been suggested, dopamine receptor activity in peptic ulcer disease has not been investigated. Radioligand binding studies were performed with mucosal tissue homogenates obtained from the antrum and duodenum of six male healthy volunteers and six male duodenal ulcer patients. The binding assay was performed in triplicate with a crude membrane fraction using [3H]dopamine as a ligand at a final concentration of 1 nM at 22 degrees C in the dark. Nonspecific binding (which usually comprised about 30% of total binding) was determined in the presence of a 100-fold excess of unlabeled dopamine. A significant (P less than 0.05) increase of [3H]dopamine binding was found in duodenal mucosa of duodenal ulcer patients. [3H]Dopamine binding in stomach (antrum) of normal and duodenal ulcer patients did not differ significantly. These findings provide preliminary evidence for a role of dopamine receptors in duodenal ulcer and suggest that biochemical abnormalities of gut dopamine function may be operative in the pathogenesis of peptic ulcer disease.

Binding Sites↗
PubMed1988

Influence of thyroid states on stress gastric ulcer formation.

Thyroid hormones exert a critical developmental and regulatory role on the morphology and biochemistry of gastrointestinal mucosal cells. However, the relationship between thyroid function and stress gastric lesion formation remains undetermined. This study was designed to test the hypothesis that thyroid states may affect the acute development of gastric lesions induced by cold-restraint stress. Normal (euthyroid), hyperthyroid (200 micrograms of T4 i.p. x 7 days) and hypothyroid (thyroidectomized) rats were used. Gastric lesion incidence and severity was significantly (p less than 0.05) increased in hypothyroid rats, whereas in contrast hyperthyroid rats developed significantly less gastric lesions. As anticipated, plasma levels of thyroxin (T4) were significantly (p less than 0.01) elevated in hyperthyroid rats, and undetectable in hypothyroid rats. Acute pretreatment with i.p. cimetidine (100 mg/Kg), but not T4 (200 micrograms/Kg) 1 h prior to stress completely prevented gastric lesions formation in hypothyroid rats. Finally, binding of 3H-dihydroalprenolol to beta-adrenergic receptors on brain membranes prepared from frontal cortex was reduced by 20% in hypothyroid rats after 3 h of stress. These and other data contained herein suggest that thyroid hormones contribute to modulate the responsiveness of the gastric mucosa to stress. The increased rate of ulcerogenesis observed in hypothyroid rats appears to be mediated by gastric acid secretion. The central mechanism of this response may involve decreased brain nonadrenergic receptor function.

Animals↗