Search PubMed⌕ Search

Biomedical subjects

G A Mason

Publications and source records attributed to G A Mason.

At least 37 records · Page 2Linked to original sources
PubMed1995

Thyrotropin and prolactin responses to thyrotropin-releasing hormone in young men at high or low risk for alcoholism.

A reduced thyrotropin (TSH) response to TSH-releasing hormone (TRH) has been reported in a portion of abstinent alcoholic men without evidence of cirrhosis of the liver. It is not known whether this neuroendocrine change is a precursor of alcoholism or a sequelae of heavy alcohol consumption. Three of four published studies have found evidence for differences in TRH-induced TSH response in subjects at high risk for alcoholism, based on family history, compared with subjects at low risk for alcoholism. To test further the hypothesis that the TRH-induced TSH response is a vulnerability marker for alcoholism, we tested 25 young men with an alcoholic father [family history-positive (FHP)] and matched them, on alcohol consumption, to 25 young men with no identified first- or second-degree relatives with alcoholism [family history-negative (FHN)]. FHP subjects were further categorized based on whether their father had shown signs of alcohol problems before age 25 years (FHP-Early, n = 10) or after age 24 years (FHP-Late, n = 12). FHP subjects did not differ from FHN subjects in their baseline levels of thyroid hormones, glucose, cortisol, or TSH. However, the distribution of TSH responses in the FHP subjects was skewed toward lower values, compared with FHN subjects (p = 0.12). Furthermore, FHP-Late subjects had lower TSH responses than FHN subjects (p = 0.02), whereas the TSH response of FHP-Early subjects was not different from FHN subjects. Prolactin responses to TRH were similar across all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Neonatal stress transiently alters the development of hippocampal oxytocin receptors.

The development of brain oxytocin (OXT) receptors was examined following the mild stress of daily, 20 min separations of infant rats from their mothers (repeated separation condition) or in undisturbed controls. Changes in OXT receptors were characterized in cell membrane preparations, using the OXT receptor ligand [125I]d(CH2)5[Tyr(Me)2Thr4Tyr-NH9(2)]-ornithine vasotocin ([125I]OTA), from rats at 4, 8, 14, 22 postnatal days of age or as adults. In the hippocampus of control animals, [125I]OTA binding was highest at day 4 or 8 and declined thereafter. Repeated separation decreased the Bmax of [125I]OTA binding in whole hippocampus at day 8, an effect that did not persist into adulthood. This effect was found to be confined to the rapidly proliferating, dorsal hippocampus. It has been suggested that brain OXT is involved in both affiliative/social and stress-related behaviors. While the specific function of OXT receptors in hippocampus is currently unknown, mild stress to the infant and the disruption of infant-mother contact transiently alters the normal development of this system.

Animals↗
PubMed1994

Dose-response studies with protirelin.

BACKGROUND: A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (protirelin [TRH]) has been found consistently in a portion of patients with major depression. One hypothesis to explain this observation is that pituitary TRH receptors are down-regulated in major depression. One prediction stemming from this hypothesis is that prolactin (PRL) as well as TSH responses to TRH should be attenuated. To adequately test the pattern of protirelin-induced TSH and PRL responses with a protirelin dose-response design is necessary. METHODS: Four doses of protirelin (25, 100, 500, and 800 micrograms) were infused in an ascending schedule at intervals of 3 to 7 days in patients with major depression and in control subjects. Seven women and six men with major depression were compared with age- and gender-matched controls (five women and seven men). The TSH and PRL responses were measured at regular intervals following each dose of protirelin. RESULTS: No significant group differences in baseline levels of thyroid hormones or cortisol were present. Depressed men exhibited significant reductions in both TSH and PRL responses to protirelin across all doses compared with control men. Depressed women exhibited significant reductions in TSH responses but not in PRL responses compared with control women. CONCLUSIONS: The findings that men with major depression exhibit reductions in both protirelin-induced TSH and PRL responses support the hypothesis that TRH receptors are downregulated in depression. The findings in women are less clear and may represent the greater variance in the protirelin-induced PRL responses found in women.

Adult↗
PubMed1994

Estrogen increases affinity of oxytocin receptors in the medial preoptic area-anterior hypothalamus.

Analysis of binding data from saturation experiments using a radiolabeled oxytocin antagonist ([125I]OTA) demonstrated an increase in binding affinity after treatment with 5 micrograms estradiol benzoate (EB) for 3 days in membrane fractions from the medial preoptic area-anterior hypothalamus (MPOA-AH) of ovariectomized (OVX) rats. Analysis of data from competition experiments revealed high- and low-affinity [125I]OTA binding sites in the MPOA-AH, the medial basal hypothalamus (MBH), and hippocampus of OVX controls. Three days of EB treatment reduced low-affinity binding sites in the MPOA-AH and MBH, but not in the hippocampus. Treatment of membrane fractions from the MPOA-AH of oil-treated OVX rats in vitro with 100 nM OT or with estrogen or progesterone conjugated to bovine serum albumin (E-BSA and P-BSA) also reduced low-affinity [125I]OTA binding sites but BSA alone did not.

Animals↗
PubMed1994

Testosterone and religiosity as predictors of sexual attitudes and activity among adolescent males: a biosocial model.

A biosocial model of the effects of early adolescent testosterone levels and religiosity on adolescent males' sexual attitudes and activity over a 3-year period was examined. Using panel data for approximately 100 boys who were 12.5/13.0 years old at study entry, significant additive effects of free testosterone and frequency of attendance at religious services were demonstrated on the transition to first intercourse and other aspects of sexual behaviour and attitudes. No interactive effects of the two predictors were found. Boys with higher free testosterone levels at study entry who never or infrequently attended religious services were the most sexually active and had the most permissive attitudes. Boys with lower free testosterone who attended services once a week or more were the least active and reported the least permissive attitudes. For some behaviours, differences between free testosterone/attendance groups increased over time, resulting in substantial behavioural differences by the final round of measurement 3 years later.

Adolescent↗
PubMed1994

Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas.

Oxytocin binding (Bmax) was found to be higher in the ventral tegmental area (VTA) and the medial preoptic area (MPOA) at midparturition compared with Pregnancy Days 15-17 or Postpartum Days 5-7 in rat dams. Pup retrieval and assuming a nursing posture over pups were blocked in parturient dams by infusions of an oxytocin antagonist into the VTA or MPOA and by infusions of a vasopressin (V1) antagonist into the MPOA. These results implicate oxytocin in the VTA and MPOA and vasopressin in the MPOA, as well as a parturition-associated rise in oxytocin binding in these sites in the postpartum activation of maternal behavior.

Animals↗
PubMed1994

The subchronic effects of the TRH analog TA-0910 and bromocriptine on alcohol preference in alcohol-preferring rats: development of tolerance and cross-tolerance.

In a previous study, we showed that a single injection of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduced alcohol intake in alcohol-preferring (P) rats and increased their water intake over a 24-hr period. In the present study, the effects of seven consecutive, once-daily injections of TA-0910 (0.75 mg/kg, ip) on alcohol preference were determined. P rats developed tolerance to the attenuating effects of TA-0910 on alcohol intake within 3-5 days. Following the development of tolerance to TA-0910, rats were injected with the dopamine agonist bromocriptine (0.5 mg/kg, sc). In the presence of tolerance to TA-0910, the attenuating effect of bromocriptine on alcohol intake was reduced. When rats were made tolerant to the attenuating effects of bromocriptine, they exhibited tolerance to the attenuating effects of TA-0910. These findings indicate that tolerance to the effects of TA-0910 on alcohol intake occurs and suggest dopamine involvement in the mechanism of action of TA-0910 in reducing alcohol intake in P rats.

Alcohol Drinking↗
PubMed1993

Altered prolactin response to clomipramine rechallenge in healthy subjects.

The effect of an initial challenge with the serotonin (5-HT) uptake inhibitor clomipramine (CMI) on subsequent rechallenge was studied in healthy men who served as volunteers. Carefully screened volunteers were assigned to one of three conditions: (1) CMI challenge followed 2 weeks later by CMI rechallenge; (2) placebo challenge followed 2 weeks later by CMI challenge; and (3) CMI challenge followed 4 weeks later by CMI rechallenge. We found significant blunting of the prolactin response to CMI rechallenge 2 weeks (Signed Rank = -12, p = 0.05), but not 4 weeks after an initial challenge. Placebo challenge did not effect CMI challenge 2 weeks later. These findings suggest that a single exposure to IV CMI may cause 5-HT receptor changes that are present 2, but not 4 weeks later. The ramifications of this finding with regard to the use of 5-HT challenge paradigms in a test-retest design are discussed.

Adolescent↗
PubMed1993

Effects of concurrent subchronic treatments with desmethylimipramine and propranolol on beta-adrenergic and serotonin2 receptors in rat brain.

The effects of seven consecutive daily injections of desmethylimipramine (DMI 20 mg/kg) and propranolol (PRO 10 mg/kg) on 3H-dihydroalprenolol (3H-DHA) and 3H-ketanserin (3H-KET) binding in rat brain were examined. Analyses of saturation binding data using the iterative, nonlinear curve-fitting program LIGAND revealed that PRO increased, while DMI reduced, 3H-DHA binding site density in cerebral cortex without altering receptor affinity, as previously reported. DMI reduced 3H-KET binding site density without changing affinity, and PRO produced the same effect. In cerebral cortex and probably in hippocampus and striatum, DMI and PRO administered together increased the density of 3H-DHA binding sites (beta-adrenergic receptors) and reduced their affinity. This combination of drugs reduced the density of 3H-KET binding sites (5-HT2 receptors) in cerebral cortex, but did not change their affinity. These findings indicate a need for additional studies on the interactions of DMI and PRO and related drugs because of implications for the treatment of depressed patients with cardiovascular disorders.

Animals↗
PubMed1993

Sexual activity decreases oxytocin receptor densities in the thymus.

Sexual interactions have multiple effects on oxytocin systems in the brain. In the present study we observed that allowing estrogen-progesterone treated ovariectomized rats to be mounted ten times by a male significantly decreased the density (beta max) of thymic oxytocin receptors. Animals were ovariectomized and after recovery injected once daily for three consecutive days with 0.5 microgram estradiol benzoate (EB) followed by an injection of 500 micrograms progesterone on the fourth day 4-5 hr before testing. They were either placed in a cage with a sexually-active male until mounted ten times (mounted) or were briefly placed in the cage and removed before being mounted (unmounted). Both groups were then killed and their thymuses aseptically removed. Computerized analysis of saturation binding data showed that the densities of oxytocin receptors from mounted animals were significantly (p < 0.02) lower than those of unmounted controls (beta max for unmounted animals = 8.45 +/- 0.84 fmol/mg protein; and for mounted rats = 5.5 +/- 0.33 fmol/mg protein; t6 = 3.23). The possibility is discussed that sexual activity reduces thymic oxytocin receptors which may alter immune responsiveness to sexually-transmitted diseases.

Animals↗
PubMed1993

Effects of thyroid state on preference for and sensitivity to ethanol in Fischer-344 rats.

1. It has been reported by several groups that thyroid status can alter ethanol preference in rats. However, results using different methods and different strains of rats have not been consistent. 2. In this study, thyroidectomy or T4 augmentation was used to produce hypothyroidism or hyperthyroidism, respectively, in adult male Fischer-344 rats. 3. Preference for weak solutions (4 or 5%) of ethanol or tap water and ethanol-induced sedation and hypothermia were compared in hypothyroid, hyperthyroid and euthyroid rats. 4. No significant differences in preference indices (the ratios of ethanol to total liquid consumed) among the three groups were observed; however, for ethanol to contribute a greater portion of total calories ingested by hypothyroid rats than by euthyroid or hyperthyroid rats. 5. The duration of sleep resulting from a single i.p. injection of 2.5 mg/kg ethanol was increased (by 34%) in hyperthyroid rats and decreased (by 16%) in hypothyroid rats compared to euthyroid controls. Only the effect of hyperthyroidism was significant at the 0.05 level. 6. Colonic temperatures differed with thyroid state (hyperthyroid > euthyroid > hypothyroid) but the decrease produced by ethanol did not differ by thyroid state. 7. Observed differences in ethanol-induced sedation are consistent with differences in brain TRH levels and effects on neurotransmitter systems associated with different thyroid states.

Alcohol Drinking↗
PubMed1993

L-triiodothyronine: is this peripheral hormone a central neurotransmitter?

L-triiodothyronine (T3) has previously been shown to enhance fast-phase, depolarization-induced 45Ca uptake and 3H-gamma-aminobutyric acid release by rat brain synaptosomes at low nanomolar concentrations comparable to those reported for whole brain. Nevertheless, the physiologic importance of these nonnuclear-mediated effects of T3 has remained uncertain, in part because specific mechanisms and the presence of T3 at presumptive sites of action have not been demonstrated. Isotopic studies showing that L-tetraiodothyronine (thyroxine T4) and T3 are concentrated in synaptosomes, and that T4 is deiodinated to T3 suggested that endogenous levels of T3 in nerve terminals are probably much higher than in other compartments of the brain. In the present study we confirmed that endogenous levels of T3 in nerve terminals are at least eightfold higher, and may be as much as 60-fold higher, than in whole brain. More importantly, we showed that both 125I-labeled T3 and endogenous T3, but not 125I-T4 or endogenous T4, are released from depolarized synaptosomes, primarily by a Ca(2+)-dependent process. This demonstrates a mechanism for raising the level of T3 within the synapse, where the hormone may interact with pre- and postsynaptic binding (or uptake) sites, and suggests that the peripheral hormone T3 may be a neurotransmitter.

Animals↗
PubMed1993

Subclinical hypothyroidism: a modifiable risk factor for depression?

The authors assessed the lifetime history of major depression in 16 subjects with subclinical hypothyroidism and 15 subjects whose thyroid function was completely normal. The lifetime frequency of depression was significantly higher in the subjects who met the criteria for subclinical hypothyroidism (56%) than in those who did not (20%), suggesting that subclinical hypothyroidism may lower the threshold for the occurrence of depression.

Adult↗