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Biomedical subjects

G S Roth

Publications and source records attributed to G S Roth.

At least 217 records · Page 12Linked to original sources

Reductions in glucocorticoid inhibition of glucose oxidation and presumptive glucocorticoid receptor content in rat adipocytes during aging.

Exposure of adipocytes to glucocorticoid hormones in vitro causes inhibition of glucose transport and metabolsim. Maximal inhibition of glucose oxidations is reduced from 42-50 to 22-25 to 5-8% in young, mature, and senescent rat adipocytes, respectively. Percent values also reflect absolute reductions since basal levels of glucose oxidation per cell are constant at all ages. Adipocytes of CD strain rats continue to increase in size throughout their lifespan, while cell size remains constant during the latter 80% of the Wistar adipocyte lifespan. Thus, cellular age, as well as possibly size, seems to be associated with these changes since they occur in adipocytes of both strains. Concentrations as well as absolute numbers of presumptive glucocorticoid receptors per cell are progressively reduced during maturation and aging of adipocytes in both rat strains. Glucocorticoid effects are known to require about 2 h and can be blocked by various antimetabolites during this period, reminiscent of classical steroid receptor-mediated responses. Thus, gradual loss of glucocorticoid receptors from adipocytes during maturation and aging may be related to progressively decreased glucocorticoid responsiveness.

Adipose Tissue↗

Reduced glucocorticoid responsiveness and receptor concentration in splenic leukocytes of senescent rats.

Glucocorticoids are 63% less effective in inhibiting [5-3-h] uridine uptake by splenic leukocytes of senescent rats (24-14 months) than by those of mature adult animals (12-14 months). Scatchard analyses reveal 57% fewer specific glucocorticoid binding sites in cytosols of the senescent group. Reduced binding of cortisol by cytosol macromolecules of intact viable leukocytes at 37 degrees C is also apparent in the older rats. Specific binding of glucocorticoids to cytoplasmic macromolecules appears to be closely linked, if not required, for inhibition of [5-3-hi1 uridine uptake. This is evidenced by the fact that both inhibition and specific binding are simultaneously blocked by progesterone administration. In addition, the amount of specific binding as well as the degree of inhibition of [5-3-h] uridine uptake is concentration dependent up to 2. 10-6 M cortisol. Thus, decreased glucocorticoid reponsiveness in the cells from senescent rats appears to be due primarily to decreased concentrations of specific glucocorticoid receptors.

Adrenal Glands↗

Balanced macromolecular biosynthesis in "protoplasts" of Streptococcus faecalis.

Osmotically fragile forms of Streptococcus faecalis 9790 were grown in 0.5 m sucrose- or 0.5 m NH(4)Cl-stabilized medium. The "protoplast" cultures exhibit an average growth rate constant of 0.66 to 0.94 mass doublings/hr. In a variety of experiments, turbidity and the net content of protein, ribonucleic acid (RNA) and deoxyribonucleic acid increase at the same rate, indicating balanced macromolecular biosynthesis. A total of two to three mass doublings was obtained, with no evidence of cell division. After osmotic shock, "protoplast" cultures released 93 to 94% of their RNA content in a form not sedimentable at 12,800 x g for 15 min, in contrast to streptococci, which released 7% of their RNA content after the same treatment.

Ammonium Chloride↗

Incorporation of radioactive macromolecular precursors into intact cells and osmotically stabilized "protoplasts" of Streptococcus faecalis.

Growing "protoplasts" of Streptococcus faecalis were shown to incorporate newly administered radioactive precursors in the same manner as growing intact streptococci. No observable differences could be found between the size of the leucine precursor pools of the two cultures. The extent of turnover of protein and ribonucleic acid in both "protoplast" and streptococcal cultures appeared to be identical. Finally, the absolute rate of macromolecular biosynthesis was found to be equivalent whether determined on the basis of "new" or "old" label incorporation.

Bacterial Proteins↗

Impaired estrogen stimulation of RNA polymerase II activity in uterine nuclei of senescent rats.

The effects of age on estrogen stimulated nuclear RNA polymerase II activity were studied in uteri of ovariectomized mature (6-8 months) and senescent (24 months) rats. Basal levels of RNA polymerase II activity were the same in both age groups. Following 17 beta-estradiol (E2) administration, RNA polymerase II activities increased at 6 h and reached a peak at 12 h in mature rats. In old rats, however, activities did not change until 12 h and reached a maximum at 18 h after injection. The effects of various E2 doses were examined at 6 h after injection. In mature rats, 1 microgram of E2 per 100 g body weight stimulated polymerase II activity, and maximum response was observed above 3 micrograms per 100 g. In senescent rats, this activity did not increase at doses below 3 micrograms per 100 g, but was stimulated by 10 micrograms of E2 per 100 g body weight to levels similar to those in mature rats. These results indicate that induction of uterine nuclear RNA polymerase II activity is delayed and less sensitive to E2 in old female rats than in their young counterparts.

Aging↗

Reduction of motor behavioral deficits in senescent animals via chronic prolactin administration. I. Rotational behavior.

The effects of chronic prolactin administration on amphetamine or dopamine (DA) induced rotational behavior was examined in mature (6 month) and senescent (24 month) Wistar rats which were unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine. Prolactin (150 ng/hr) was administered for 7 days via subcutaneously implanted Alzet minipumps. Amphetamine (AMPH) (0, 10 micrograms) or DA (0, 25 micrograms) was administered through cannula which had been implanted into the right (intact) striatum. Both DA-active agents were given prior to pump implantation and on day 4 of prolactin administration. The AMPH was dissolved in saline (1 microliter; pH, 5.5-6.0), while DA was dissolved in N2 bubbled distilled H2O (1 microliter; pH, 5.5-6.0) and the animals were pretreated with nialamide (50 mg/kg) intraperitoneally 1 hr before DA or DA-vehicle injection. The order of drug administration was counterbalanced within the age groups. Results showed that both groups of animals exhibited higher rotational behavior scores following prolactin treatment. In fact, there was a trend toward greater enhancement of rotational behavior in the senescent animals following prolactin treatment than that seen in mature animals. These results parallel those reported previously wherein it was found that striatal DA receptor concentrations (as assessed with [3H]spiperone binding) were higher in prolactin treated mature and senescent animals than in their respective controls. The findings suggest that there is a relationship between increases in the density of striatal DA receptors and improvement in motor performance tasks in senescent animals.

Aging↗

Effect of aging on striatal dopamine receptor subtypes in Wistar rats.

Both D1 and D2 dopamine receptor subtypes are lost from striata as Wistar rats age. The magnitude of loss differs slightly for the two subtypes (approximately 30% for D1, approximately 40% for D2) as does the temporal pattern (progressive loss from 3 to 24 months for D2, no decrease in D1 after 12 months) although most D2 loss also occurs in the first half of the lifespan. Dopamine stimulated adenylate cyclase activity also declines during striatal aging in a manner roughly proportioned to D1 receptor loss.

Adenylyl Cyclases↗

Muscarinic acetylcholine receptor subtype mRNA expression and ligand binding in the aged rat forebrain.

Previous studies indicate that a 20-30% decline in muscarinic acetylcholine receptor binding occurs in localized areas of rat brain during aging. In this study, reduced [3H]-quinuclidinyl benzilate binding was observed in striata from 24-25-month-old rats relative to 5-6-month-old animals using homogenate binding assays. To determine if the decline in receptor concentration occurs as a result of decreased receptor synthesis, the expression of the m1, m3, and m4 muscarinic receptor mRNAs as well as [3H]-QNB binding were determined in adjacent sections of young and old male rats using in situ hybridization and in vitro receptor autoradiography respectively. A significant decline in collective muscarinic receptor binding as assessed by [3H]-QNB was observed in the caudate putamen, olfactory tubercle, nucleus accumbens, and several frontal and parietal cortical areas. The only difference observed in muscarinic mRNA expression for any of the three subtypes examined was a decline in m1 hybridization in the olfactory tubercle. The results of this study demonstrate that the regional brain areas displaying age-related decreases in receptor binding do not correlate with those areas showing a decrease in muscarinic receptor expression. Apparently, the decline in muscarinic acetylcholine receptor density with age does not result from a decline in receptor gene expression.

Aging↗

Muscarinic receptor concentrations and dopamine release in aged rat striata.

The extent to which age-related decreases in muscarinic enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from perifused striatal slices is dependent upon the loss of striatal muscarinic receptors (mAChR) was determined. Both K(+)-ERDA and mAChR (M1, M2) concentrations were assessed from the same animals (3, 5-7 and 24-27 months). Results indicated associated decreases of 70% in oxotremorine-enhanced K(+)-ERDA and 36% in Bmax (3H-QNB) (3 and 24-27 months groups). Decrease of mAChR Bmax was not the result of membrane sequestration. Although both the concentrations of M1 and M2 muscarinic receptor subtypes decline with age, only the M2 receptor decline was correlated with the age-related decreases in muscarinic enhancement of K(+)-ERDA (r = .71, p less than 0.001). Results suggest that age-related decreases in mAChR concentrations as being partially responsible for deficits in muscarinic enhancement of K(+)-evoked release of DA.

Aging↗