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Biomedical subjects

G S Roth

Publications and source records attributed to G S Roth.

At least 199 records · Page 11Linked to original sources

Effects of age on control of lipolysis during fasting.

Loss of body weight, girth, epididymal fat pad weight, and adipocyte size were examined in male, virgin, Wistar rats aged 2, 6, 12 and 22-24 months during 5 days of fasting. Relative reductions in all four parameters were greatest in the 2-month-old animals, with little differences among the older three age groups. In contrast, absolute weight loss was greatest in 12, and 24-month-old rats. Body weights were also greatest in these two groups. Plasma epinephrine and norepinephrine increased to the same levels in all 4 groups during the fast. Similarly, insulin decreased to the same levels in all groups although the oldest rats already exhibited low levels prior to fasting. Thus, possible age differences in the lipolytic response to fasting do not appear due to age-related differences in important lipolytic (catecholamine) and antilipolytic (insulin) hormone levels. Possible age-related differences in lipolytic response to fasting may instead reflect changes in other hormones which regulate lipolysis, or an altered sensitivity of adipocytes to such hormones.

Aging↗

Decrease in rat uterine estrogen receptors during aging: physio- and immunochemical properties.

Rat uterine estrogen receptors decrease in concentration by about 45% between maturity (6-12 months) and senescence (22-24 months). No change in binding affinity occurs over this period. No age differences were observed in the thermostability, hormone-induced stability, or specificity of binding for various steroids. Most importantly, immunochemical titration of receptors with specific antiserum revealed that the ratio of immunoreactive to functional receptor is not changed with age. Thus, the apparent loss of rat uterine estrogen receptors during aging does not seem to be due to the appearance of a nonfunctional receptor population detectable by presently available immunoreagents.

Aging↗

In Vitro biosynthesis of adipocyte proteins having the characteristics of glucocorticoid receptors.

A quantitative method for the measurement of putative glucocorticoid receptor biosynthesis in rat adipocytes is described. The method utilizes the incorporation of radioactive amino acids into newly synthesized putative receptor proteins and their subsequent separation from other labeled proteins by affinity chromatography. Dexamethasone and deoxycorticosterone-Sepharose are used as affinity adsorbants. Specific binding of radioactive putative receptors to these gels is time- and protein concentration-dependent, and is abolished by exposure of cells to cycloheximide, pretreatment of adipocyte cytosol preparations with unlabeled steroids or incubation of cytosols at 37C for 4 h. Specifically bound radioactivity, which represents about 10% of the radioactivity initially associated with affinity adsorbants can be quantitatively eluted under rigidly defined conditions including high ionic strength. Specifically eluted material, which comprises up to 50% of total eluted radioactivity sediments at 3.8 S in sucrose gradients containing 1 M KCl, and electrophoretically migrates on 0.1% SDS gels in single band with a molecular weight of about 50 000. The sedimentation coefficient is comparable to that of the native adipocyte cytosol receptor not subject to affinity chromatography (3.7 S). Under low ionic-strength conditions most of the native receptor sediments at 8 S. The molecular weight of 50 000 is in the range of those reported for glucocorticoid receptors of liver (45 000---66 000 for monomers). The properties of the protein or proteins measured in the present system are therefore consistent with the current state of knowledge regarding glucocorticoid receptors in adipocytes.

Adipose Tissue↗

Age-related decrease in repair of oxidative damage to surface sulfhydryl groups on rat adipocytes.

Adipocytes were isolated from the Wistar and Sprague-Dawley strains of rats of different ages. An impermeable reagent, mercury-[3H] dextran, was used to quantitate the sulfhydryl groups on the surface of these cells. The application of this reagent after the pre-reduction of cells with 2-mercaptoethanol yielded a measure of the total sulfhydryl and disulfide groups located there. Aging was found to significantly decrease the ratio of the number of exofacial sulfhydryl groups to the total number of exofacial sulfhydryl and disulfide groups.

Adipose Tissue↗

Contractile and biochemical correlates of beta-adrenergic stimulation of the aged heart.

The age dependence of contractile and associated biochemical parameters of basal- and catecholamine-stimulated myocardial contractile performance was investigated using isolated perfused septa from adult and senescent rats. Base-line maximum rate of force development (dF/dt), beta-receptor number and affinity, cAMP levels, and cAMP-dependent protein kinase activity were not different in the two age groups. During maximal isoproterenol stimulation, the increase in dF/dt was 40% less in the senescent hearts, and the cAMP levels and cAMP activation of protein kinase increased two fold but to the same extent in both age groups. The maximum contractile response to dibutyryl cAMP (DBcAMP) in the senescent was half that observed in the adult hearts. However, adult and senescent septa responded equally to an increase in perfusate [Ca2+] to 1.0 mM, which enhanced contractility to the same extent as that obtained with isoproterenol and DBcAMP in adult septa. These data taken together suggest that the factors that limit the contractile response to catecholamines in the senescent heart act subsequent to protein kinase activation but proximal to the Ca2+-troponin interaction.

Adrenergic beta-Agonists↗

Hormone action during aging: alterations and mechanisms.

The ability to respond to certain hormones is altered during the aging process. Attempts to elucidate the mechanisms involved in such changes have focused primarily on the various molecular components which mediate hormone actions. These include chromatin, the nucleus, cytoplasmic factors, adenylate cyclase and hormone receptors. Age related changes have been observed at all of these levels, and in some cases have been correlated with changes in biological responsiveness to particular hormones. This review attempts to summarize the data obtained in these studies. Possible interpretations are discussed and future directions for such research are suggested.

Adenylyl Cyclases↗

Dissociation of glucocorticoid inhibition of glucose transport and metabolism by increase in adipocyte age and/or size.

Exposure of adipocytes from young rats (2--3 months old) to dexamethasone in vitro results in 40--50% inhibition of glucose transport and metabolism. Comparable experiments with older rats reveal that the hormonal effect on glucose metabolism is progressively reduced to about 20% in 12- to 13-month-old animals and about 5% in 24- to 26-month-old animals. However, no effect of dexamethasone on the glucose transport system can be detected in either of the older age groups when three different sugars are used to measure transport activity. The ability of dexamethasone to inhibit glucose phosphorylation seems to be closely related to inhibition of overall glucose oxidation in both young and old adipocytes. That the membrane may be generally more resistant to control of glucose transport is suggested by failure or reduced ability of insulin, vitamin K5, and hydrogen peroxide to stimulate this function in older cells.

Adipose Tissue↗

Hormone receptor changes during adulthood and senescence: significance for aging research.

Receptors for various hormones have been examined throughout the adult life span. In most of these studies receptor concentrations were found to decrease with increasing age, either during senescence or earlier in adulthood. In contrast, binding affinities did not change with age. Tissues and cells examined have included liver, brain, adipose tissue, skeletal muscle, prostate, fibroblasts, and lymphocytes. Receptors for steroids as well as membrane-active hormones such as insulin, glucagon, catecholamines, and prolactin were studied. Rats, mice, dogs, and humans have been employed. Changes in hormone receptor levels appear to constitute a common manifestation of the aging process, and offer interesting model systems in which to study the control of genetic expression during senescence.

Adenylyl Cyclases↗

Age-related changes in the nigrostriatum: a behavioral and biochemical analysis.

Rotational behavior was examined prior to (Exp. 1) and following unilateral lesions (Exp. 2) in the substantia nigra of young and old rats. Before lesioning no preferences for turning to the left or right were seen in either age group following graded doses of amphetamine. However, after radiofrequency lesions of the left substantia nigra both young and old rats turned predominantly to the left, and the ratio of left to right turns increased as a function of amphetamine dose. However, there were significant differences between young and old rats in the effect of amphetamine on rotational behavior, with old rats showing decided decrements in response strength. Direct dopaminergic stimulation under apomorphine or dopaminergic receptor blockade with haloperidol produced no such age related deficits. The results are discussed in terms of possible presynaptic alterations in dopaminergic functioning with aging.

Aging↗

Testosterone secretion in the rat in response to chorionic gonadotrophin: alterations with age.

It has been reported by others that both prevailing blood concentrations of testosterone and Leydig cell response to gonadotrophin (up to 1 h after injection) are reduced in the aged male rat. Although resting levels of plasma testosterone in our aged (24-26 months old) Sprague-Dawley rat are also depressed compared with young (3-4 months) or mature (12 months) animals of the same strain, subcutaneous injection with human chorionic gonadotrophin for 3 days restores secretory function, producing testosterone levels indistinguishable from those of similarly stimulated younger rats. In short term experiments, old rats did show a diminished testesterone secretory response to human chorionic gonadotrophin 1 h after a single intravenous injection, consistent with previous reports, but restoration of normal stimulated levels was observed by 2 h, and persisted up to 24 h. These findings differ from the demonstrated intrinsic testicular hyporesponsiveness to gonadotrophin of aged men, and probably represented a state of chronic understimulation of the aged rat Leydig cells, due to low prevailing levels of LH.

Aging↗

Reduced glucocorticoid binding site concentration in cortical neuronal perikarya from senescent rats.

Isolated neuronal perikarya from cerebral cortices of senescent (24-26-month-old) male rats exhibit a 55-65% reduction in the concentration of specific cytosol glucocorticoid binding sites when compared to mature counterparts (12-13 months). Neuronal preparations from the two age groups are essentially identical with respect to yield, protein content, physiochemical integrity and purity as judged by enrichment for free glycine and reduction in carbonic anhydrase specific activity (relative to unfractionated cortical cell suspensions). Adrenalectomy does not alter the number of glucocorticoid binding sites in either group, and age differences do not appear due to differential partitioning of sites between nucleus and cytoplasm. It is suggested that loss of receptors from the cortical neuron population represents a possible mechanism by which glucocorticoid responsiveness may be decreased during aging.

Adrenalectomy↗