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Biomedical subjects

G G Gordon

Publications and source records attributed to G G Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1983

Potentiation of glucocorticoid activity by 5 beta-dihydrocortisol: its role in glaucoma.

5 beta-Dihydrocortisol potentiated the threshold level (the smallest dose producing a measurable effect) of topically applied cortisol (0.02 percent) and dexamethasone (0.003 percent) in causing nuclear translocation of the cytosolic glucocorticoid receptor in rabbit iris-ciliary body tissue. 5 beta-Dihydrocortisol accumulates in cells cultured from trabecular meshwork specimens from patients with primary open-angle glaucoma, but not in similar cells derived from nonglaucomatous patients. In view of the sensitivity of patients with primary open-angle glaucoma to the effects of glucocorticoids in raising intraocular pressure, this potentiation may be responsible for the steroid sensitivity and for the ocular hypertension seen in this disorder.

Animals↗
PubMed1983

Phenytoin effect on the proliferation of rat oral epithelium is mediated by a hormonal mechanism.

Systemic pretreatment of male rats with phenytoin (PHT) (30 mg/100 g body weight) significantly (P less than 0.001) increased mitotic frequency, shortened mitotic duration and renewal time in the basal cells of the oral epithelium. This effect of PHT was abolished by simultaneous s.c. injection of cyproterone acetate (CyA) (50 micrograms/100 g body weight) or by castration. CyA treatment of intact rats or castration further decreased mitotic frequency, prolonged mitotic duration and turnover time in the oral epithelium. The effect of castration was reversed by the simultaneous s.c. injection of testosterone propionate (Tp) (50 micrograms/100 g body weight). These results suggest that PHT effect on epithelial proliferation is mediated by a hormonal mechanism.

Animals↗
PubMed1983

Altered cortisol metabolism in cells cultured from trabecular meshwork specimens obtained from patients with primary open-angle glaucoma.

Cells cultured from trabecular meshwork specimens obtained from patients with primary open angle glaucoma (TMPOAG cells) exhibited two major differences in cortisol-metabolizing enzymes when compared with similar cells from nonglaucomatous patients. One is a marked increase (greater than 100-fold) in delta 4-reductase activity and the other is a decrease (4-fold) in 3-oxidoreductase activity. Peripheral lymphocytes from one of these patients as well as from five additional patients with POAG, did not show these abnormalities, indicating that the defects are not found in all cortisol-metabolizing cells. The abnormal metabolism of cortisol by TMPOAG cells may be of significance in the pathogenesis of POAG.

Adult↗
PubMed1983

The effect of dexamethasone on the in vitro incorporation of precursors of extracellular matrix components in the outflow pathway region of the rabbit eye.

The present study demonstrates that the cells of the outflow pathway region incorporate precursors of the extracellular matrix components during in vitro incubation. Addition of dexamethasone (10(-7) M) to the incubation mixture led to changes in precursor incorporation that were precursor and cell specific. The steroid significantly decreased the incorporation of 3H-glucosamine and increased the incorporation of 3H-proline in the outflow pathway cells and in the fibroblasts of the adjacent sclera. The specificity of the hormone effect was demonstrated by its inability to alter 3H-leucine incorporation. By contrast, in iridial fibroblasts dexamethasone caused a decreased incorporation of 3H-glucosamine while not affecting the incorporation of 3H-proline. Our results suggest that dexamethasone causes an increase in collagen synthesis in the target cells most closely related to the outflow pathway. Further, the decreased incorporation of 3H-glucosamine with dexamethasone suggests decreased synthesis of glycosaminoglycans, glycoproteins or possibly glycolipids in these same cells.

Animals↗
PubMed1982

Glucocorticoid receptor binding in bovine lens.

The present study demonstrates glucocorticoid receptor localization in the nuclei of cells of the anterior epithelium and bow region and its absence in all other regions of the lens. Both autoradiographic and biochemical studies show that triamcinolone acetonide is inactive whereas tetrahydrocortisol (previously considered to be an inactive metabolite of cortisol) is an active competitor of dexamethasone binding to the glucocorticoid receptor in the bovine lens. The consistency of these findings by both techniques supports the validity of this observation. In addition, it indicates that autoradiography can be used for studying glucocorticoid agonist/antagonist relationships in the human lens, where only small amounts of tissue are available.

Animals↗
PubMed1982

Characterization of a glucocorticoid receptor and the direct effect of dexamethasone on herpes simplex virus infection of rabbit corneal cells in culture.

Homogenates prepared from a previously established cell line derived from rabbit cornea contain a macromolecule with many properties of a glucocorticoid receptor, namely high affinity (KD = 6 x 10(-9)M) and saturable capacity (135 femtomoles/mg protein) for dexamethasone, extreme heat lability, and a pattern of competition similar to that found in other glucocorticoid target cells. Intact cells specifically bind dexamethasone with an affinity similar to that found in homogenates, and the amount of steroid bound at saturation is approximately 60,000 molecules of dexamethasone per cell. Specific dexamethasone binding was found to be localized to the cell nucleus. The corneal cells were susceptible to infection with herpes simplex virus (HSV). Dexamethasone increased cell susceptibility to the virus and facilitated the spread of the infection throughout the corneal cell culture. This effect was observed at concentrations of dexamethasone as low as 10(-9) M. Tetrahydrocortisol, an inactive glucocorticoid metabolite that does not compete with dexamethasone binding to the receptor, did not enhance HSV infection at a high concentration (10(-5) M). This study demonstrates a direct effect of dexamethasone on corneal cell-HSV interaction in the absence of exogenous immunologic factors. This effect of dexamethasone may be mediated by the glucocorticoid receptor.

Animals↗
PubMed1981

Effect of ethanol intake on cellular regulation of testosterone-5 alpha-reductase in rat oral tissues.

The effect of ethanol on testosterone-5 alpha-A-ring reductase activity was studied in the whole homogenate and/or subcellular fractions (microsomes and cytosol) of buccal mucosa, gingiva, liver and prostate from intact ethanol-fed (36% of dietary calories were given as ethanol for up to 360 days) and pair-fed control rats. An increased enzyme activity was found in the hepatic, prostatic and gingival homogenates from ethanol-fed rats. No difference in the enzyme activity was seen in the homogenates of buccal mucosa. However, when the buccal mucosal microsomal fraction was used a significant (P less than .005) increase in the enzyme activity was found in the ethanol-fed rats. It was determined that the lack of an increase in 5 alpha-reductase activity in the buccal mucosal homogenates from ethanol-fed rats was due to the presence of a cytosolic inhibitor of this enzyme. Enzyme kinetics showed a decrease in the velocity in correlation with the increasing concentration of cytosolic inhibitor (Vmax control = 1.9 and Vmax ethanol = 1.7, 1.45 and 1.0 nmol, respectively). The apparent Km (0) and Kp (1--3) values were similar for all combinations (4.5 x 10(-5) M). In addition, a similar Ki constant (2.2 mg of cytosolic protein) was found for different testosterone concentrations. These results suggest that the ethanol-induced cytosolic inhibitor in buccal mucosa combines with the enzyme, independent of the substrate and inhibits it by an allosteric mechanism. Studies using dialysis, heating and tryptic digestion suggests that the inhibitor is a protein.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1981

Corneal-conjunctival uptake of topical 3H-dexamethasone in the rabbit eye.

Topically administered 3H-dexamethasone was localized radioautographically to the nuclei of several cell types in the cornea and conjunctiva. In the cornea, label was found in the epithelium and keratocytes. In the conjunctiva, label was found in the epithelium and in the connective tissue cells and blood vessel endothelial cells of the stroma. Prior administration of a 350-fold excess of nonlabeled hormone completely suppressed this localization, indicating that these cells are specific glucocorticoid target cells. There was no localization found in the corneal endothelium. Accumulation of silver grains between corneal stroma and Descemet's membrane suggests that this membrane acts as a partial barrier to diffusion of the steroid.

Animals↗
PubMed1980

Effect of chronic alcohol ingestion on the biosynthesis of steroids in rat testicular homogenate in vitro.

The activity and kinetics of delta 5-3 beta-dehydrogenase and 17 alpha-hydroxylase, using labeled pregnenolone as substrate, were measured in gonadal homogenates from rats fed alcohol or isocalorically substituted carbohydrate for 40 days. There was no difference in the rate or reaction kinetics for either enzyme noted between control and alcohol-treated animals when the assays were carried out in the presence of saturating amounts of exogenous pyridine nucleotide cofactors. However, when exogenous cofactors were omitted from the reaction mixture, there was decreased activity of the delta 5-3 beta-dehydrogenase system and increased activity of the 17 alpha-hydroxylase reaction. Furthermore, a cofactor-specific inhibiting effect on delta 5-3 beta-dehydrogenase activity by NADH and NADPH was found. Incubation of gonadal homogenates from the alcohol-treated animals with pyruvate on lactate (in the absence of exogenous cofactors) resulted in an increase and a decrease, respectively, in enzyme activity. These studies indicate that chronic alcohol use decreases gonadal delta 5-3 beta-dehydrogenase activity and that this is most likely due to an effect of the agent on the concentration and/or availability of pyridine nucleotide cofactors rather than to a direct effect on the enzyme. This phenomenon may account for the mechanism by which alcohol decreases testosterone secretion in these animals.

Animals↗
PubMed1980

Changes in testosterone levels in the rat following intraperitoneal cocaine HCl.

Independent groups of mature rats were administered IP injections of either 15 mg cocaine HCl or normal saline. Animals were lightly anesthetized after 45', 90', 120', or 180' and blood plasma assayed for testosterone by RIA. Experimental subjects showed increasing levels until the longest delay value when a substanial drop was noted. The importance of this finding is noted, both with regard to the issue of drug abuse as well as a potential confounding element in the analysis of chemical kindling experiments.

Animals↗
PubMed1980

Glucocorticoid localization by radioautography in the rabbit eye following systemic administration of 3H-dexamethasone.

Dexamethasone was localized radioautographically in the nuclei of target cells of the rabbit eye following intravenous administration of the labeled steroid. Specifically bound steroid was found in the nuclei of stromal and endothelial cells of the outflow pathway region. This suggests that the glucocorticoid-induced alteration in outflow facility may be mediated by specific effects in these target cells. Nuclear localization was also found in conjunctiva, iridial smooth muscle, choroidal stroma, retina, and sclera, suggesting a physiologic role for glucocorticoids in these tissues as well.

Animals↗
PubMed1979

The effect of alcohol ingestion on hepatic aromatase activity and plasma steroid hormones in the rat.

Chronic alcohol ingestion in the rat resulted in increased hepatic aromatase activity, elevation of plasma estradiol, and a decrease in plasma testosterone levels. Testicular incubation studies indicated that the source of the estrogen was not of gonadal origin but was, most likely, due to increased peripheral conversion. The failure of HCG in vitro to restore testicular secretion of testosterone to normal levels suggested a direct action of alcohol, or a metabolic product, on gonadal secretory processes, as distinct from trophic hormone effects. This study demonstrates that many of the hormonal alterations seen in cirrhosis of the liver in man may be produced directly by alcohol feeding without cirrhotic changes in the rat.

Aging↗