Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the epidermis following application of three corticosteroids, betamethasone 17-valerate, hydrocortisone 17-butyrate, and hydrocortisone have been studied histometrically in human volunteers. The reduction in epidermal thickness observed correlated significantly with a reduction in size of the viable epidermal cells. There was no significant reduction in the number of cells constituting the viable epidermis. These findings indicate that thinning of the epidermis is a function of cell size rather than cell number. The epidermal changes developed quickly and were rapidly reversible. It is suggested that measurement of cell size may be an early and sensitive index of atrophogenicity induced by topical corticosteroids. 0.1% Hydrocortisone 17-butyrate and 0.1% betamethasone 17-valerate showed equivalent potency in causing epidermal thinning and reduction in cell size. Reduction in cell size paralleled increasing concentrations of betamethasone 17-valerate, indicating a positive dose-effect relationship.
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PMID:Corticosteroid effect on epidermal cell size. 67 51

Corticosteroid-induced dermal atrophy has been studied in the rat using daily application of ethanolic solutions to small areas of flank skin. After 12 days of treatment, the degree of atrophy was determined by comparing the weights of skin plugs (16 mm diameter) taken from the treated areas with contralaterally paired control areas. Doses can be adjusted so that systemic effects are minimized and only local effects are observed. Hydrocortisone, hydrocortisone butyrate, dexamethasone, betamethasone, desonide and triamcinolone acetonide all produce atrophy in the rat, and the degree of thinning is dose dependent. Potencies in the dermal atrophy assay compare directly with topical anti-inflammatory potencies in the rat, and the presence of fluorine in the steroid molecule is not a determining factor in the production of atrophy.
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PMID:Corticosteroid-induced dermal atrophy in the rat. 90 45

Hydrocortisone administered systemically for 3 weeks has no effect on any phase of epidermal cell proliferation as measured by autoradiographic methods. However, the speed of cell differentiation (maturation) is increased, resulting in a thinning of the living epidermis due to the shorter epidermal cell life. Comparison of the epidermis from two body sites (ear and sole of foot) in mice receiving 2.4 mug per gm body weight per day of hydrocortisone in drinking water for 3 weeks revealed no change in the labeling with [3H]thymidine, the mitotic indices, or the lengths of the cell cycle phases. Quantitation of the epidermal cell compartments showed that thinning of the epidermis with hydrocortisone was due to the loss of an identical number of differentiating epidermal cells per unit surface from both body sites. In both sites there was the same increased rate of maturation of postmitotic cells while the proliferative cell-pool remained unresponsive to the hormone. The alteration of the speed of cell maturation is the principal action of hydrocortisone in epidermis. The results indicate that the epidermal cellular concentration of, and the susceptibility to, the hormone were identical in ear and sole of foot despite the differing speeds of turnover of the two tissues.
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PMID:Selective action of hydrocortisone on postmitotic epidermal cells in vivo. 127 Aug 32

The hairless mouse has been used as a model to distinguish between local and systemic atrophogenic effects of topical steroids. Hydrocortisone-17-butyrate, betamethasone-17-valerate, budesonide and clobetasol-17-propionate were applied topically daily for 21 days. Skinfold thickness and dermal DNA synthesis of treated and untreated skin were evaluated as parameters of local and systemic atrophogenicity. Further, body weight gain and thymus weight were assessed as markers of systemic activity. With respect to local effects, skin thickness and dermal DNA synthesis both proved to be good parameters. Of the systemic parameters, thymic involution and body weight gain paralleled quite well the skin thinning on the untreated side. The results confirmed the potency differences of the steroids. Furthermore, they emphasize the usefulness of the hairless mouse to assess the relative safety with respect to local and systemic side effects of chronically applied topical corticosteroids.
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PMID:The hairless mouse as a model for study of local and systemic atrophogenic effects following topical application of corticosteroids. 167 10

We comprehensively characterized the effects of a unique natural gain-of-function mutation in the glucocorticoid receptor (GR), GRAla610Val, in domestic pigs to expand current knowledge of the phenotypic consequences of GR hypersensitivity. Cortisol levels were consistently reduced in one-week-old piglets, at weaning and in peripubertal age, probably due to a reduced adrenal capacity to produce glucocorticoids (GC), which was indicated by an adrenocortical thinning in GRAla610Val carriers. Adrenocorticotrophic hormone (ACTH) levels were significantly reduced in one-week-old piglets only. Expression analyses in peripubertal age revealed significant downregulation of hypothalamic expression of CRH and AVP, the latter only in females, and upregulation of hepatic expression of SERPINA6, by GRAla610Val Transcriptional repression of proinflammatory genes in peripheral blood mononuclear cells (PBMCs) from GRAla610Val carriers was more sensitive to dexamethasone treatment ex vivo However, no significant effects on growth, body composition, blood chemistry or cell counts were observed under baseline conditions. These results suggest that GRAla610Val-induced GR hypersensitivity elicits a compensatory reduction in endogenous, bioactive glucocorticoid levels via readjustment of the hypothalamus-pituitary-adrenal (HPA) axis early in ontogeny to maintain an adequate response, but carriers are more sensitive to exogenous GC. Therefore, GRAla610Val pigs represent a valuable animal model to explore GR-mediated mechanisms of HPA axis regulation and responses to glucocorticoid-based drugs.
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PMID:A naturally hypersensitive glucocorticoid receptor elicits a compensatory reduction of hypothalamus-pituitary-adrenal axis activity early in ontogeny. 2744 Apr 22