Glucocorticoid steroid treatment

Two currently used steroids (clobetasone butyrate and betamethasone valerate) reproducibly cause vasoconstriction on topical application to human forearm skin. Progesterone, deoxycorticosterone, testosterone, and estradiol, even at 100- to 200-fold higher concentrations, cause no vasoconstriction when applied alone. Applied with clobestasone butyrate, testosterone and estradiol are without antagonist effect; in contrast, both progesterone and deoxycorticosterone antagonize the vasoconstrictor response in a dose-related fashion, with a half-maximal effect at 20-30 times the concentration of clobetasone. Neither progesterone nor deoxycorticosterone affects the vasoconstriction produced by the intradermal injection of epinephrine. In most glucocorticoid-responsive systems, progesterone and deoxycorticosterone are glucocorticoid antagonists, and estradiol and testosterone are inactive. We interpret these studies as evidence that the vasoconstrictor effects of topical steroids are mediated by occupancy of classical glucocorticoid receptors, rather than by nonspecific pharmacological mechanisms.

Sacks et al. (2005) reported the case of a 72-year-old man, described as professionally successful, intelligent, and cultivated, with polymyalgia rheumatica, who after being treated with prednisone developed a psychosis and dementia , which several behavioral neurology and neuropsychiatry consultants initially diagnosed as early dementia or Alzheimer's disease . [12] Large dosage variations in the patient's medication (including a self-increased dosage from 10 mg/day to as much as 100 mg/day for at least 3 months) produced extreme behavioral changes, from missed appointments to physical altercations, and eventually admission to a psychiatric ward and later to a locked Alzheimer facility. During this time, neuropsychological testing showed a decline in the patient's previously superior IQ as well as deficits in memory, language, fluency, and visuospatial function, which given the patient's age was considered to be compatible with early dementia. When the steroid treatment ended after a year, the patent's confusion and disorganized appearance stopped immediately. Within several weeks, testing showed strong improvement in almost all cognitive functions. His doctors were surprised at the improvement, since the results were inconsistent with a diagnosis of dementia or Alzheimer's. Testing after 14 months showed a large jump in Full Scale IQ from 87 to 124, but mild dysfunction in executive function, memory, attentional control, and verbal/nonverbal memory remained. [12]

Levels of HDAC2 mRNA, but not other histone deacetylases, were significantly decreased in bronchoalveolar lavage cells but not in peripheral blood mononuclear cells from steroid-resistant patients with asthma. Overexpression of glucocorticoid receptor β in cells selectively reduced HDAC2 mRNA and protein levels. Silencing of glucocorticoid receptor β in bronchoalveolar lavage cells from patients with asthma significantly increased HDAC2 mRNA. Luciferase activity assays with HDAC2 promoter reporter constructs identified two glucocorticoid-inducible regions in the HDAC2 promoter. Promoter activity was increased more than fourfold in dexamethasone-treated cells cotransfected with glucocorticoid receptor α. Cotransfection of glucocorticoid receptor β abolished this effect in a dose-dependent manner.

Glucocorticoid steroid treatment

glucocorticoid steroid treatment


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