Non-genomic effects of corticosteroids

In a healthy, vitamin D–replete, elderly population (70–90 y of age), no correlation was found between serum 1,25(OH)D 3 concentration and knee-extension strength, although both declined with age ( 61 ). This finding was the same in the study by Grady et al ( 62 ), in which 98 healthy, mostly vitamin D–replete, volunteers (>69 y of age) showed no significant differences in knee extension or flexion strength after treatment with μg 1,25(OH)D 3 /d or a placebo for 6 mo. Although muscle strength declined by %/y in this population, serum 1,25(OH)D 3 concentrations remained stable with age, increasing only moderately after 6 mo of treatment.

Calcium metabolism appears to underlie neuronal cell death via excitotoxicity, [103] [104] [105] [106] and hormonally active vitamin D confers a protective effect in vitro at physiologically relevant concentrations up to 100nM but not above. [107] This mechanism of protection appears to be mediated via a downregulation of L-type voltage-sensitive Ca 2+ ion channels, [107] an effect which has also been seen in bone cells. [108] [109] These L-type channels have been implicated in excitotoxicity. [110] [111]

Eplerenone is an antimineralocorticoid , or an antagonist of the mineralocorticoid receptor (MR). [14] Eplerenone is also known chemically as 9,11α-epoxy-7α-methoxycarbonyl-3-oxo-17α-pregn-4-ene-21,17-carbolactone and "was derived from spironolactone by the introduction of a 9α,11α-epoxy bridge and by substitution of the 17α-thoacetyl group of spironolactone with a carbomethoxy group". [10] The drug controls high blood pressure by blocking the binding of aldosterone to the mineralocorticoid receptor (MR) in epithelial tissues, such as the kidney. [3] Blocking the action of aldosterone decreases blood volume and lowers blood pressure. [6] It has 10- to 20-fold lower affinity for the MR relative to spironolactone , [14] and is less potent in vivo as an antimineralocorticoid. [3] However, in contrast to spironolactone, eplerenone has little affinity for the androgen , progesterone , and glucocorticoid receptors . [14] [3] It also has more consistently observed non-genomic antimineralocorticoid effects relative to spironolactone (see membrane mineralocorticoid receptor ). [3] Eplerenone differs from spironolactone in its extensive metabolism, with a short half-life and inactive metabolites. [3]

Non-genomic effects of corticosteroids

non-genomic effects of corticosteroids


non-genomic effects of corticosteroidsnon-genomic effects of corticosteroidsnon-genomic effects of corticosteroidsnon-genomic effects of corticosteroidsnon-genomic effects of corticosteroids