Mineralocorticoid activity of different steroids

Geriatric Use : Clinical studies of prednisolone sodium phosphate , USP, oral solution did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with prednisolone sodium phosphate has not identified differences in responses between the elderly and younger patients. However, the incidence of corticosteroid-induced side effects may be increased in geriatric patients and appear to be dose-related. Osteoporosis is the most frequently encountered complication , which occurs at a higher incidence rate in corticosteroid-treated geriatric patients as compared to younger populations and in age-matched controls. Losses of bone mineral density appear to be greatest early on in the course of treatment and may recover over time after steroid withdrawal or use of lower doses (., ≤5 mg/day). Prednisolone doses of mg/day or higher have been associated with an increased relative risk of both vertebral and nonvertebral fractures, even in the presence of higher bone density compared to patients with involutional osteoporosis.

The receptor is activated by mineralocorticoids such as aldosterone and its precursor deoxycorticosterone as well as glucocorticoids , like cortisol . In intact animals, the mineralocorticoid receptor is "protected" from glucocorticoids by co-localization of an enzyme, Corticosteroid 11-beta-dehydrogenase isozyme 2 (. 11β-hydroxysteroid dehydrogenase 2; 11β-HSD2), that converts cortisol to inactive cortisone. It also responds to some progestins . Spironolactone and eplerenone are steroidal MR antagonists of the spirolactone group.

In 2 unrelated patients, Ulick et al. (1979) described a disorder in the peripheral metabolism of cortisol, manifested by hypertension, hypokalemia, low plasma renin activity, and responsiveness to spironolactone. Aldosterone levels were subnormal. Although the features suggested primary mineralocorticoid excess, no overproduction of mineralocorticoid could be demonstrated. One of the patients, who had been reported by New et al. (1977), was a 3-year-old Zuni Indian girl with hypertension, hypokalemia, and decreased secretion of all known sodium-retaining corticosteroids. The second patient was a boy of Middle Eastern parentage who had a stroke with residual left hemiparesis at age 7, and was first found to be hypertensive at age 9 (blood pressure as high as 250/180 mm Hg). Other findings included growth retardation, grade III retinopathy, hypokalemia, and hyposthenuria. Biochemical studies indicated a decreased rate of conversion of active cortisol to cortisone, and the authors postulated a defect in 11-beta-hydroxy oxidation of cortisol. Ulick et al. (1979) suggested the term 'apparent mineralocorticoid excess.'

A large part of the answer is that, in aldosterone-responsive cells, cortisol is effectively destroyed, allowing aldosterone to bind its receptor without competition. Target cells for aldosterone express the enzyme 11-beta-hydroxysteroid dehydrogenase, which has no effect on aldosterone, but converts cortisol to cortisone, which has only a very weak affinity for the mineralocorticoid receptor. In essence, this enzyme "protects" the cell from cortisol and allows aldosterone to act appropriately. Some tissues (. hippocampus) express abundant mineralocorticoid receptors but not 11-beta HSD - they therefore do not show responses to aldosterone because aldosterone is not present in quantities sufficient to compete with cortisol.

Mineralocorticoid activity of different steroids

mineralocorticoid activity of different steroids

A large part of the answer is that, in aldosterone-responsive cells, cortisol is effectively destroyed, allowing aldosterone to bind its receptor without competition. Target cells for aldosterone express the enzyme 11-beta-hydroxysteroid dehydrogenase, which has no effect on aldosterone, but converts cortisol to cortisone, which has only a very weak affinity for the mineralocorticoid receptor. In essence, this enzyme "protects" the cell from cortisol and allows aldosterone to act appropriately. Some tissues (. hippocampus) express abundant mineralocorticoid receptors but not 11-beta HSD - they therefore do not show responses to aldosterone because aldosterone is not present in quantities sufficient to compete with cortisol.

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