Specific, Nongenomic Actions of Steroid Hormones

Abstract

Traditionally, steroid hormone action has been described as the modulation of nuclear transcription, thus triggering genomic events that are responsible for physiological effects. Despite early observations of rapid steroid effects that were incompatible with this theory, nongenomic steroid action has been widely recognized only recently. Evidence for these rapid effects is available for steroids of all clones and for a multitude of species and tissues. Examples of nongenomic steroid action include rapid aldosterone effects in lymphocytes and vascular smooth muscle cells, vitamin D3 effects in epithelial cells, progesterone action in human sperm, neurosteroid effects on neuronal function, and vascular effects of estrogens. Mechanisms of action are being studied with regard to signal perception and transduction, and researchers have developed a patchy sketch of a membrane receptor-second messenger cascade similar to those involved in catecholamine and peptide hormone action. Many of these effects appear to involve phospholipase C, phosphoinositide turnover, intracellular pH and calcium, protein kinase C, and tyrosine kinases. The physiological and pathophysiological relevance of these effects is unclear, but rapid steroid effects on cardiovascular, central nervous, and reproductive functions may occur in vivo. The cloning of the cDNA for the first membrane receptor for steroids should be achieved in the near future, and the physiological and clinical relevance of these rapid steroid effects can then be established.

Nongenomic stimulation of vacuolar H + -ATPases in intercalated renal tubule cells by aldosterone

“…Several nongenomic effects of aldosterone have been described (17,(37)(38)(39). These involve rapid modulations of epithelial Na and K channel activity and of Na͞H exchange (40,41).…”

Management of hypotension and low systemic blood flow in the very low birth weight neonate during the first postnatal week

“…In addition, corticosteroids inhibit prostacyclin production and the induction of nitric oxide synthase, 37 and thus limit the pathological vasodilation associated with the nonspecific or specific inflammatory response of the critically ill neonate. In addition to these genomic effects, corticosteroids exert certain nongenomic actions, 38 resulting in a rapid increase in the sensitivity of the cardiovascular system to catecholamines. 33,38 Relative adrenal insufficiency, especially in the VLBW neonate, is the other factor contributing both to the increased incidence of vasopressor resistance and the enhanced responsiveness to hydrocortisone in this patient population.…”

“…In addition to these genomic effects, corticosteroids exert certain nongenomic actions, 38 resulting in a rapid increase in the sensitivity of the cardiovascular system to catecholamines. 33,38 Relative adrenal insufficiency, especially in the VLBW neonate, is the other factor contributing both to the increased incidence of vasopressor resistance and the enhanced responsiveness to hydrocortisone in this patient population. 34 In the VLBW neonate, relative adrenal insufficiency is thought to contribute to the disruption of the balance between adrenergic receptor destruction and synthesis, resulting in decreased sensitivity of the cardiovascular system to endogenous and exogenous catecholamines.…”

Sex-dependent effects of gonadal steroids and cortisol on cardiac contractility in rainbow trout

“…However, there is a decrease in stress-induced C levels in both sexes during spawning compared with non-reproductive periods (Donaldson and Fagerlund, 1968;Pottinger et al, 1995). Similar to the sex steroids, positive inotropic actions of glucocorticoids have been demonstrated in cardiac tissue of mammals (Yano et al, 1994;Wehling, 1997;Falkenstein et al, 2000) and amphibians (Hajdu and Szent-Györgyi, 1952). Thus, we felt that it was also important to determine whether C serves as a potential modulator of cardiac function in fishes.…”