Steroid hormone action

See also Hormone Hierarchy of Action, Steroid Hormones, Steroid Hormone Synthesis... 

Figure 10.1 Mechanism of Steroid hormone action. Steroid hormones (S) penetrate plasma membranes and bind to cytoplasmic receptors (R). The steroid-receptor complex enters the nucleus and binds to DNA, stimulating transcription and translation of specific genes.

The area of nonsteroidal antiestrogens along with other classes of nonsteroidal antagonists of sex-steroid hormone action has been reviewed to 1986, and these compounds have been grouped by chemical stmcture as a basis of classification rather than any biochemical or biological test system utilized to assess antagonist activity (46). 

Steroid Hormones and Neurosteroids. Steroids (qv) can affect neuroendocrine function, stress responses, and behavioral sexual dimorphism (78,79) (see Steroids). Mineralocorticoid, glucocorticoid, androgen, estrogen, and progesterone receptors are localized in the brain and spinal cord. In addition to genomic actions, the neurosteroid can act more acutely to modulate the actions of other receptors or ion channels (80). Pregnenolone [145-13-17, ( ) dehydroepiandosterone [53-43-0] C H2 02 (319) are excitatory neurosteroids found in rat brain, independent of adrenal... 

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

VITAMIN Be IS IMPORTANT IN AMINO ACID GLYCOGEN METABOLISM IN STEROID HORMONE ACTION... 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

Although clinical deficiency disease is rare, there is evidence that a significant proportion of the population have marginal vitamin Bg status. Moderate deficiency results in abnormalities of tryptophan and methionine metabolism. Increased sensitivity to steroid hormone action may be important in the development of hormone-dependent cancer of the breast, uterus, and prostate, and vitamin Bg status may affect the prognosis. 

Volume XXXVI. Hormone Action (Part A Steroid Hormones)... 

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

None of these findings undermines the importance of the intracellular genomic actions of steroids. Rather, they increase the richness of the cellular actions of steroid hormones and raise the possibility that there may be connections between genomic and nongenomic actions of steroids. For example, genomic action may induce receptors that mediate nongenomic effects. Moreover, the activation of oxytocin receptors by progesterone is dependent... 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

Fig. 1.1. General mechanism of action of steroid hormones. Steroid hormones cross through the plasmatic membrane without apparent difficulty favored by gradient. Some, which can be considered prohormones, are metabolized and transformed into more active products. This is the case with testosterone, which becomes dihydrotestosterone (DHT) in the target tissues of androgens, through the 5-alfa-reductase enzyme. The hormone binds to the receptor, a soluble protein of the cellular cytosol that, in the absence of hormone, is found associated with other proteins (hsp90 and others) that maintain the receptor in an inactive state. The hormone-receptor bond causes the other proteins to separate and a homodimer to be formed. The homodimer is the activated form of the receptor since it is capable of recognizing the genes that depend on that steroid hormone as well as of activating its expression, which leads to the synthesis of specific proteins...

The entrance of steroid hormones into the cells has always been assumed to be a passive phenomenon, based on its solubility in the phospholipids of the cell membrane. Nevertheless, the existence of specific fixation of steroid hormones to cell membranes has opened the possibility of their entrance into the cells mediated by proteins of the membrane (Levin 2002). Nevertheless, it has not been possible to verify that they participate in some way in the transportation of steroids to the interior of the cell (Beato et al. 1996 Beato 1989). For them, other possible extragenomic actions have been postulated such as enzymes that participate in the metabolism of hormones or even membrane receptors (Beato et al. 1996 Chirino et al. 1991 Fernandez et al. 1994 Gruber et al. 2002 Revelli et al. 1998). 

Steroid hormones regulate a very extensive assembly of functions in numerous corporal tissues. Estrogens, the steroid hormones to which the majority of this chapter is dedicated, regulate from basic functions related to reproduction, the development of the skeleton, the maintenance of arterial tension, or diverse nervous functions. The molecular studies on the mechanism of action of estrogens have set the foundations that will permit us to understand how they carry out such diverse functions in such dissimilar tissues as well as how some substances that act through the estrogen signaling pathway can exercise opposite functions in different tissues. In this respect, there are five facts of particular importance that constitute the central nucleus of this revision ... 

Brann DW, Hendry LH, Mahesh V (1995) Emerging diversities in the mechanism of action of steroid hormones. J Steroid Biochem Mol Biol 52 2... 

Revelli A, Massobrio M, Tesarik J (1998) Nongenomic actions of steroid hormones in reproductive tissues. Endocr Rev 19 3... 

Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling M (2000) Multiple actions of steroid hormones-a focus on rapid, nongenomic effects. Pharmacol Rev 52 513-556... 

Conneely OM (2001) Perspective female steroid hormone action. Endocrinology 142 2194-2199... 

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