Steroid hormones antagonists

TABLE I Clinical uses of steroid hormone antagonists ... 

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). 

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. 

Classical or conventional pharmaceutical agents in combination with lactide/glycolide polymers have been widely studied since about 1973. In general, these compounds are bioactive agents usually produced by synthetic chemistry, with molecular weights of less than a few hundred and relatively stable structures. Examples include steroid hormones, antibiotics, narcotic antagonists, anticancer agents, and anesthetics. 

Aldosterone (183) is one of the key steroid hormones involved in regulation of the body s mineral and fluid balance. Excess levels of this steroid quickly lead to marked retention of sodium chloride, water and, often as a consequence, hypertension. The aldosterone antagonist spironolactone (184) has proven of great clinical value in blocking the effects... 

Several criteria determine whether a steroid-hormone-binding site is a putative receptor. First, the steroid-hormone-binding site must be present in hormone-responsive tissues or brain regions, and absent from nonresponsive ones. Second, it should bind steroids that are either active agonists or effective antagonists of the hormone effect, and should not bind steroids that are inactive in either sense. 

Because neuropeptides are active in very small amounts within the CNS they are more difficult to manipulate and study than steroid hormones. In addition, at present there is no simple method for administering neuropeptides within the CNS. (In animals, it is necessary to inject chemicals or their antagonists directly into the CNS, which is not feasible in humans.) Thus, most research on the behavioral effects of either oxytocin or vasopressin in humans is correlational, and subsequently difficult to interpret. However, animal studies also support the hypotheses described here (Carter, 1992 Uvnas-Moberg, 1996). 

The role of the steroid hormone receptors has extensively been defined with the help of natural and synthetic agonists and antagonists and with characterisation of transgenic and knock-out mice. In experimental studies, both approaches have been useful tools for validating that a physiological process is indeed mediated by the steroid hormone receptor imder investigation. 

Hormone Antagonists - Blockade of Steroid Hormone Receptors... 

Sexual receptivity. The effects of THC on sexual behavior in female rats and its influence on steroid hormone receptors and neurotransmitters in the facilitation of sexual receptivity was examined. Results revealed that the facilitatory effect of THC was inhibited by antagonists to both progesterone and dopamine D(l) receptors. To test further the idea that progesterone receptors (PR) and/or dopamine receptors (D[1]R) in the hypothalamus were required for THC-facilitated sexual behavior in rodents, antisense, and sense oligonucleotides to PR and D(1)R were administered intra-cerebroventricularly into the third cerebral ventricle of ovariectomized, estradiol benzoate-primed rats. Progesterone- and THC-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides to PR or to D(1)R. Antagonists to... 

Majewska MD, Schwartz RD Pregnenolone-sulfate an endogenous antagonist of the y-aminobutyric acid receptor complex in brain Brain Res 404 355-360, 1987 Majewska MD, Harrison NL, Schwartz RD, et al Steroid hormone metabolites are barbiturate-hke modulators of the GABAa receptor. Science 232 1004-1007, 1986... 

STEROID HORMONES STRUCTURE AND CONFORMATION OF AGONISTS AND ANTAGONISTS... 

Therapeutic advantages resulting from new chemical entities with improved receptor selectivity were mentioned earlier in this chapter and are described in detail in later chapters. Such drugs include a- and B-selective adrenoceptor agonists and antagonists, Hi and H2 antihistamines, nicotinic and muscarinic blocking agents, and receptor-selective steroid hormones. All... 

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