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Query: UMLS:C0338671 (Steroids)
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The specific androgen receptors for testosterone (T) (1) and 5alpha-dihydrotestosterone (DHT) in the cytosol fraction of the hypothalamus, preoptic area and brain cortex of the rat have been characterized using electrophoresis and isoelectric focusing in polyacrylamide gels. After labeling of the cytosol fractions in vivo and in vitro we were able to demonstrate androgen-receptor complexes moving with an electrophoretic mobility (R(f) of 0.5 in 3.25% acrylamide gels containing 0.5% agarose and 10% glycerol. Polyacrylamide gel electrophoresis was used as a quantitative assay for androgen receptors in the tissues. The hypothalamus, preoptic area and brain cortex were found to possess a single class of high affinity binding sites for androgens and the dissociation constants (K(D) were estimated to be 3.4, 4.3 and 2.6 X 10 (-10M) respectively. The binding capacities were 3.7 (hypothalamus), 3.5 (preoptic area) and 1.8 X 10 (-15) (brain cortex) moles of high affinity binding sites per mg protein. Like other androgen-receptor complexes, the testosterone-receptor complexes of the hypothalamus, preoptic area and brain cortex were temperature labile, sulfhydryl dependent and revealed a very slow rate of dissociation at o degrees C (t1/2 greater than 36 hr). The receptors in all the tissues had an isoelectric point of 5.8. The steroid specificity of the cytoplasmic androgen receptors was tested in vitro by the competing efficiency of different unlabeled steroids for (3H)-testosterone binding. In the three tissues in investigation the following order of affinity was found: DHT greater than T greater than Cyproterone acetate greater than progesterone greater than androstenedione greater than 17beta-estradiol. Cortisol did not effect androgen binding significantly. Thus, the physiochemical characteristics of the cytoplasmic androgen receptors of the hypothalamus, preoptic area and brain cortex are very similar, if not identical, to those of the androgen receptors described in the anterior pituitary, ventral prostate, epididymis and testis.
Steroids 1976 Feb
PMID:Characterization of the androgen receptors in the hypothalamus, preoptic area and brain cortex of the rat. 17 67

The effects of estradiol-17 beta on androgen uptake, metabolism and binding were studied in rat epididymis in vivo in comparison with cyproterone acetate. Steroids (250 ug/100 g body weight) were injected 5 min prior to 3H-testosterone in castrate rats. Estradiol-17 beta inhibited 3H-testosterone uptake into epididymal cytosol by 58% as compared to 38% by cyproterone acetate. 3H-Testosterone uptake into epididymal nuclei was inhibited 95% by estradiol-17 beta and 83% by cyproterone acetate. Total bound radioactivity in cytosol fractions was reduced to a greater extent by estradiol-17 beta than cyproterone acetate when either 3H-testosterone or 3H-dihydrotestosterone was injected. Binding of 3H-dihydrotestosterone to nuclear receptors was completely abolished by estradiol-17 beta; whereas approximately 20% binding remained in the nuclear extract after cyproterone acetate treatment. Metabolism of 3H-testosterone in vivo was also altered by estradiol-17 beta, resulting in diminished conversion to 3H-dihydrotestosterone. Cyproterone acetate, on the other hand, did not affect 3H-testosterone metabolism. Estradiol-17 beta and cyproterone acetate inhibited in vitro binding of 3H-dihydrotestosterone to the intracellular cytoplasmic receptor, but not the intraluminal androgen binding protein (ABP). These data suggest that estradiol-17 beta may have a more potent antiandrogenic effect on the epididymis than cyproterone acetate due to inhibition of 5 alpha reduction of testosterone as well as binding to the androgen receptor.
Steroids 1981 Mar
PMID:Estradiol-17 beta inhibition of androgen uptake, metabolism and binding in epididymis of adult male rats in vivo: a comparison with cyproterone acetate. 645 38

A novel computational technology derived from gene structure has been developed for screening, selecting, and designing pharmaceutical candidates. Pharmacophores, or three-dimensional molecular blueprints, were created by docking known active structures into specific sites in partially unwound DNA. The pharmacophores are composites of the van der Waals surfaces and hydrogen bonding functional groups of active molecules. Once created, molecules can be inserted into the pharmacophores and degree of fit quantitated by the volume of the molecule that fits within the composite surface and the magnitude of electrostatic interactions with charged atoms on the pharmacophore. Here, we describe endocrine pharmacophores and in particular the estrogen pharmacophore derived by docking active ligands into partially unwound DNA. Fit of candidate structures into the estrogen pharmacophore correlated with estrogenic (uterotropic) activity. For example, the super active estrogens moxestrol and 11beta-acetoxyestradiol fit better within the site than estradiol. Bisphenol A, a putative endocrine disrupter with suspected estrogenic activity, was a poor fit in the pharmacophore. Consistent with this prediction, bisphenol A was recently shown to lack uterotropic activity. The capacity of the endocrine pharmacophores to predict certain nontarget activities was demonstrated by using the antiandrogen cyproterone acetate that did not fit the estrogen or thyroid pharmacophores but fit partially into the progestin and glucocorticoid pharmacophores. Cyproterone acetate has been reported to have weak progestational and glucocorticoid activities. The pharmacophores provide for the first time a multidimensional computational method that can simultaneously predict multiple activities of diverse molecular structures.
Steroids 1999 Sep
PMID:Multidimensional screening and design of pharmaceuticals by using endocrine pharmacophores. 1050 11