Androgen receptor translocation from cytosol of rat heart muscle, bulbocavernosus/levator ani muscle and prostate into heart muscle nuclei

Krieg, Michael; Smith, Kenneth T.; Elvers, Barbara

doi:10.1016/0022-4731(80)90023-0

Cited by 21 publications

(7 citation statements)

References 34 publications

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“…All three receptors are present in the rat levator ani muscle as well (see Refs. [3][4][5][6][7][8][9][10][11][12][13][14][15], and the androgen receptor (AR) in this muscle can be translocated in vitro into isolated cardiac muscle cell nuclei (16). The physicochemical properties of these receptors are very similar to those of receptors in the classical target tissues.…”

mentioning

confidence: 99%

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin*

1984

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It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. 1 alpha-Methyl-5 alpha-dihydrotestosterone (1 alpha-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [ RBAs relative to that of MT: MT greater than 19-nortestosterone ( NorT ; nandrolone) greater than methenolone (17 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3-one) greater than testosterone (T) greater than 1 alpha-methyl-DHT]. In other cases, AR binding was weak (RBA values less than 0.05): stanozolol (17 alpha-methyl-5 alpha- androstano [3,2-c]pyrazol-17 beta-ol), methanedienone (17 beta-hydroxy-17 alpha-methyl-1,4-androstadien-3-one), and fluoxymesterolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one) and ethylestrenol (17 alpha-ethyl-4- estren -17 beta-ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5 alpha-androstane-3 alpha, 17 beta-diol and its 3 beta-isomer (3 alpha- and 3 beta-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (1 alpha-methyl-DHT much greater than DHT greater than T greater than 3 beta-adiol greater than 3 alpha-adiol = 17 alpha-methyl-T greater than methenolone greater than methanedienone greater than stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases.(ABSTRACT TRUNCATED AT 400 WORDS)

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confidence: 99%

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin*

1984

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“…Subsequently Krieg et al (1978) characterized a rat myocardial cytoplasmic androphile (androgen-binding component) which had the properties of an androgen receptor. More recently, Krieg et al (1980) demonstrated in vitro limited capacity binding of rat myocardial cytoplasmic androgen receptors to rat myocardial nuclei. Comparable characterization of putative rat myocardial estrogen receptors (Stumpf et al, 1977) has not been reported.…”

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confidence: 99%

Hormone receptors of the baboon cardiovascular system. Biochemical characterization of myocardial cytoplasmic androgen receptors.

Lin

McGill

Shain

1981

Circulation Research

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SUMMARY Using the synthetic androtfen R1881 (17/S-hydroxy-17a-methyl-estra-4,9,ll-trien-3-one) as probe, we identified cytoplasmic androgen receptors in baboon myocardium. The relative binding affinity of selected steroids for the androgen receptor was R1881, 100%; Sa-dihydrotestosterone, 32.8%; testosterone, 29.6%, progesterone, 7.2%; R5020, 1.0%; and estradiol-17/3, 5.8%. The androgen receptor migrated on low ionic strength linear sucrose density gradients as a macromolecule with a sedimentation coefficient of 8.5S. Saturation analysis performed at 2°C (available sites) showed that the androgen receptor content of baboon myocardial cytoplasmic extracts was 9.9 i 1.4 fmol/mg protein and that the dissociation constant for R1681 was 1.16 ± 0.30 run. These cytoplasmic androgen receptors are indicated to be physiologically functional by previous autoradiographic studies (McGill et aL, 1980;McGill and Sheridan, 1981) that showed localization of radloisotope In nuclei of myocardial fibers following injection of baboons with 5a-dihydrotestosterone.

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“…INC. et al, 19771, and later androgen receptors were demonstrated and characterized biochemically in rat myocardial cytosol (Krieg et al, 1978). The androgen-receptor complex was subsequently shown to bind to a nuclear pellet made from rat myocardium (Krieg et al, 1980). Our laboratory demonstrated the nuclear uptake and retention of 3H-dihydrotesterone (3H-DHT) andlor its metabolites in heart and blood vessels of the rhesus monkey (Macaca mulatta) and the baboon (Papio sp.)…”

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confidence: 83%

Heart contains receptors for dihydrotestosterone but not testosterone: Possible role in the sex differential in coronary heart disease

et al. 1989

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The sex differential in coronary heart disease is well documented but poorly understood. Previous studies have demonstrated receptors for dihydrotestosterone (DHT) in the myocardium and smooth muscle cells of arteries from a number of species. In this autoradiographic study, we further investigated and characterized the in vivo uptake and retention of the androgen binding in the male baboon. Adult castrated male baboons were injected with 1 micrograms/kg bw 3H-testosterone; 1 hr after the injection, the animals were rapidly exsanguinated while under anesthesia. The heart and arterial system were removed and processed for autoradiography. As a negative control, one animal received both 3H-testosterone and 100-fold unlabeled testosterone. For positive controls, the pituitary gland, prostate, seminal vesicles, and other tissues were also removed and processed for autoradiography. In contrast to our previous finding with 3H-DHT, no nuclear uptake and retention of 3H-steroid was found in any of the cells in either the heart or the arterial system. In the positive control tissues, pituitary gland, prostate, seminal vesicles, and others, a very distinct nuclear uptake and retention of 3H-steroid was observed, which was completely inhibited by the simultaneous injection of 100-fold unlabeled testosterone. In the binding study, Scatchard analysis of the cytosol prepared from a 17-year-old female baboon demonstrated levels of androgen receptor (as determined by the use of radiolabeled R1881) comparable to that found in young adults.(ABSTRACT TRUNCATED AT 250 WORDS)

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Androgen receptor translocation from cytosol of rat heart muscle, bulbocavernosus/levator ani muscle and prostate into heart muscle nuclei

Cited by 21 publications

References 34 publications

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin*

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin*

Hormone receptors of the baboon cardiovascular system. Biochemical characterization of myocardial cytoplasmic androgen receptors.

Heart contains receptors for dihydrotestosterone but not testosterone: Possible role in the sex differential in coronary heart disease

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