Androgen Receptors in Mouse Kidney: A Study of Male, Female and Androgen-Insensitive (tfm/y) Mice<sup>1</sup>

Bullock, Leslie P.; Bardin, C. Wayne

doi:10.1210/endo-94-3-746

Cited by 156 publications

(38 citation statements)

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“…The extensive metabolism by baboon cytosol of 5a-dihydrotestosterone to relatively inactive androgens in the absence of significant metabolism of testosterone is similar to that reported for rat heart cytosol (Krieg et al, 1978) and mouse kidney cytosol (Bullock and Bardin, 1974) and appears to be characteristic of some tissues in which testosterone does not serve as prehormone. [Testosterone typically is the prehormone in male accessory organs of reproduction (c.f.…”

Section: Discussionsupporting

confidence: 68%

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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Section: Discussionsupporting

confidence: 68%

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

Lin

McGill

Shain

1981

Circulation Research

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“…In isotonic homogenates of normal cells dihydrotestosterone binding is principally in the 8S region of the gradient, whereas in high molarity buffers the major binding peak is in the 4-4.5S region. Thus, the cultured human fibroblast has an approximate 8S dihydrotestosterone-binding protein similar to the one characterized in other androgen target tissues such as rat prostate (16,17), rat preputial gland (18), mouse kidney (19)(20)(21), and mouse submandibular gland (22).…”

Section: Resultsmentioning

confidence: 91%

Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.

Griffin¹,

Punyashthiti

Wilson³

1976

J. Clin. Invest.

230

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“…24, see Participant Discussion), although we find low androgen binding with these animals. Bullock and Bardin (20), who studied presumed androgen receptor in mouse kidney extracts, also found proteins with high affinity for both testosterone and dihydrotestosterone, with apparent higher affinity for testosterone; this androgen binding was absent in Tfm/Y kidney cytosol. Their data also suggest a binding protein with affinity for testosterone, dihydrotestosterone, and estradiol, since they reported that testosterone binding was completely blocked by estradiol at only 100-fold above the testosterone concentration.…”

Section: Methodsmentioning

confidence: 91%

Androgen- and estrogen-binding macromolecules in developing mouse brain: biochemical and genetic evidence.

Fox¹

1975

Proc. Natl. Acad. Sci. U.S.A.

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Androgen-and estrogen-binding macromolecules from the hypothalamus plus preoptic area of 3-to 4-week-old mice have been detected and partially characterized. These components bind the respective hormones with high affinity (saturating at 4-8 nM) and sediment with rates typical of presumed steroid receptors (4.0-4.5 S in 0.15 M NaCl, 5.0-7.5 S without salt). A 90-95% reduction in androgen binding found in the androgen-insensitivity mutant mouse, testicular feminization (Tfm), provides a genetic control for the specificity of binding. This reduced androgen binding with Tfm/Y mutants and blocking experiments with non-radioactive estradiol [estra-1,3,5(10)triene-3,17f-diolj and testosterone (17#-hydroxy-4-androsten-3-one) indicate the existence of at least two binding components: one with high affinity only for estradiol, the other with affinity for both androgens and estrogen. Based on these properties, a receptor mechanism that detects relative concentrations of androgens and estrogens is proposed. Steroid hormones influence the development of the mammalian brain prior to their participation in the regulation of adult brain functions and behavior (1-3). Testosterone (17#-hydroxy-4-androsten-3-one) or estradiol [estra-1,3,5(10)-triene-3, 17#3-diol] administered to neonatal female rats or mice can permanently prevent the cyclic release of gonadotropins that is characteristic of the estrous cycle. These steroids presumably affect differentiation of brain tissues (4) which affect production of factors that modulate pituitary gonadotropin release. Thus, testosterone or estradiol administered to female rats or mice during the first week after birth sterilizes them by causing them to have acyclic rather than cyclic gonadotropin patterns as adults.The mechanism by which testosterone affects the brain is unclear. Some reports indicate specific androgen binding proteins in rat hypothalamus (5-8), whereas others have challenged the specificity of the androgen binding by these presumed receptors (9, 10). In light of this uncertainty, a second mechanism was hypothesized. The ability of estradiol to produce "neonatal masculinization" (11, 12) similar to, but not identical to, that induced by testosterone, and the capacity for rat brain tissues to convert androgen to estrogen (13-15), support the suggestion that the effects of androgens on brain are mediated by the estradiol receptor (16). This mechanism does not require an androgen receptor, only that testosterone be converted to estradiol and then bind to an estrogen receptor.To compare androgen and estrogen binding we have examined brain tissues from normal mice and from an androgen-insensitive mutant mouse used as a negative control. We have previously detected, partially purified, and examined estradiol-binding macromolecules of hypothalamus plus preoptic area from pre-pubertal (17) and neonatal (18) mice. We now report a second class of binding macromolecules with high affinity for testosterone and dihydrotestosterone.* The data provide evidence that these androgen...

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Androgen Receptors in Mouse Kidney: A Study of Male, Female and Androgen-Insensitive (tfm/y) Mice¹

Cited by 156 publications

References 0 publications

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

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

Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.

Androgen- and estrogen-binding macromolecules in developing mouse brain: biochemical and genetic evidence.

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Androgen Receptors in Mouse Kidney: A Study of Male, Female and Androgen-Insensitive (tfm/y) Mice1

Cited by 156 publications

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

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

Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.

Androgen- and estrogen-binding macromolecules in developing mouse brain: biochemical and genetic evidence.

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Androgen Receptors in Mouse Kidney: A Study of Male, Female and Androgen-Insensitive (tfm/y) Mice¹