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Cited by 83Hormonal and reproductive studiesEstrogen and related hormone effectsProstate Cancer Treatment and Research

Demonstration of partial characterization of cytosol receptors for testosterone

Gustafsson, Jan A., Pousette, Ake·1975·Biochemistry
DOI 10.1021/bi00685a009
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Abstract

Androgen uptake was investigated in several peripheral organs after administration of (1,2,6,7 minus -3H)testosterone to castrated male rats. The animals were killed after 30 min, the organs were taken out, and the radioactivity was determined after tissue combustion. A relatively high accumulation of androgen was found in pancreas, adrenals, spleen, thigh muscle, kidneys, and liver in addition to the classical androgen target organs coagulation glands, seminal vesicles, prostate, preputial glands, and harderian glands. In a second serier of experiments, nuclear and cytosol fractions were prepared from prostate, seminal vesicles, coagulation glands, preputial glands, spleen, submaxillary glands, kidneys, and pancreas from castrated male rats give (1,2,6,7 minus -3H)testosterone, and these fractions were then characterized by thin-layer and radio-gas chromatography with respect to their patterns of labeled steroids. Only prostate and seminal vesicles were found to contain significant amounts of nuclear 5alpha-(-3H)dihydrotestosterone. The major nuclear androgen was (-3H)testosterone that was the only detectable labeled steroid in coagulation glands, preputial glands, and spleen and that constituted 70% or more of the nuclear radioactivity in seminal vesicles, submaxillary glands, kidneys, and pancreas. These results indicate that testosterone itself may be the predominant active androgen principle in vivo in most androgen target organs and that conversion to 5alpha-dihydrotestosterone is generally not a prerequisite for androgen activity. Using an ultrasensitive micromodification of isoelectric focusing (cf. M. Katsumata and A. S. Goldman (1974), Biochem. Biophys. Acta 359, 112. It was possible to show that cytosol from kidney; submaxillary gland, thigh muscle, and levator ani muscle and nuclei from kidney and submaxillary gland contained androgen-binding proteins with pI's in the region 4.6-5.1 ("4.6 minus 5.1 Complex"). This complex also formed in vitro after incubation of (1,2,6,7 minus -3H)testosterone with cytosol from kidney and submaxillary gland. (1,2,6,7 minus -3H)Testosterone was bound with high affinity to receptor proteins in cytosol from both kidney, submaxillary gland, and thigh muscle with dissociation constants of 5.0 x 10 minus -12 M (kidney), 3.3 x 10 mi;nus -11 M and 4.1 x 10 minus -10 M (two types of binding sites, submaxillary gland), 2.4 x 10 minus -12 M (thigh muscle) and 1.9 x 10 minus -12 M (levator ani muscle). The number of binding sites was in all cases between 1 and 20 fmol/mg of protein. On the basis of these results the hypothesis is presented that a common class of testosterone receptors is present in most organs and that these receptors can be detected both in vivo and in vitro provided methods sensitive enough are utilized.

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  • Testosterone has been shown to induce its effects through binding to intracellular androgen receptors (ARs), which then regulate gene transcription.

    “Testosterone has been shown to induce its effects through binding to intracellular androgen receptors (ARs) (34), which then regulate gene transcription (18, 81).”

    From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [34]

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Authors
Gustafsson, J. A., & Pousette, A.
Affiliations
Houston Methodist (US)
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
1975-07-15
Volume
14
Issue
14
Pages
3094-3101
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
DOI
10.1021/bi00685a009
OpenAlex
W2085160329
Cited by
83
References
20
Citations by year
2023: 1 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 1
FWCI
8.01
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Keywords
testosterone, androgen receptor, dihydrotestosterone, androgen-binding protein, isoelectric focusing, castration, prostate, seminal vesicle, kidney, submandibular gland, thigh muscle, steroid binding affinity, androgen metabolism, castrated male rats
MeSH terms
Animals, Binding Sites, Binding, Competitive, Castration, Cell Nucleus, Chromatography, Gas, Cytosol, Kidney, Kinetics, Male, Muscles, Organ Specificity, Protein Binding, Proteins, Receptors, Cell Surface, Subcellular Fractions, Submandibular Gland, Testis, Testosterone, Time Factors, Rats

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