Increased levels of nuclear androgen receptors in hyperplastic prostate of aging men

Ji, Grimaldo; Aw, Meikle

doi:10.1016/0022-4731(84)90375-3

Cited by 8 publications

(9 citation statements)

References 13 publications

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“…Androgen receptors (AR), although intuitively implicated in prostatic dysfunction, have not yet been definitively involved as evidenced by disagreement concerning their relevance to prostate pathology [17,[20][21][22][23][24]45,46]. The necessity to assay AR within a reproducible framework has been emphasised [47], but achievement of such an ideal is hindered by nonuniform distribution of AR among areas of the same prostate [48], between different prostate tissue types [15][16][17]49301, and possibly among different subnuclear compartments [8,9,50,51].…”

Section: Discussionmentioning

confidence: 99%

Association states of androgen receptors in nuclei of human benign hypertrophic prostate

Kyprianou

Davies

1986

The Prostate

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Androgen receptors (AR) were quantified in nuclei purified from unfractionated benign hypertrophic prostate (bph) tissue and from separated epithelium and stroma from bph specimens. Both epithelial and stromal cell nuclei contained AR, although concentrations in epithelial cell nuclei were higher and more variable. Variations in AR levels in epithelial cell nuclei reflected variations in unfractionated-tissue nuclei. Nuclear AR were further characterized regarding extractability with or resistance to 0.6 mol/lKCl and micrococcal nuclease. Nuclei from unfractionated tissue, epithelium, and stroma contained populations of AR susceptible and refractory to solubilization with KC1 and nuclease. Nuclease- and salt-sensitive populations of AR were similar numerically. The observed variability in epithelial cell nuclear AR was attributable to a wide range of solubilizable AR. Nuclease-digestion profiles and sedimentation analyses revealed that this wide range was not due to AR associated with soluble chromatin oligomers but to AR not detectably associated with other nuclear components. In contrast, AR in stromal cell nuclei was predominantly resistant to KC1 and nuclease, and variability in total nuclear AR concentration was due to variation in the nonextractable population.

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Section: Discussionmentioning

confidence: 99%

Association states of androgen receptors in nuclei of human benign hypertrophic prostate

Kyprianou

Davies

1986

The Prostate

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“…In mixtures the concen¬ tration of androgen-receptor complexes was 2 nmol/1, based on specifically bound radioactivity, and the concentration of DNA was 3-5 nmol/1, calculated on the basis that 1 mol plasmid DNA = 2-83 IO6 g. For the purposes of determining the sedimentation rate of DNA and its position in parallel gradients identical to those used to resolve mixtures, tracer amounts of DNA, nick-translated using [32P]dCTP, were included in some analyses, (a) Composite of three separate gradients in which were analysed [32P]DNA alone ( ) and [3H]DHT-receptor complexes, released from benign hypertrophic prostate (BPH) nuclei before digestion with micrococcal nuclease, alone (·) or after incubation with plasmid DNA (O), (b) Sedimentation analyses after incubation with DNA of trypsin-released nuclease-resistant [3H]DHT-receptor complexes from BPH (O) and prostate carcinoma (·) nuclei. receptors was dissimilar to both of these, reflecting neither the 1:1 distribution in rat prostate nuclei (see also Barrack & Coffey, 1980, 1982Rennie et al 1983) nor the excess of solubilized material from BPH nuclei (see also Grimaldo & Meikle, 1984). The predomi¬ nance of nuclease-resistant androgen receptors per¬ sisted over a wide range of total nuclear androgen receptor concentration (Table 1).…”

Section: Discussionmentioning

confidence: 88%

“…Both cancer and benign prostate hypertrophy (BPH) are conditions in which nuclear androgen receptors may differ quantitatively or in intranuclear deploy¬ ment from the normal condition Donnelly, Lakey & McBlain, 1984;Grimaldo & Meikle, 1984;Benson, Utz, Holicky & Veneziale, 1985). Such anomalies may be related to the aetiology of the diseases, and comparisons between the two may yield information on the disparate development of the two conditions.…”

Section: Introductionmentioning

confidence: 98%

Intranuclear distribution of androgen receptors in human prostate carcinoma

Kyprianou¹,

Gingell²,

Davies³

1987

Journal of Endocrinology

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Androgen receptors in nuclei from human prostate carcinomas were characterized on the basis of their solubilization by, or resistance to, micrococcal nuclease. By this means, androgen receptors were assigned to three nuclear categories: those associated with nuclease-resistant structures, those associated with chromatin and those apparently uncommitted by association with either of these. Prostate carcinoma nuclei contained high concentrations (57-82% of total nuclear content) of nuclease-resistant androgen receptors. This was a different pattern from that observed previously for benign hypertrophic prostate epithelial nuclei which contained a variable high proportion of uncommitted androgen receptors. The differences could not be attributed to differential losses to cytosol, or to loss of functionality, as determined in vitro. The differences in distribution could reflect different responses of diseased cells to androgens, or the intervention of other factors more relevant to the disease process.

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“…These problems are now rendered less significant by the availability of the synthetic androgen methyltrienolone (R1881), which does not bind to SHBG [ 171, and by the demonstration that sodium molybdate is a good stabilizing agent for androgen receptors [ 18, 191. Using these tools, androgen receptors have been adequately analyzed and quantitative differences have been reported between nuclei from normal and malignant prostatic specimens [20-231. Increased levels of nuclear androgen receptors were also demonstrated in the hyperplastic prostate [20,[22][23][24][25]. No significant difference was found in the receptor content in cytosolic fractions obtained from normal BPH and cancer tissues [25].…”

Section: Introductionmentioning

confidence: 99%

Characterization of androgen receptors in normal and malignant human prostatic tissues

et al. 1986

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The aim of this work was to study the physico-chemical characteristics of androgen receptors of normal and malignant human prostatic tissues. Association (k+1) and dissociation (k-1) rate constants and sedimentation profiles on sucrose density gradients were determined on [3H]androgen receptor complexes. In the presence of 20 mM sodium molybdate, no significant difference in k+1 and k-1 values could be found between cytosolic receptor preparations from normal and malignant specimens. The values obtained for k+1 (mean +/- SD) were 5 +/- 2 X 10(6)M-1 min-1 (N = 3) and 5 +/- 2 X 10(6)M-1 (N = 5); k-1 values of 23 +/- 4 X 10(-4) min-1 (N = 4) and 25 +/- 3 X 10(-4) min-1 (N = 5) were obtained for normal and malignant tissues respectively. Similar Nmax values were also obtained for normal [(mean +/- SD) 26 +/- 10 fmol/mg cytosolic protein (N = 5)] and malignant [20 +/- 9 fmol/mg protein (N = 7)] tissues. A statistically significant difference was found however, between k-1 values measured on [3H]androgen receptor complexes of nuclear extracts; values of 15 +/- 3 X 10(-4) min-1 (N = 4) and 9 +/- 1 X 10(-4) min-1 (N = 6) were found for normal and malignant tissue preparations respectively. This was also accompanied by a higher level of androgen receptors in nuclear extracts of malignant [Nmax, 308 +/- 171 fmol/g of tissue (N = 8)] compared to normal [Nmax, 68 +/- 11 fmol/g of tissue (N = 5)] tissues. The cytosolic [3H]androgen receptor complexes prepared from normal tissues sedimented mainly in the 8-9S area on sucrose density gradient whereas those from malignant tissues sedimented 50% in the 8-9S area and 50% in the 4S area. In conclusion, in this study, we found a different sedimentation profile of androgen-receptor complexes from the cytosol of prostatic cancers compared to normal as well as a diminution of their dissociation rate constant in nuclei.

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Increased levels of nuclear androgen receptors in hyperplastic prostate of aging men

Cited by 8 publications

References 13 publications

Association states of androgen receptors in nuclei of human benign hypertrophic prostate

Association states of androgen receptors in nuclei of human benign hypertrophic prostate

Intranuclear distribution of androgen receptors in human prostate carcinoma

Characterization of androgen receptors in normal and malignant human prostatic tissues

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