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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

If the above two hypotheses are correct, they would require at least one more specific nuclear receptor for T, and at least one membrane receptor to account for the very rapid effects induced by androgens on certain target tissues. If this is the case, clearly a single androgen receptor will not fill the bill.
Mol Cell Endocrinol 1991 Apr
PMID:Can a single androgen receptor fill the bill? 182 Sep 65

We have examined the effect of androgen treatment on androgen receptor mRNA and protein expression in the LNCaP human prostate carcinoma cell line. Incubation with androgen caused a decrease in cellular androgen receptor mRNA content that was concentration and time dependent. Maximal suppression to approximately 35% of control level was observed after 49 h of exposure to androgen. By contrast, incubation of LNCaP cells with androgen resulted in a 2-fold increase in the cellular content of androgen receptor protein at 24 h. At 49 h androgen receptor protein increased 30% as assayed by immunoblots and 79% as assayed by ligand binding. These results suggest that ligand-induced changes in androgen receptor stability and/or the translational efficiency of androgen receptor mRNA account for the phenomenon of androgen receptor upregulation observed in cultured LNCaP cells. Furthermore, the suppression of androgen mRNA and protein that is caused by prolonged incubation with androgen is incomplete and is reversible upon removal of ligand.
Mol Cell Endocrinol 1991 Apr
PMID:Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells. 182 Sep 79

Diabetes was induced in male Sprague-Dawley (S-D) rats by streptozotocin (STZ) administration. Following STZ injection, plasma glucose levels in the treated rats were significantly elevated from values of untreated controls. Over the experimental period (140 days) plasma testosterone (T) levels, prostatic nuclear androgen receptor (AR) contents and prostatic weights declined with increasing age in the rats. The declines in both STZ-treated and untreated rats were similar in manner and no notable differences were discerned in the data obtained from the two groups. On the contrary, prostatic cytosolic AR contents in untreated rats remained unchanged with advancing age, but was reduced to 50% of normal control values in diabetic rats following STZ treatment. Correlation analyses revealed that prostatic nuclear AR contents correlated positively with plasma T levels while prostatic cytosolic AR contents correlated negatively with plasma glucose levels. These data support former claims that prostatic nuclear AR content is dependent on circulating T level and suggest a possible link between prostatic cytosolic AR content and plasma glucose concentrations.
J Steroid Biochem Mol Biol 1991 Jan
PMID:Prostatic androgen receptor and plasma testosterone levels in streptozotocin-induced diabetic rats. 182 71

Antiglucocorticoid and antiprogestin RU38486 (RU486) stimulated the growth of highly androgen- and moderately glucocorticoid-sensitive SC-3 cells (a cloned cell line from Shionogi mouse mammary carcinoma 115) in a dose-dependent manner. A maximal 8-fold stimulation of growth by RU486 has been observed at 10(-7) M in a serum-free medium and its potency has been found to be almost the same as that of dexamethasone (Dex). The growth rate of SC-3 cells treated by triamcinolone acetonide (TA) or Dex combined with RU486 at 10(-9)-10(-7) M was enhanced compared to cells treated by TA or Dex alone, indicating that RU486 had additive rather than antagonistic effects. Our previous study revealed that RU486 could compete with the specific uptake of [3H]testosterone in intact SC-3 cells at relatively low affinity and the present study showed that the stimulatory effect of RU486 on the growth of SC-3 cells was significantly inhibited by pure antiandrogen flutamine and that half-maximal inhibition by flutamine was achieved at 10(-6) M. Moreover, we demonstrated that the conditioned medium from RU486-stimulated SC-3 cells contained growth-promoting activity which caused a 3.5-fold increase in DNA synthesis by SC-3 cells in the absence of RU486 and which was abolished by treatment with heparin-Sepharose. These results indicate that RU486-induced growth of SC-3 cells may be expressed as an androgenic activity through androgen receptor and mediated by a heparin-binding growth factor.
J Steroid Biochem Mol Biol 1991 Sep
PMID:Non-classical androgenic actions of RU38486 in androgen-responsive Shionogi carcinoma 115 cells in serum-free culture. 191 22

Androgen receptor synthesis and modification were studied in the human LNCaP cell line. Immunoblotting with a specific polyclonal antibody showed that the androgen receptor migrated as a closely spaced 110-112 kDa doublet on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. Most of the receptor protein is present in the higher molecular mass form. Pulse labelling experiments with [35S]methionine showed that the androgen receptor is synthesized as a single 110 kDa protein which is rapidly converted to a 112 kDa protein. Alkaline phosphatase treatment of cytosols from [35S]methionine pulse labelled cells caused a gradual elimination of the 112 kDa isoform with a concomitant increase of the 110 kDa isoform. This indicates that the observed 110 to 112 kDa upshift of the newly synthesized androgen receptor reflects receptor phosphorylation. Both isoforms can bind hormone and can undergo a hormone dependent transformation to a tight nuclear binding form, indicating that the 110 to 112 kDa conversion is not an obligatory step for hormone binding or receptor transformation.
Mol Cell Endocrinol 1991 Sep
PMID:Synthesis and post-translational modification of the androgen receptor in LNCaP cells. 195 82

It has been previously shown that estrogens may exert their action on human breast cancer cells through coordinated control of secreted growth factors which act in an autocrine and paracrine fashion. Growth stimulation of the androgen receptor negative prostate carcinoma cell line DU-145 by dihydrotestosterone in the presence of the androgen-responsive human prostate carcinoma cell line LNCaP now indicates that androgens may regulate growth of prostate carcinoma cells through related mechanisms. A variety of androgen-regulated growth modulatory activities with autocrine and paracrine potential can be detected in conditioned media from LNCaP cells partially purified by ion exchange chromatography. Androgen-induced growth of LNCaP cells is partially inhibited by the polyanions suramin and dextran sulfates which antagonize growth factor action. These data suggest the existence of at least two different mechanisms of growth regulation by androgen which can be distinguished by their different sensitivity to growth factor inhibitory agents. We conclude that the combination of antipeptidergic substances and androgen withdrawal would represent a new and promising strategy for treatment of human prostate cancer.
J Steroid Biochem Mol Biol 1991
PMID:Growth factors in human prostate cancer cells: implications for an improved treatment of prostate cancer. 195 19

The mitogenic activity of several growth factors on androgen responsive LNCaP human prostate tumor cells was studied. A two-fold stimulation of cell proliferation was observed after a culture period of 6 days in 1 ng EGF/ml, 10 ng TGF-alpha/ml or 20 ng basic FGF/ml. TGF-beta (0.02 ng/ml), which did not affect cell proliferation when added alone to the culture medium, inhibited the EGF- and TGF-alpha-induced growth. The synthetic androgen R1881 (0.1 nM) stimulated cell proliferation three-fold and increased the number of EGF receptors from 11500 to 28500 sites/cell. One of the mechanisms involved in androgen action on these cells is therefore an increased EGF receptor expression and increased sensitivity to EGF. TGF-beta did not directly affect androgen-responsive growth but inhibited the synergistic effect of EGF. A considerable expression of TGF alpha (precursors) could be demonstrated on the cells by immunohistochemical staining. However the staining intensity was not affected by androgens. These results make it less likely that androgen-responsive growth is mediated by regulation of secretion of an EGF- or TGF alpha-like activity, which in turn acts in an autocrine manner to stimulate growth. Estrogens, progestagens and antiandrogens do not inhibit androgen responsive growth of LNCaP cells but have striking growth stimulatory effects, increase EGF receptor level and increase acid phosphatase secretion. LNCaP cells contain a modified androgen receptor system with respect to both steroid specificity and antiandrogen sensitivity. It has recently been shown that the stimulatory effects are due to a mutated amino acid in the steroid binding domain of the androgen receptor.
J Steroid Biochem Mol Biol 1991
PMID:Regulation of growth of LNCaP human prostate tumor cells by growth factors and steroid hormones. 195 20

The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of the genomic organization of the corresponding gene has enabled us to study androgen receptors in subjects with the clinical manifestation of androgen insensitivity and in a human prostate carcinoma cell line (LNCaP). Using PCR amplification, subcloning and sequencing of exons 2-8, we identified a G----T mutation in the androgen receptor gene of a subject with the complete form of androgen insensitivity, which inactivates the splice donor site at the exon 4/intron 4 boundary. This mutation causes the activation of a cryptic splice donor site in exon 4, which results in the deletion of 41 amino acids from the steroid binding domain. In two other independently arising cases we identified two different nucleotide alterations in codon 686 (GAC; aspartic acid) located in exon 4. One mutation (G----C) results in an aspartic acid----histidine substitution (with negligible androgen binding), whereas the other mutation (G----A) leads to an aspartic acid----asparagine substitution (normal androgen binding, but a rapidly dissociating androgen receptor complex). Sequence analysis of the androgen receptor in human LNCaP-cells (lymph node carcinoma of the prostate) revealed a point mutation (A----G) in codon 868 in exon 8 resulting in the substitution of threonine by alanine. This mutation is the cause of the altered steroid binding specificity of the LNCaP-cell androgen receptor. The functional consequences of the observed mutations with respect to protein expression, specific ligand binding and transcriptional activation, were established after transient expression of the mutant receptors in COS and HeLa cells. These findings illustrate that functional errors in the human androgen receptor have an enormous impact on phenotype and fertility.
J Steroid Biochem Mol Biol 1991
PMID:Androgen receptor abnormalities. 195 38

Extracellular androgen-binding proteins (ABPs) are thought to modulate the regulatory functions of androgens and the trans-acting nuclear androgen receptor. Testicular ABP and plasma sex hormone-binding globulin (SHBG), which is produced in the liver, are encoded by the same gene. We report here that the ABP/SHBG gene is also expressed in fetal rat liver and adult brain. Immunoreactive ABP was localized in the brain and fetal liver and mRNAs were identified in both tissues by northern blot hybridization. Analysis of brain and fetal liver cDNA clones revealed alternatively processed RNAs with sequence characteristics suggesting the encoded proteins could act as competitors of ABP/SHBG binding to cell surface receptors. One cDNA represented a fused transcript of the ABP/SHBG gene and the histidine decarboxylase gene that was apparently formed by a trans-splicing process. Gene sequencing experiments indicate that tissue-specific ABP/SHBG gene promoter-enhancer elements are utilized in testis, brain and fetal liver. These data demonstrate that the structure, RNA transcript processing and likely regulation of the ABP/SHBG gene are very complex.
J Steroid Biochem Mol Biol 1991
PMID:Complex structure and regulation of the ABP/SHBG gene. 195 75

Human genital skin fibroblasts (GSF) make a relatively abundant 56/58 kDa protein that binds androgens. The protein shares many properties with the approximately 100 kDa androgen receptor that is encoded by a locus in the q12 region of the X chromosome. It does not appear to be androgen-induced, yet is absent in GSF of most patients with complete androgen insensitivity (CAI). A precursor-product relation with the androgen receptor (AR) protein has been largely excluded; that it may be an unorthodox product of the AR gene has not. The 56/58 kDa protein is made by the GSF of a mentally retarded subject who has CAI because of a complete deletion of the coding portion of the AR gene. Hence, the strong constitutional and statistical correlations that have been demonstrated between the two proteins cannot arise because they share the same gene. The subject's genomic DNA hybridizes normally with 11 single-copy probes from Xq11-Xq13. Therefore, we cannot attribute her mental retardation to a contiguous gene syndrome.
Mol Cell Endocrinol 1991 Jan
PMID:The 56/58 kDa androgen-binding protein in male genital skin fibroblasts with a deleted androgen receptor gene. 205 Feb 65


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