Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the androgen receptor (AR) gene is regulated by androgens. Although androgens down-regulate AR mRNA in most cell lines and tissues, including the prostate, up-regulation occurs in some tissues. Androgen-mediated reduction in AR mRNA is reproduced in COS1 cells and in the androgen-sensitive human prostate cancer cell line LNCaP when each expresses the AR cDNA. We have previously established that the AR cDNA contains the requisite sequences for this down-regulation. Here we shown that androgen promoted up-regulation of AR mRNA in two androgen-independent human prostate cancer cell lines, PC3 and DU145, when each was transfected with a human AR cDNA. This effect was due to the AR cDNA and not to the heterologous promoter driving AR expression. In addition to up-regulation of AR mRNA, androgen induced comparable increases in AR protein levels in PC3 cells stably expressing an AR cDNA (PC3/AR). Up-regulation of AR in PC3/AR cells was accompanied by failure of these cells to undergo desensitization or inactivation of AR following prolonged (96 h) androgen administration, whereas the same conditions resulted in desensitization of AR transactivation in LNCaP cells and in CVl cells that stably express the AR cDNA. Androgen treatment of PC3/AR cells resulted in induction of an androgen-regulated reporter gene (MMTV-CAT) as well as the native prostate-specific antigen gene, which is silent in untransfected PC3 but is androgen up-regulated in LNCaP and in the prostate. These results suggest that ectopic expression of AR in androgen-independent prostate cancer cell lines establishes both typical and atypical androgenic responses in a target gene-specific manner. Androgenic up-regulation of AR cDNA expression may be due to distinct signaling mechanisms that influence androgen action in androgen-independent prostate cancer cells.
Steroids 1996 Sep
PMID:Androgenic up-regulation of androgen receptor cDNA expression in androgen-independent prostate cancer cells. 888 19

The syntheses of three 11 beta-aryl-19-norpregna-4,9-dien-3-one derivatives with 17-spirolactone and 17 beta-hydroxy-17 alpha-cyanoethyl substitutions are described. The progesterone agonist/antagonist activities of the new compounds are investigated using a recently developed tissue culture system that relies on the progesterone agonist up-regulation of the prostate-specific antigen (PSA) gene in female breast tumor cell lines. Two of the newly synthesized compounds exhibit mixed agonistic/antagonistic progestational activity.
Steroids 1998 Oct
PMID:New 11 beta-aryl-substituted steroids exhibit both progestational and antiprogestational activity. 980 Feb 83

We describe a 72-year-old man with prostate enlargement, prostate-specific antigen level of 35 ng/dl, mild polyarthritis, and constitutional symptoms. Prostatic ultrasonography suggested neoplasm; however, transrectal biopsy revealed findings consistent with polyarteritis nodosa (PAN). The patient went on to develop leg paresthesia and dysesthesia, increased serum creatinine, and systemic hypertension. Steroids and intravenous cyclophosphamide were administered, followed by improvement. Our case emphasizes the protean onset of PAN, and provides a new differential diagnosis of prostatic diseases related to elevated prostate-specific antigen.
 ...
PMID:Polyarteritis nodosa mimicking prostatic cancer. 1103 51

Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3beta,17beta-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3beta-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3beta-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer.
 ...
PMID:C19-steroids as androgen receptor modulators: design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists. 1675 73

The factual impact of endogenously activated AHR by 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand of AHR on androgen receptor (AR) was aim of this study. In this study, LNCaP cells were exposed to FICZ, CH223191 and flutamide (Flu) alone or in combination in the presence and absence of testosterone. CYP1A1 enzyme activity, cell viability, cellular prostate-specific antigen (PSA) and dihydrotestosterone (DHT) production, mRNA levels of PSA, KLK2, TMPRSS2, and AR genes were measured as endpoints. A declining in the expression of androgen- responsive target genes was seen by either Flu or FICZ in the presence of testosterone. Furthermore, the forced decrease in the expression of AR target genes resulted in 41% and 31% decline in the DHT and PSA concentrations respectively. Taken together, endogenously activated AHR plays a regulatory role on AR. Therefore, FICZ might be an effective chemical in treating prostate cancer.
Steroids 2020 01
PMID:Anti-androgenic effect of 6-formylindolo[3,2-b]carbazole (FICZ) in LNCaP cells is mediated by the aryl hydrocarbon-androgen receptors cross-talk. 3158 5