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

Castration-induced androgen deprivation leads to the activation of the programmed death of the androgen-dependent prostatic epithelial cells in the rat ventral prostate. In order to identify potential mediators of this programmed cell death, the expression of transforming growth factor-beta (TGF beta) in the rat ventral prostate was studied, after castration induced-androgen withdrawal. Steady state levels of TGF beta mRNA were determined by Northern blot analysis and compared with mRNA levels for prostatein C3, the major androgen-dependent secretory protein of ventral prostate and also with mRNA levels for TRPM-2, a gene that is specifically expressed during castration induced prostatic cell death. Within the first day after castration there was a dramatic increase in the levels of TGF beta mRNA in the ventral prostate (approximately 10-fold) and by 4 days after castration TGF beta mRNA was maximally expressed (approximately 40-fold increase), by which time the androgen-dependent C3 secretory protein mRNA transcripts have diminished to undetectable levels. Androgen administration to 4-day castrated rats led to a marked decrease in TGF beta mRNA to a level comparable to its constitutive expression obtained in the intact control animals, indicating that expression of TGF beta in the rat ventral prostate is under negative androgenic regulation. The transcript levels encoding TRPM-2 initially increased 10-fold within the first day after castration and by day 4 post castration there was a dramatic increase (approximately 50-fold) which correlated well with the maximal rate of cell death of the androgen-dependent prostatic epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Oct
PMID:Expression of transforming growth factor-beta in the rat ventral prostate during castration-induced programmed cell death. 260 47

Androgen control of the RP2 gene in the mouse kidney has been modified during evolution. In inbred mice (Mus domesticus), the concentrations of mRNAs encoded by RP2 undergo a 10- to 12-fold induction in response to testosterone; in other Mus species (e.g., Mus hortulanus and Mus caroli), induction ranges from none to about two- to fourfold. In this communication, we show that androgens induced RP2 transcription in M. domesticus, although this induction may not have fully accounted for the increase in mRNA levels. Reduced mRNA inducibility in M. hortulanus and in several other species was associated with an absence of transcriptional induction. Analysis of an interspecies backcross population indicated that the difference in RP2 inducibility between M. domesticus and M. hortulanus was due to a single Mendelian locus tightly linked (0 of 47 recombinants) to RP2. The RP2 gene was found to contain at least two promoters, only one of which was highly sensitive to testosterone. These results indicate that induction of the RP2 mRNAs, as well as interspecies variations in RP2 inducibility, are primarily a consequence of effects on this promoter.
Mol Cell Biol 1989 Feb
PMID:Molecular genetics of androgen-inducible RP2 gene transcription in the mouse kidney. 271 Jan 12

Androgen-binding protein (ABP) is a testicular Sertoli cell secretory protein that acts as a carrier of androgen in the male reproductive tract. ABP has been characterized from a wide range of animal species, including man, rabbit and rat. However, it has been widely accepted that mice do not produce testicular ABP. We have used immunological and molecular biological techniques to demonstrate that the ABP gene is expressed in the CD1 mouse. Steroid-binding, radioimmunoassay and immunocytochemical studies demonstrated that ABP is present in mouse testis and epididymis, but at 1/50 to 1/25 the level of rat epididymis. A 1.7 kilobase mRNA, homologous with rat ABP cDNA, was identified in mouse testis and Sertoli cells by Northern blot hybridization, but at a much lower level than in the rat. An ABP cDNA was isolated from a mouse testis cDNA library and encoded a protein (403 residues) with 89% of the amino acid residues identical to rat ABP, including a signal peptide. Our results indicate that ABP is expressed in the mouse and past failures to detect androgen-binding activity were due to the low level of ABP protein.
Mol Cell Endocrinol 1989 May
PMID:The androgen-binding protein gene is expressed in CD1 mouse testis. 275 30

Androgen dependent skin disorders are important in clinical practice. Effective topical antiandrogens would lead to a breakthrough in their treatment. Although many attempts have been performed to develop such compounds, major successes have not been forthcoming. In the present study three existing antiandrogenic molecules have been compared with regard to their effect on androgen metabolism, receptor competition and on histological parameters in the hamster flank organ test. It appears that the effect on the hamster pigmented spot can be predicted on the basis of molecular mechanism. However, the effects on histological parameters are apparently dependent on additional factors such as metabolism of the active substance before reaching the sebaceous structure or limited penetration through the skin surface. The results indicate that in the development of new antiandrogens pre-screening can be performed with the aid of metabolic and receptor studies, while the histological parameters in the hamster flank organ test provide an animal model with a good predictive value.
Mol Biol Rep 1986
PMID:Studies on the local activity of antiandrogens at the molecular and histological level. 294 58

The regulatory mechanism of hepatic sulfation of N-hydroxyarylamine and N-hydroxyarylamide by endocrine factors has been studied in rats. The cytosolic sulfations of N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) and 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), which were determined by the reductive formations of 2-acetylaminofluorene and Glu-P-1, were seven to nine times and three times higher, respectively, in male than female rats. Hypophysectomy of male rats decreased their activities to 23% and 41% of the levels of the untreated animals, respectively. Intermittent treatment of hypophysectomized male and female rats with human growth hormone (hGH) significantly increased their sulfating activities of both compounds. Infusion of hGH also enhanced the sulfating activity of N-hydroxy-AAF but not of N-hydroxy-Glu-P-1. The sulfating activity of N-hydroxy-AAF was also decreased by castration at neonate and was increased by the administration of testosterone propionate to gonadectomized male and female rats. Testosterone propionate and estradiol benzoate had no effect on hypophysectomized rats, but estradiol benzoate repressed the sulfating activities of N-hydroxy-AAF and N-hydroxy-Glu-P-1 in hGH-treated hypophysectomized male rats. These results indicate that sex steroids elicit their effects on the sulfations of N-hydroxyl-aryl compounds through modulating the action of growth hormone at hypothalamus-pituitary and hepatic levels in rat livers.
Mol Pharmacol 1987 Oct
PMID:Regulation of hepatic sulfotransferase catalyzing the activation of N-hydroxyarylamide and N-hydroxyarylamine by growth hormone. 347 84

The androgen dependence of a highly abundant mRNA found in the rat dorsolateral prostate and seminal vesicles has been investigated using a complementary DNA clone from a rat dorsal prostate library. The 1.5 kilobase (kb) mRNA codes for a 52 000 Da translation product which is processed to 49 000 Da in the presence of microsomal membranes. This product appears to correspond to the previously described SVS II protein secreted by rat seminal vesicles and can be immunoprecipitated with anti-SVS II antiserum. Dot hybridization assays indicated that the mRNA is abundant in the dorsal and lateral prostate glands and in seminal vesicles but not in the ventral prostate, coagulating gland or other non-accessory sex tissues. Castration of mature male rats reduces the 1.5 kb mRNA 10-fold in the seminal vesicles and 7-fold in the dorsolateral prostate in 9 days. Androgen administration to one-week castrates returned the mRNA level to normal in both tissues within 48 h. The levels of the 1.5 kb mRNA are very similar in the dorsolateral prostate and seminal vesicles at maturity but distinct patterns of developmental regulation of this gene exist in the two tissues. Between 3 and 6 weeks of age, the level of the 1.5 kb mRNA increases approximately 3-fold in the dorsolateral prostate while the increase in the seminal vesicles is more than 600-fold.
Mol Cell Endocrinol 1986 Oct
PMID:Effect of androgens on mRNA for a secretory protein of rat dorsolateral prostate and seminal vesicles. 375 73

Androgen-binding protein (ABP) is present in the guinea-pig testis, epididymis and epididymal fluid. Guinea-pig ABP sediments as an approx. 4.6S species on sucrose gradients containing 0.01 M KCl. Electrophoresis on non-denaturing polyacrylamide gels indicated that specific androgen binding was present in epididymal cytosol, but not in plasma. Time-course studies indicated that binding equilibrium is approached in about 2.5 h; the dissociation half-time of [3H]5 alpha-DHT from guinea-pig ABP is 5.64 +/- 0.62 h (n = 6) at 4 degrees C. The relative affinities of some steroids for guinea-pig ABP in relation to 5 alpha-DHT = 1 are: testosterone = 0.55 +/- 0.13 (n = 4), estradiol = 0.14 +/- 0.03 (n = 4), the anti-androgen cyproterone acetate = 0.0025 +/- 0.0002 (n = 3). Guinea-pig ABP exhibited an equilibrium dissociation constant of 6.34 +/- 0.52 nM (n = 3) at 4 degrees C and there were 3.43 +/- 0.78 (n = 3) pmoles of binding sites per mg of protein when homogenates of the whole epididymis were assayed. The concentration of ABP was lowest in the caput-corpus region of the epididymis, highest in the proximal cauda, and intermediate in the distal cauda. Essentially all of the ABP present in the distal cauda was intraluminal, as evidenced by the fact that flushing of the duct eliminated most of the [3H]5 alpha-DHT binding activity.
Mol Cell Endocrinol
PMID:The presence of androgen-binding protein in the guinea-pig testis, epididymis and epididymal fluid. 689 45

To study the mechanisms by which androgens intervene in the regulation of growth and differentiation of human prostatic epithelial cells, cDNA clones encoding putative prostate-secreted proteins were characterized and tested as potential markers for androgen action. One of the isolated cDNAs expressed diazepam-binding inhibitor/acyl-CoA-binding protein (DBI/ACBP), suggesting that this polypeptide, that has been implicated in a large number of biochemical processes, is expressed and secreted by prostate cells. As demonstrated by Northern blot analysis, the mRNA encoding DBI/ACBP was expressed in prostate tissue and in the three human prostatic adenocarcinoma cell lines tested: LNCaP, PC-3 and DU-145. In androgen-sensitive LNCaP cells, the synthetic androgen R1881 stimulated the DBI/ACBP steady state mRNA levels with half maximal effects at a concentration of 0.2 nM. Increases were a maximal 12 h after addition of the synthetic hormone. DBI/ACBP mRNA levels could also be stimulated by the synthetic androgen mibolerone and by the natural androgens testosterone and dihydrotestosterone. In agreement with the altered steroid specificity of the androgen receptor in LNCaP cells, estradiol and progesterone also exerted a stimulatory effect. Cortisol and the synthetic glucocorticoid dexamethasone were without effect. Androgen stimulation of DBI/ACBP mRNA levels was abolished in the presence of the protein synthesis inhibitor cycloheximide, implying a role for labile or androgen-induced proteins in this androgen stimulation. This is in contrast to the androgen stimulation of the mRNA encoding prostate-specific antigen (PSA), suggesting that different mechanisms are involved in the androgen regulation of these two genes. Although further experiments are required to confirm that DBI/ACBP is secreted by prostatic epithelial cells, these data demonstrate that the mRNA encoding DBI/ACBP is expressed in prostate cells and is affected by androgens in androgen-responsive LNCaP cells.
Mol Cell Endocrinol 1994 Sep
PMID:Androgen regulation of the messenger RNA encoding diazepam-binding inhibitor/acyl-CoA-binding protein in the human prostatic adenocarcinoma cell line LNCaP. 752 52

There is increasing evidence that the course of prostatic carcinoma is determined by a complex interplay between genetic events, paracrine interactions, and hormonal and dietary factors. These latter factors include several ligands of the nuclear receptor family such as androgens, vitamin D3 and retinoids. To test whether thyroid hormones also influence the growth and differentiated function of prostatic carcinoma cells, LNCaP cells were treated with or without triiodothyronine (T3) in the absence or in the presence of other regulatory factors. Exposure of LNCaP cells to T3 for 6 days in the absence of androgens caused a dose-dependent increase in [3H]-thymidine incorporation with a maximal stimulation of 2.5-fold at 10(-9) M T3. Secretion of prostate-specific antigen (PSA) was also stimulated 2-3-fold. The observed effects may well be mediated by a nuclear T3 receptor as evidenced by displaceable T3 binding studies. Combined treatment of LNCaP cells with androgens and T3 revealed intriguing interactions between these two pathways. Below and up to 10(-10) M of the synthetic androgen R1881, the concentration that evokes optimal proliferative responses, T3 stimulated [3H] thymidine incorporation. At higher concentrations of androgens, T3 displayed antiproliferative effects. No androgen-dependent effects on T3 receptor levels were observed. Conversely, T3 increased androgen receptor levels up to twofold. Androgen as well as T3 stimulation of proliferation was abolished by high concentrations of the retinoid 9-cis-retinoic acid. These data add T3 to the list of factors that influence growth and differentiation of prostatic tumor cells and contribute to our understanding of the intricate pathways that ultimately determine the course of prostatic carcinoma.
Mol Cell Endocrinol 1995 Mar
PMID:Triiodothyronine modulates growth, secretory function and androgen receptor concentration in the prostatic carcinoma cell line LNCaP. 754 May 69

A large family with androgen insensitivity syndrome (AIS) has been investigated, in order to detect carrier individuals and to investigate their AR binding. We have previously reported that different affected members of this family have different AR gene deletions, and, testing normal female relatives of the affected individuals, we have identified three heterozygote females all of whom carry a deletion of exon E of the AR gene. Androgen binding capacity was measured in cultured genital skin fibroblasts from normal male and female controls, the affected, and the heterozygote individuals in this family. A significant difference was found between the binding ranges for normal male foreskin and suprapubic skin fibroblasts (P < 0.005), and the three individuals with AIS had very low androgen binding capacity in their genital skin fibroblasts (2.6, 5.0, and 3.4 fmol 3HR1881/mg protein) compared to the normal range. The heterozygote females all had binding within the normal female suprapubic skin fibroblast range (12.5, 6.1, and 6.4 fmol 3HR1881/mg protein, respectively, for the three heterozygotes). Thus, we conclude that the absence of one functional AR gene in heterozygote females has not effect on AR binding capacity in cultured genital skin fibroblasts. In addition, bone mineral density was measured in the affected aunt and found to be significantly lowered at the lumbar spine (Z = -2.81) and hip (Z = -1.54); however, the role of the AR in determination of bone mineral density remains to be elucidated.
Biochem Mol Med 1995 Jun
PMID:Androgen receptor binding studies on heterozygotes in a family with androgen insensitivity syndrome. 755 23


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