The Role of Receptors in the Anabolic Action of Androgens
19
Citation
73
Reference
10
Related Paper
The androgen receptor has been purified in the ‘70s and cloned in the ‘80s. It is a member of the steroid receptor superfamily and mediated the most important effects of androgen in androgen dependent or sensitive tissues. Several physiological function of the brain are differentially controlled in the two sexes and androgens play specific role in the processes of sexual differentiation and it is involved in the maintenance of male sex behaviour in adulthood. When mutated, the androgen receptor may impact on many of these androgen-regulated activities because of a loss of androgenic function in target cells. However, in the case of a peculiar type of mutation, the elongation of the polyglutamine tract normally present in its N-terminus, the androgen receptor becomes neurotoxic and induces cells death of a number of motoneurons in the spinal cord, which express very high level of this protein. Here, we will briefly discuss the most important actions of androgen receptor-mediated androgen activity in the brain and the mechanisms by which the mutant androgen receptor may lead to neurodegeneration in Spinal and Bulbar Muscular Atrophy (SBMA).
Cite
Citations (0)
Androgen receptors(AR) were found in many tissues. And androgen receptor exert its biological effect by binding with androgen. Androgen receptors were influenced by a lot of substance. Among them, androgen plays an important role in the field. For example, androgen can alter the amount, the metabolism and the structure of AR. The influence of androgen on the androgen receptors is reviewed.
Cite
Citations (0)
Flutamide
Dihydrotestosterone
Cite
Citations (12)
Journal Article Decreased Levels of the Androgen Receptor in the Mature Rat Phallus Are Associated with Decreased Levels of Androgen Receptor Messenger Ribonucleic Acid Get access KAREN K. TAKANE, KAREN K. TAKANE 1Department of Internal Medicine, University of Texas Southwestern Medical CenterDallas, Texas 75235-8857 Search for other works by this author on: Oxford Academic Google Scholar JEAN D. WILSON, JEAN D. WILSON 1Department of Internal Medicine, University of Texas Southwestern Medical CenterDallas, Texas 75235-8857 Search for other works by this author on: Oxford Academic Google Scholar MICHAEL J. McPHAUL MICHAEL J. McPHAUL 1Department of Internal Medicine, University of Texas Southwestern Medical CenterDallas, Texas 75235-8857 Search for other works by this author on: Oxford Academic Google Scholar Endocrinology, Volume 129, Issue 2, 1 August 1991, Pages 1093–1100, https://doi.org/10.1210/endo-129-2-1093 Published: 01 August 1991 Article history Received: 15 January 1991 Published: 01 August 1991
Glans
Cite
Citations (39)
The objective of this study was to determine whether androgen receptor levels in a transplantable animal model of prostatic adenocarcinoma correlated with androgen responsiveness of the tumor. This is the first comparative study of androgen receptor levels in 3 subcellular compartments (cytosol, nuclear salt-extractable and nuclear salt-resistant fractions) of 4 Dunning R3327 rat prostatic adenocarcinoma sublines that vary in their response to androgen ablation. Tumors were harvested from intact adult male rats in order to best approximate the human clinical setting in which receptor levels are quantitated prior to androgen ablative therapy. Only the nuclear salt-resistant (nuclear matrix) and total nuclear androgen receptor contents were significantly different among all tumor sublines. The properties of the tumors studied and their nuclear salt-resistant androgen receptor levels were as follows: H tumor--well-differentiated, slow growing, androgen-dependent, 63 +/- 11 fmol./mg. DNA; HI tumor--well-differentiated, slow growing, androgen-insensitive, 19 +/- 8 fmol./mg. DNA; G tumor--poorly-differentiated, fast growing, androgen-sensitive, 195 +/- 42 fmol./mg. DNA; and AT-2 tumor--anaplastic, fast growing, androgen-insensitive, no detectable receptors. There was no apparent quantitative relationship between androgen receptor content and tumor growth rates, which varied considerably irrespective of the androgen responsiveness of the tumor. However, there was a qualitative relationship between nuclear salt-resistant or total nuclear receptor content and androgen responsiveness. Higher levels of receptor (H and G tumor sublines) were associated with responsiveness to androgen ablation (cessation or slowing of growth, respectively), whereas lower levels of receptor (HI and AT-2 sublines) were associated with androgen insensitivity. These observations, based on relatively homogeneous tumors, may have important implications for human prostatic cancers which appear to be composed of heterogeneous cell populations.
Cite
Citations (48)
Recent research provides a more detailed understanding of the androgen and androgen receptor system role in mammalian female physiology indicating the essential value in reproduction. Here, we summarize androgen and androgen receptor biochemical and immunohistochemical brain studies of different vertebrate classes and, in detail, our investigations conducted on the female of the seasonal breeders, the amphibian anura Rana esculenta and the reptile, Podarcis sicula. The results have been achieved seasonally through plasma steroid radioimmunoassay and brain androgen binding activity by biochemical identification as well by androgen receptor immunolocalization and neuroanatomical distribution. Taken together, the seasonal fluctuations and the signal intensity in the different target cells of established encephalic district extend knowledge of the central action of the androgen in the lower vertebrate providing considerable understanding of the physiology role of the androgen/androgen receptor system in the female lower vertebrate reproduction.
Cite
Citations (0)
We investigated bcl-2 and androgen receptor (AR) expression in an androgen-independent subline derived from mouse androgen-dependent mammary carcinoma cells. The androgen-independent SCAI cells were subcloned by cultivating androgen-dependent SC2G cells in serum-free, androgen-free conditions. The growth of the SCAI cells was not affected by testosterone. Western blot analysis showed greater expression of Bcl-2 protein in SCAI cells than in SC2G cells. A four-day culture with 4 microM antisense oligonucleotide complementary to mouse bcl-2 significantly decreased the viability of SCAI cells, when compared with sense control. The amount of the AR-mRNA expression in SCAI cells was slightly weaker. Direct sequence analysis showed no mutations in the AR of either androgen-dependent or -independent cells. These data indicate that the increased expression of Bcl-2 protein plays an important role in acquiring tolerance for the testosterone ablation, although it is not related to AR gene alteration.
Cite
Citations (2)
Although androgens have myriad effects on the skeleton, the regulation of androgen action in bone is not well understood. Androgen receptors (ARs) are known to play an important role in mediating androgen action. We have examined the effects of androgens and other sex steroids on AR levels in osteoblastic cells in vitro using two clonal human cell lines, SaOS-2 and U-2 OS. AR protein levels were quantitated both by specific androgen binding studies and Western analyses, and AR messenger RNA was measured with RNase protection assays. Potential changes in AR functionality was assessed by reporter assays. Treatment of osteoblastic cells with the nonaromatizable androgen 5alpha-dihydrotestosterone (DHT) increased specific androgen binding 2-to 4-fold. Similar increases in AR protein levels were documented by Western analysis in both cell lines. The androgen-mediated increase in receptor levels was time and dose dependent as well as androgen specific. Steady-state AR messenger RNA levels were also increased by DHT. When AR concentrations in osteoblastic cells were elevated with exogenous receptor, there was an enhancement of DHT responsiveness, measured by increased trans-activation of an androgen-responsive promoter. Thus, androgen exposure increased androgen receptor protein levels and specific androgen binding in osteoblastic cells. Androgen action as measured by androgen-mediated transcriptional activation is enhanced in the presence of elevated AR levels. Consequently, these studies have revealed an additional means by which androgens may modulate skeletal metabolism.
Dihydrotestosterone
Cite
Citations (36)
Thermolabile
Androgen insensitivity syndrome
RNF4
Cite
Citations (0)