PUBLICATION

Molecular cloning and characterization of a nuclear androgen receptor activated by 11-ketotestosterone

Authors
Olsson, P.E., Berg, H., von Hofsten, J., Grahn, B., Hellqvist, A., Larsson, A., Karlsson, J., Modig, C,, Borg, B., and Thomas. P.
ID
ZDB-PUB-050823-1
Date
2005
Source
Reproductive Biology and Endocrinolgy   3: 37 (Journal)
Registered Authors
von Hofsten, Jonas
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Cell Line
  • Cloning, Molecular
  • Dihydrotestosterone/metabolism
  • Female
  • Fish Proteins/biosynthesis
  • Gene Expression Regulation
  • Humans
  • Kidney/metabolism
  • Male
  • Molecular Sequence Data
  • Receptors, Androgen/drug effects
  • Receptors, Androgen/genetics*
  • Receptors, Androgen/metabolism
  • Sequence Alignment
  • Signal Transduction
  • Smegmamorpha
  • Testosterone/analogs & derivatives*
  • Testosterone/pharmacology
  • Transcriptional Activation
PubMed
16107211 Full text @ Reprod. Biol. Endocrinol.
Abstract
Although 11-ketotestosterone is a potent androgen and induces male secondary sex characteristics in many teleosts, androgen receptors with high binding affinity for 11-ketotestosterone or preferential activation by 11-ketotestosterone have not been identified. So, the mechanism by which 11-ketotestosterone exhibits such high potency remains unclear. Recently we cloned the cDNA of an 11-ketotestosterone regulated protein, spiggin, from three-spined stickleback renal tissue. As spiggin is the only identified gene product regulated by 11-ketotestosterone, the stickleback kidney is ideal for determination of the mechanism of 11-ketotestosterone gene regulation. A single androgen receptor gene with two splicing variants, belonging to the androgen receptor-beta subfamily was cloned from stickleback kidney. A high affinity, saturable, single class of androgen specific binding sites, with the characteristics of an androgen receptor, was identified in renal cytosolic and nuclear fractions. Measurement of ligand binding moieties in the cytosolic and nuclear fractions as well as to the recombinant receptor revealed lower affinity for 11-ketotestosterone than for dihydrotestosterone. Treatment with different androgens did not up-regulate androgen receptor mRNA level or increase receptor abundance, suggesting that auto-regulation is not involved in differential ligand activation. However, comparison of the trans-activation potential of the stickleback androgen receptor with the human androgen receptor, in both human HepG2 cells and zebrafish ZFL cells, revealed preferential activation by 11-ketotestosterone of the stickleback receptor, but not of the human receptor. These findings demonstrate the presence of a receptor preferentially activated by 11-ketotestosterone in the three-spined stickleback, so far the only one known in any animal.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping