Effects of 17 alpha-methyltestosterone on uterine morphology and heat shock protein expression are mediated through estrogen and androgen receptors.
Testosterone and the synthetic androgen, 17 alpha-methyltestosterone (MT), have been shown to increase uterine weights and alter uterine morphology. However, whereas the mechanism of action of testosterone in the uterus has been studied, it is not known if the actions of MT are mediated through androgen (AR) or estrogen (ER) receptors. In the present study, we have shown that MT, at 0.5 or 10 mg/kg per day, increases uterine weight and alters uterine morphology in a dose-dependent manner. Co-administration of the anti-androgen, flutamide, or the anti-estrogen, ICI 182,780, with MT revealed that the effects of the low dose of MT are mediated through the ER, whereas those of the high dose are mediated through both the ER and AR. In addition, we have studied the effects of MT on uterine heat shock proteins (hsps), a group of estrogen-regulated proteins whose levels increase in response to growth signals and protein damage. MT increased levels of hsp90 alpha, hsp72, and grp94. All effects on uterine hsp levels were antagonized by the anti-estrogen and not the anti-androgen. Collectively, the results of the present study indicate that the effects of MT in the uterus are mediated through the AR and ER.
Papaconstantinou
Andriana D
AD
Department of Biological Sciences, George Washington University, 332 Lisner Hall, 2023 G. St. N.W., DC 20052, USA.
Umbreit
Thomas H
TH
Goering
Peter L
PL
Brown
Ken M
KM
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D000077267:Fulvestrant; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism; D008777:Methyltestosterone / Q000494:pharmacology*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D045165:Testosterone Congeners / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D045165:Testosterone Congeners; C018551:glucose-regulated proteins; D000077267:Fulvestrant; D004958:Estradiol; D005485:Flutamide; D008777:Methyltestosterone