Autoregulation of androgen receptor in rat ventral prostate: involvement of c-fos as a negative regulator.
Recent work from our laboratory has focused on elucidating the mechanism of androgen regulation of the androgen receptor (AR). We have demonstrated that testosterone increases AR protein and binding within 1 h in the ventral prostate of adult rats castrated for 24 h. Cycloheximide administered with testosterone reduces AR and AR mRNA levels. AP-1/c-fos transcription factor has been shown to function as a negative in many systems. c-fos mRNA levels were decreased 1 h after testosterone treatment in the ventral prostate, whereas they were increased in cycloheximide alone or cycloheximide-testosterone treated groups as compared to vehicle control. c-fos protein was also increased in the testosterone-cycloheximide treated group as compared to testosterone alone or cycloheximide alone groups at 1 h. By 3 h, the tissue recovers from the inhibitory effect of cycloheximide as evidenced by restoration of AR and an increase in AR mRNA levels. At this time c-fos protein levels were reduced after treatment with cycloheximide and testosterone and c-fos mRNA levels were comparable to the controls. These results suggest that elevation of c-fos expression is associated with a decrease in AR and mRNA and provide correlative data supporting negative repression by c-fos on androgen receptors levels. Between the age of 25-85 days, serum testosterone levels reached adult levels by the age of 55 days. Steady-state AR mRNA levels increased significantly by the age of 85 days while c-fos mRNA levels remained at low baseline levels at all ages. Thus, in addition to the circulating levels of serum testosterone, other age related factors are also involved in the regulation of AR mRNA levels. Furthermore, androgens appear to maintain androgen receptor levels and androgen sensitivity by continuous suppression of the repressor, c-fos.
Mora
G R
GR
Department of Physiology and Endocrinology, Medical college of Georgia, Augusta 30901-3000, USA.
Mahesh
V B
VB
D000367:Age Factors; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D003513:Cycloheximide