Progesterone receptor regulation by 17 beta-estradiol in human endometrial carcinoma grown in nude mice.
Regulation of progesterone receptor (PR) in human endometrial carcinoma was investigated in vivo in a multisite nude mouse tumor experimental system by estrogen administration and withdrawal. The cytosolic PR concentration was low in tumors grown in the absence of 17 beta-estradiol, but increased rapidly upon estrogen administration, reaching a maximal receptor concentration of 1.4-1.6 pmol/mg cytosol protein within 7 days. Protein blot analysis using a monoclonal antibody (hPRa 1) raised against PR from EnCa 101 showed no immunoreactivity in tumors grown in the absence of estrogen. Immunoreactive proteins of mol wt 116,000 and 81,000 were detectable 8 h after estrogen administration and increased in intensity as the cytosolic PR concentration increased. Interestingly, the protein of mol wt 116,000 was composed of mol wt isoforms and was detectable as a doublet 8 h after estrogen administration and finally as a triplet. The effect of estrogen withdrawal on EnCa 101 PR concentration and structure was determined by removal of 17 beta-estradiol pellets (200 pg/ml plasma) from EnCa 101-bearing animals after achievement of maximal tumor PR concentrations. The PR concentration in tumor cytosols decreased in a biphasic manner after estrogen removal, with the initial rapid phase having a half-life of around 2 days. Cytosolic PR was still detectable 21 days after estrogen withdrawal. Protein blot analysis showed that immunoreactive proteins of mol wt 116,000 and 81,000 were also detectable up to that time. Photoaffinity labeling with [3H]R5020 demonstrated that the 81,000 mol wt protein, as well as each of the triplet proteins at mol wt 116,000, was specifically photoaffinity labeled. The 116,000-mol wt protein was detected as a triplet on protein blots until 13 days after estrogen withdrawal, when diminution in the intensity of the highest mol wt triplet protein was noted.
Clarke
C L
CL
Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Feil
P D
PD
Satyaswaroop
P G
PG
D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004343:Drug Implants; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D011980:Receptors, Progesterone / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D004343:Drug Implants; D011980:Receptors, Progesterone; D004958:Estradiol