Dynamics and control of progesterone receptor synthesis in the fetal uterus of the guinea-pig in organ culture.

Progesterone receptor concentrations increased in fetal guinea-pig uterus in organ culture to as high as 13 X 15 +/- 1 X 22 pmol/mg DNA without any added steroid, although cytosol and nuclear oestrogen receptor levels were very low (0 X 41-1 X 92 pmol/mg DNA). Even after a 3-day exposure to 5 X 10(-8) M-progesterone, which inhibits its own receptor (1 X 14 +/- 0 X 31 pmol/mg DNA), progesterone receptor levels rose to 8 X 58 +/- 1 X 39 pmol/mg DNA when progesterone was removed. This replenishment was inhibited by progesterone and 5 alpha-dihydroprogesterone but was not affected by oestradiol, tamoxifen or dexamethasone. The incorporation of [3H]thymidine into nucleic acids was not decreased by progesterone so that its inhibition of its own receptor in the explants was not due to an inhibition of cell replication. Fetal uterine explants from oestrogen-primed fetuses, after an initial decrease in progesterone receptor, also showed a rise to 7 pmol/mg DNA on day 2 which could be decreased by exposure to progesterone and replenished by removal of this hormone (6-8 pmol/mg DNA), the entire process occurring without apparent oestrogen stimulation. Progesterone rather than oestradiol appears to be a key regulator of progesterone receptor synthesis in the fetal guinea-pig uterus, although oestradiol, along with other factors, may also be involved.