Progesterone-regulated changes in transcriptional events in rabbit uterus

Abstract

The role of steroid receptors in the early events of progesterone action was elucidated by examining the temporal relationship between the nuclear accumulation of progestin receptor and changes in activities of RNA polymerases I and II, as well as that of chromatin template in rabbit uterus. Following a 5-day estrogen pretreatment, the animals received an intravenous injection of progesterone (10 mg), after which they were killed at timed intervals. Nuclear progestin receptor level, as measured by an exchange assay, reached the peak value 30 min after hormone administration (11 600 to 46 600 sites/nucleus) and declined to the control levels by 4 h. Changes in the activities of RNA polymerases I and II did not follow identical time courses: polymerase I rose at 30 min and remained elevated for 2 h and then declined to about 75% of the pretreatment activity, whereas RNA polymerase II activity increased more rapidly (at 15 min), and was followed by a sharp decrease to about 50% of the initial value. Thereafter, the latter enzyme activity rose slowly and reached the pretreatment level within 12 h of progesterone administration. Early changes in chromatin template activity were similar to those in RNA polymerase I with a second rise by 8–10 h. The early inhibition of transcriptional events by progesterone may result from antiestrogenic properties of this steroid. Accumulation of nuclear progestin receptor occurs at a similar time to early changes in the transcriptional events suggesting a regulatory role for the hormone receptor complexes.