Endocrinology, Vol 118, 2488-2494, Copyright © 1986 by Endocrine Society

ARTICLES

Progesterone receptor replenishment during sustained progesterone treatment in the hamster uterus

WC Okulicz

Previous studies have demonstrated that uterine progesterone (P) receptor is under dual hormonal control; estradiol (E2) induces the synthesis of cytosolic P receptor, and P induces the loss of its own receptor and antagonizes E2-induced P receptor replenishment. The objective of this study was to examine the contributions of E2 and P in the replenishment of uterine P receptor during sustained P exposure. Silastic implants of varying length (0.4, 0.8, 1.5, 2.5, and 5.0 cm) were packed with crystalline P and placed sc in the flank region of ovariectomized adult female hamsters. The serum P levels obtained with these implants (2-22 ng/ml) were within the physiological range observed previously during the estrous cycle, pregnancy, and lactation in the Syrian hamster. Control animals received a blank implant (1.5 cm). Three, 5, and 7 days after placement of the implants, uterine cytosolic and nuclear P receptor levels were decreased as serum P level was increased by the P implants. Total cellular P receptor level was inversely correlated with serum P level at 3 days (r = -0.996), 5 days (r = -0.98), and 7 days (r = -0.99). To distinguish the effect of E2 and P, ovariectomized animals were maintained on Silastic implants of P (1.5 cm) or P plus E2 (1.0 cm). After 3 days, cytosolic P receptor was determined 0, 8, 16, 24, and 48 h after removal of P implants. No difference was observed in cytosolic P receptor between P and P plus E2 groups before P withdrawal. E2-maintained animals showed a significant rise of cytosolic P receptor at all time points after P withdrawal. Although P withdrawal in the absence of E2 showed no significant change in P receptor at 8 or 16 h, a significant increase in P receptor (equivalent to that of ovariectomized control animals) was observed at 24 and 48 h. Treatment of ovariectomized animals with cycloheximide significantly reduced uterine cytosolic P receptor levels 8, 18, and 24 h after treatment. These results suggest that 1) an active receptor replenishment process occurs in the absence of E2; 2) this replenishment process does not appear to be P dependent, but, rather, constitutively expressed; and 3) the rate of constitutive P receptor replenishment is slower and of lower magnitude than that promoted by E2. Because P antagonizes E2-induced P receptor, a constitutive P receptor replenishment mechanism may play an important role in the maintenance of P action during sustained P exposure, such as in pregnancy.