Progesterone and estrogen control of the response of rat uterine lysosomal cathepsin D activity to a deciduogenic stimulus.

Endometrial sensitization to deciduogenic stimuli and destruction of luminal epithelial cells during the uterine decidual reaction may depend upon the control of endometrial lysosome function by progesterone and estradiol. These experiments examined progesterone and estrogen control of the levels of uterine cathepsin D and the response of cathepsin D activity to a deciduogenic stimulus. The progestin medroxyprogesterone acetate increased rates of uterine cathepsin D synthesis, but these rates were not enhanced by estradiol pretreatment. The response of cathepsin D activity to a deciduogenic stimulus, however, required progestin pretreatment, followed by estrogen treatment. Decreases in cathepsin D activity after a deciduogenic stimulus required estrogen stimulation for approximately 12 h, and this estrogen effect could be suppressed by treatment with dexamethasone or inhibitors of prostanoid synthesis. These results indicate that destruction of luminal epithelial cells during the uterine decidual reaction involves the coordinated control of the cathepsin D content by progesterone and of intracellular lysosome activity by estradiol.