Estradiol-17 beta and progesterone regulate secretion of uteroglobin through different pathways

Uteroglobin, the primary secretory protein of rabbit uterine epithelium, was localized by the direct immunoperoxidase method in uteri of control ovariectomized rabbits and of ovariectomized rabbits injected with progesterone or estradiol-17 beta. In control rabbits, staining for uteroglobin was almost entirely abolished six weeks after bilateral ovariectomy. Two days following progesterone injection of ovariectomized rabbits, intense staining for uteroglobin could be detected within the endoplasmic reticulum, Golgi complexes, and compact secretory vesicles of most endometrial epithelial cells. Estradiol-17 beta injection resulted in a different intracellular pattern of uteroglobin distribution. Two days following treatment with that steroid hormone, intense staining for uteroglobin was localized within large apical mucous droplets and moderate staining was present in the endoplasmic reticulum and Golgi complexes of these cells. The increased mucin content of the endometrial epithelium following treatment with estradiol-17 beta was confirmed by a periodic acid-Schiff histochemical reaction in the presence of diastase. Quantitation by radioimmunoassay of uteroglobin production in vitro by uterine fragment confirmed that progesterone had a greater effect on enhancing uteroglobin production than estradiol-17 beta and that both steroid hormones did not have any effect after 30 min of incubation in vitro. We suggest that progesterone not only regulates uteroglobin production at the transcriptional level, but that it also regulates the mode of uteroglobin secretion by the induction of a different pathway, compared with the one used when estradiol-17 beta is administered alone.