The bulk of information that has contributed to our understanding of mechanism of progesterone action originates from avian models. During recent years rabbit uteroglobin has been successfully utilized as a model to exploit progestin action in mammalian tissues, too. Previous studies in our laboratory have yielded many interesting features in the regulation of uteroglobin gene activity and its relation to progesterone receptor dynamics, such as inhibition (and potentiation) of progesterone action by simultaneously administered estradiol or tamoxifen; progesterone receptor consumption during progesterone action; multihormonal control of uteroglobin synthesis, and dissociation of receptor changes from the biologic response. The present proposal is a continuation of these studies and utilizes uteroglobin and its mRNA (measured by RIA and cDNA hybridization, respectively) as biological markers for progestin action. To ensure that the regulatory events studied are not peculiar to uteroglobin, other progesterone-induced uterine proteins are concomitantly evaluated. Since uteroglobin is under multihormonal control--progestins, androgens, and estrogens regulate uteroglobin synthesis--this model offers an excellent system for studies of steroidal interactions in the regulation of a specific endometrial gene product. One of the major specific aims is to clarify the mechanism of antiprogesterone action of estradiol in the uterus. Steroid action is mediated via cytosol receptor proteins, but the extent to which biological responsiveness, maintenance and termination of steroid action are related to receptor dynamics are poorly understood. In the case of progesterone, receptor consumption (disappearance of steroid binding site) during hormone action still complicates the above relationships. The second specific aim of this proposal is devoted to clarification of these issues with a special emphasis on progesterone receptor consumption its biological significance. It may well be that an ultimate answer cannot be achieved utilizing current receptor assay techniques based on the use of labeled steroids, and hence progesterone receptors will be purified, characterized, and an immunologic assay for their measurement will eventually be set up.
| Huang, J R; Tseng, L; Bischof, P et al. (1987) Regulation of prolactin production by progestin, estrogen, and relaxin in human endometrial stromal cells. Endocrinology 121:2011-7 |
