HORMONAL REGULATION OF ENDOMETRIAL DIFFERENTIATION

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The concept of stem cell mediated differentiation that explains the process of tissue regenerations is proposed as a model for the cyclic renewal of human endometrium. Regulation of endometrial function by steroid hormones which forms the major part of the proposed scheme will be examined in the initial phase of the study. Accordingly, the cellular distribution of hormone-sensitive markers, such as receptors for estradiol and progesterone and estradiol-17Beta and 20Alpha-dihydro-progesterone dehydrogenase activities, within the glands and stroma, their alterations within these cell populations during the menstrual cycle, modulation of endometrial functional differentiation, in vitro, and the temporal sequence of steroid-receptor interactions will investigated. Several predictions of the scheme in regard to growth characteristics of epithelial cells and biochemical differentiation mediated by sex steroids will be followed in organ and cell culture system. Modulation of these steroid effects with inhibitors (12-0-tetradeconoyl phorbol acetate) and promotors (retinoids) of differentiation will serve to validate certain parts of the proposed scheme. Various inhibitors of transcription and translation will be utilized to indirectly demonstrate that steroid-mediated differentiation is indeed due to gene transcription. Simultaneous correlation of the biochemical end-points with the well established morphologic differentiation will help to identify the differentiation stages.