IMMUNOHISTOCHEMICAL LOCALIZATION OF ESTRADIOL AND PROGESTERONE RECEPTORS IN HUMAN UTERUS THROUGHOUT PREGNANCY - EXPRESSION IN ENDOMETRIAL BLOOD-VESSELS

Although progesterone and estrogens are essential to maintain human pr egnancy after implantation, the localization of their specific recepto rs in different uterine cell types during pregnancy has not been inves tigated. We studied uteri (n = 40) obtained during the first 3 months of pregnancy (n = 21) and in late pregnancy (n = 9) as well as from wo men 5-14 weeks pregnant (n = 10) who had received the antiprogestagen RU 38486 (Roussel-UCLAF) to induce cervical dilation. Frozen tissues w ere processed for indirect immunocytochemical staining with specific m onoclonal antibodies against estrogen receptors (ER; Abbott Laboratori es) and progesterone receptors (PR; Li 417). Specific staining for ste roid receptors was only detected in the nucleus. In the endometrium, P R staining remained fairly constant throughout pregnancy, whereas ER s taining was initially weak and then undetectable. PR was widely expres sed in stromal cells and in spiral arterial wall cells, whereas ER was expressed in scattered stromal cells and arterial cells. Both PR and ER were absent from glandular epithelium, contrasting with the secreto ry activity during the first trimester. Spiral arteries of the endomet rium and myometrial smooth muscle cells showed intense PR and moderate ER staining in early pregnancy. The progesterone antagonist RU 38486 (mifepristone), given in early pregnancy at a dose of 200 mg, caused a marked increase in ER staining and a smaller increase in PR staining in stromal cells, whereas the glandular epithelium remained negative f or both ER and PR (except for one and two specimens, respectively).We conclude the following. 1) Stromal cells retain PR despite the high pr ogesterone levels during pregnancy, in keeping with the role of proges terone in stromal decidualization. The absence of PR from the secretor y glandular epithelium suggests a paracrine link between decidualized stromal cells and epithelial cells. 2) Significant PR downregulation b y progesterone during pregnancy occurs only in epithelial cells of the endometrium. 3) In contrast, the absence or low level of ER staining in the various cell types of the endometrium during gestation concurs with the known effect (down-regulation) of steroid hormones on ER mRNA or protein levels. The increase in ER in human decidua after RU 38486 treatment indicates that the main cause of the low ER levels is proge sterone secretion. 4) The intense PR staining in smooth muscle cells o f spiral arteries during early pregnancy suggests that progesterone is essential for modulating blood flow during pregnancy.