Progesterone receptor subtype B is differentially regulated in human endometrial stroma

Two anti-progesterone receptor (PgR) antibodies, a new one specific to PgR(B), the other to PgR subtypes A + B, have been used to examine the cellular location of PgR subtypes A and B in normal endometrium throughout the menstrual cycle and in early human decidua by standard immunohistochemical techniques. PgR(A+B) is the receptor detected by the antibody recognizing both isoforms of the receptor. PgR(B) is the receptor detected by the new antibody specific to the B isoform. Since it is not possible to raise antibody specific to PgR subtype A, all immunohistochemical analysis of the PgR(A) subtype is by subtractive inference. Thus we refer to PgR(A) as the subtype responsible for positive immunoreactivity when the PgR(B) subtype cannot be specifically detected. Endometrial biopsies were collected from 40 women with regular menses (n = 5 each stage of cycle: menstrual; early, mid and late proliferative; ovulatory; early, mid, and late secretory). Decidual tissue was obtained from 10 women undergoing first trimester surgical termination of pregnancy. As previously reported, the PgR(A+B) antibody stained glandular and stromal nuclei during the proliferative phase but only stromal nuclei during the secretory phase and early pregnancy. The new PgR(B) antibody also stained both cell types intensely during the proliferative phase, but failed to stain either stromal or glandular nuclei strongly during the secretory phase and early pregnancy. We concluded that, while both PgR subtypes were present in glands and stroma in the proliferative phase, and both subtypes were dramatically reduced in the glands during the secretory phase, PgR(A) remained as the predominant type in the stroma during the secretory phase and early pregnancy. The profound effects of progesterone on endometrium during the secretory phase and early pregnancy appear to be mediated primarily by PgR(A) in the stroma.