Cell and Molecular Biology of the Uterus

Sharad G. Joshi, Joshi, Sharad G.

Progesterone (P), which is the major secretory product of the corpus luteum (CL) is the key hormone of pregnancy. CL defects that cause P to be secreted for too brief a period or at too low a rate are associated with an underdeveloped or inadequate endometrium which is incapable of supporting pregnancy. Some investigators, therefore, have recommended the use of exogenous P support in chronic CL defect patients who wish to conceive. However, the mechanisms by which P regulates endometrial function are poorly understood and there is no suitable, non-invasive method to monitor in individual patients the endometrial response to either endogenous or exogenous progesterone. We therefore initiated a search for progesterone-dependent endometrial protein(s) which might serve as a marker to assess effects of progestin therapy on endometrial function, and which might also afford insight into the mechanism of P action. We have detected a hormone-dependent endometrial protein designated "progestagen-associated (or -dependent) endometrial protein" or PEP. PEP is a glycoprotein (molecular weight approximately 47,000) which is synthesized in the endometrial glands and secreted into the blood. Its synthesis increases dramatically during pregnancy, as indicated by a more than 1000-fold greater PEP concentration in the decidua. PEP is not synthesized by the immature placenta, but binds to placental cell membranes. In normally cycling women, the serum PEP concentration increases in an exponential manner during the late luteal phase. In cycling infertile women, a direct relationship was found to exist between serum PEP levels they attained in the late luteal phase and their endometrial development, the serum levels being subnormal in women with inadequate endometrium. Menstrual cycles that are anovulatory or with a CL-defect are associated with low luteal phase serum PEP levels. In both pre- and post-menopausal women, serum PEP levels increase following a progestin challenge, demonstrating that PEP is indeed a progestin-dependent protein. Very low luteal phase serum PEP levels are encountered in some women who do not conceive following in vitro fertilization and embryo transfer (IVF/EF), suggesting that endometrial inadequacy is a major cause of failure in this procedure. In patients who undergo ovarian stimulation by exogenous hormones but do not conceive following IVF/ET, luteal phase serum PEP levels are markedly higher in those who receive luteal phase P support than those with no support.(ABSTRACT TRUNCATED AT 400 WORDS)