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Progestin-Dependent Human Endometrial Protein: A Marker for Monitoring Human Endometrial Function

  • Sharad G. Joshi
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 230)

Abstract

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~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. In women in whom implantation occurs following IVF/ET, serum PEP levels increase sharply as early as day 5 post-oocyte aspiration and with a doubling time of 2.49+1.71 (Mean +SE) days. PEP levels peak within 4 weeks of conception. The levels remain more or less steady during 10–12 weeks post conception and rapidly decline thereafter. PEP was also detected in the peritoneal fluid (PF) of women. In women with moderate to severe endometriosis, PEP concentration in PF is 10-fold higher than in those women with mild endometriosis or control subjects. In some patients with primary endometrial cancer, the treatment with a progestin results in a significant change in the PEP concentration in the endometrial tumor and/or serum. From these studies, we conclude that progestin-stimulated human endometrium synthesizes a specific protein, namely PEP. Although the role of PEP in pregnancy is totally unknown, determinations of PEP in serum or PF offers a practical means to assess endometrial responses to endogenous and exogenous progesterone and progestins in infertile women, habitual aborters, endometriosis patients and patients with endometrial hyperplasias or neo-plasias. This method is minimally invasive, quantitative, and simple enough to be used on a repetitive basis in large scale clinical trials.

Keywords

Endometrial Cancer Luteal Phase Corpus Luteum Endometrial Cancer Patient Late Luteal Phase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Sharad G. Joshi
    • 1
  1. 1.Department of Obstetrics and Gynecology, and BiochemistryAlbany Medical CollegeAlbanyUSA

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