Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF)

J Assist Reprod Genet. 2016 Feb;33(2):221-9. doi: 10.1007/s10815-015-0619-7. Epub 2015 Dec 3.

Abstract

Purpose: To determine if exposure to progesterone alone is sufficient to increase the production of the immunomodulatory protein known as the progesterone induced blocking factor (PIBF). Also to determine what method of progesterone delivery or form of P best stimulates PIBF secretion.

Methods: Serum samples from patients with infertility and paid volunteers were evaluated for both PIBF and progesterone at various times during the follicular phase and the luteal phase in both natural cycles and cycles involving embryo transfer after endogenous and exogenous progesterone exposure and after various synthetic progestins. PIBF was measured by a non-commercial research ELISA assay. Comparisons were made of serum PIBF before and after exposure to progesterone, 17-hydroxyprogesterone, and oral contraceptives. PIBF was also measured before and after transfer of embryos.

Results: Progesterone alone without exposure to the fetal allogeneic stimulus was able to produce a marked increase in serum PIBF. Neither a synthetic progestin (19-nortestosterone derivative) nor 17-hydroxyprogesterone caused an increase in PIBF. Some PIBF is generally detected even in the follicular phase.

Conclusions: A previous concept considered that an allogeneic stimulus, e.g., from the fetal semi-allograft, was necessary to induce de novo progesterone receptors in gamma delta T cells, which, in turn, when exposed to a high concentration of progesterone, would secrete high levels of PIBF. These data show that exposure to an allogeneic stimulus is not needed to cause a marked rise in PIBF, merely progesterone alone is sufficient.

Keywords: Fetal semi-allograft; Immunomodulatory protein; Natural killer cells; Progesterone; Progesterone induced blocking factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-alpha-Hydroxyprogesterone / administration & dosage
  • Adult
  • Allografts
  • Contraceptives, Oral / administration & dosage
  • Embryo Transfer*
  • Female
  • Fertilization in Vitro*
  • Humans
  • Immunomodulation / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Male
  • Middle Aged
  • Pregnancy
  • Pregnancy Proteins / blood*
  • Progesterone / administration & dosage
  • Progesterone / blood*
  • Suppressor Factors, Immunologic / blood*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Contraceptives, Oral
  • PIBF1 protein, human
  • Pregnancy Proteins
  • Suppressor Factors, Immunologic
  • Progesterone
  • 17-alpha-Hydroxyprogesterone