The Role of Membrane Progesterone Receptor Associated Proteins in Gynecological and Reproductive Disorders, And Cancers: An Editor’s Historical Perspective
Part 2: Clinical benefits of P supplementation post-ovulation
Jerome H Check* and Naomi S Ganpo-Nkwenkwa
ABSTRACT
There is evidence that the development of spiral arteries from early luteal phase to the end of pregnancy are predominately formed not from neovascularization but through autoimmune stripping off of the thick walls on uterine arteries. These spiral arteries require a cell wall only 1 cell thick to allow nutrient exchange between mother and fetus. The invasion of cellular immune cells with 70% natural killer (NK) cells is facilitated by the effect of progesterone (P) in blocking dopamine to allow increased cellular permeability allowing infusion of irritants into pelvic tissue causing an inflammatory effect. These cellular immune cells do permeate the fetal placental microenvironment. Thus, they need to be subsequently suppressed, or they will attack the fetal semi-allograft. One mechanism used to suppress these NK cells, macrophages, and cytotoxic T-cells is by P activating membrane progesterone receptors (mPRs) to make certain immunomodulatory proteins e.g., the progesterone induced blocking factor (PIBF) which, in turn, will abrogate the killing action of these cellular immune cells. Thus, supplementing the luteal phase with extra P may correct infertility, and prevent recurrent miscarriage, or preterm delivery. Sometimes if adding P is insufficient to fully negate the killing action of these cellular immune cells, one could treat the patient with a dopamine agonist to try to reduce excessive permeability leading to excessive inflammation.
