107. Progestin-dependent proteins in the human endometrium

The Progestational Endometrium

“…It is still the major secretory product of the decidua at 6 weeks of gestation but not at 12 weeks. This pattern, the immunocytochemical local ization of PEP and AUP to the glandular epithelium in secretory endometrium, 106,113 and the association of α 2 -PEG with the spongiosa, the deeper layer of the decidua, 46 indicate that α 2 -PEG may be synthesized by glandular epithelial cells. In contrast, α 1 -PEG is only a minor product of endometrium obtained dur ing nonpregnant cycles, but, by 12 to 15 weeks of gestation, it has become the major protein secreted by the decidua.…”

“…Several studies have concluded that human uterine fluid is essentially a filtrate of plasma [102][103][104] and that, during the early and midluteal phase of the cycle, it contains only low levels of fibrinolytic activity. 105,106 McRae 107 has reviewed the role of the blood-uterine barrier (tight junctions between endometrial epithelial cells) in regulating the composition of the uterine fluid in a variety of species and has suggested that proteins that are blood borne or synthesized by the stroma may be selectively transported across the endometrial epithelium by a unidirectional transcellular pathway. This would provide a mechanism for altering the electrolyte and protein composition of the uterine fluid and would account for the higher concentrations of progesterone, a more lipid-soluble steroid relative to estradiol.…”

“…α 2 -PEG, which is similar to pro gesterone-dependent endometrial protein (PEP) and α-uterine protein (AUP), is also a major secretory product of the progesterone-dominated endome trium during the luteal phase. 46,106,110,112,113 The synthesis of this dimeric glycoprotein increases from about day 18 onward (just prior to implantation) dur ing the normal cycle and continues throughout early pregnancy. It is still the major secretory product of the decidua at 6 weeks of gestation but not at 12 weeks.…”

“…119 Analysis of the N-terminal amino acids of PPM indicates signifi cant sequence homology with β-lactoglobulin, a ma jor component of bovine milk whey, which in turn is similar to human serum retinol-binding protein. 118 Several other proteins produced by the endome trium or decidua also accumulate in the amniotic fluid during pregnancy; examples include α-l,4-glucosidase, heat-labile alkaline phosphatase, diamine oxidase, 106 and decidual prolactin. 78,120 Decidual prolactin (dPRL) was one of the first human endome trial proteins to be identified because it could be detected with the radioimmunoassay used to meas ure pituitary prolactin.…”

“…46,131 The local accumula tion or in situ production of protease inhibitors such as α 2 -macroglobulin, α 1 -antitrypsin, inhibitors of plasminogen activator, and possibly PAPP-A could constitute an important protective function during implantation and early placentation when extracellu lar levels of fibrinolytic enzymes are probably ele vated in the endometrium, especially in the vicinity of the invading trophoblast. 106 The endometrium or decidua may also release a number of conventional paracrine hormones such as relaxin, [135][136][137] renin-an giotensin 138,139 and opioid peptides. [140][141] In addi tion to this assortment of protein products, the pro gestational endometrium also appears to be capable of metabolizing steroids to produce more potent or bioactive forms, e.g., conversion of androgens to estrogens, [142][143][144] cortisone to Cortisol, 145 and cholecalciferol to the active form of vitamin D. 146,147 Fi nally, the endometrium is a rich source of a variety of prostaglandins that are likely to be involved in mod ulating such critical events as decidualization, vascu lar permeability, vasodilation, vasoconstriction, and myometrial contractions.…”