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Structural studies, localization in tissue and clinical aspects of human endometrial proteins
M Seppälä1, L Riittinen, M Julkunen
1Department I of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland.
Insights
Human endometrial proteins PP12 and PP14, abundant in amniotic fluid, show sequence homology to proteins binding small molecules. Their levels correlate with endometrial changes and pregnancy, suggesting roles in IGF metabolism and fetal growth.
Area of Science:
- Reproductive biology and protein biochemistry.
- Analysis of human endometrial proteins and their functions.
Background:
- PP12 and PP14 are human endometrial proteins found in amniotic fluid.
- PP12 binds Insulin-like Growth Factor I (IGF-I).
- PP14 shares sequence homology with beta-lactoglobulin and retinol-binding protein.
Purpose of the Study:
- To characterize the human endometrial proteins PP12 and PP14.
- To investigate the sequence homology and potential functions of PP14.
- To explore the clinical significance of PP12/IGF-bp and PP14 levels in various physiological and pathological conditions.
Main Methods:
- Purification of PP12 and PP14 from human amniotic fluid.
- SDS-PAGE and N-terminal amino acid sequencing.
- Sequence homology analysis using bioinformatics tools.
- Clinical correlation studies of protein levels in serum and tissue.
Main Results:
- Purified PP12 showed multiple immunoreactive bands with a common N-terminal sequence, binding IGF-I.
- PP14 exhibited sequence identity with beta-lactoglobulins, human retinol-binding protein, frog protein BG, and insecticyanin.
- PP12/IGF-bp and PP14 levels increased with endometrial secretory changes.
- Elevated PP12/IGF-bp was observed in hyperstimulated cycles, pregnancy, pre-eclampsia, and certain cancers.
- PP14 levels correlated with endometrial secretory function and luteal phase progression.
Conclusions:
- PP14 belongs to a protein family involved in binding and transporting small molecules.
- PP12/IGF-bp is linked to IGF metabolism and fetal growth.
- PP14 serves as a marker for endometrial secretory function.
Abstract:
Two human endometrial proteins, PP12 and PP14, are abundant in human amniotic fluid which is an excellent source for purification. In SDS-PAGE, purified PP12 migrates as several immunoreactive bands from 17,000 to 34,000, all having the same N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-, and all of them binding IFG-I. PP14 migrates at 28,000, and its N-terminal sequence is Met-Asp-Ile-Pro-Gln-Thr-Lys-Gln-Asp-Leu-Gln-Leu-Pro-Lys-Leu-Ala-Gly-Thr- Trp-His-Ser-Met-. There is a 59% identity between this sequence and that of horse beta-lactoglobulin, and also between PP14 and beta-lactoglobulins of various other species. PP14 and human retinol-binding protein show a 23% sequence identity, and the amino acid residues -Gly-Thr-Trp- at positions 17-19 of PP14 are identical with the corresponding residues of human retinol-binding protein. This site is assumed to play a part in the binding of retinol. An additional sequence identity (32%) is reported here for PP14 and protein BG, a 182 amino acid protein deduced from a 700-base pair cDNA clone isolated from the olfactory neuroepithelium of the frog. Sequence homology is also reported here between PP14 and insecticyanin, a camouflage-associated biliprotein in insects. The sequence of PP14 is therefore homologous to members of a family of proteins that bind and transport biologically active small molecules. Clinical studies have indicated an increase of PP12/IGF-bp and PP14 in the endometrium with advancing secretory changes. PP12/IGF-bp is also found in preovulatory follicular fluid. In hyperstimulated cycles of infertile women undergoing in-vitro fertilization, the serum PP12/IGF-bp concentration rises as multiple follicles mature, and luteinized granulosa cells contain this protein. In non-pregnant women, elevated values have been found in patients with advanced ovarian cancer and primary liver cancer. During pregnancy the serum PP12/IGF-bp concentration rises above the level in non-pregnant women around Week 8 of gestation. Abnormally high levels are seen in patients with pre-eclampsia and, in the third trimester, there is an inverse correlation between the maternal serum PP12/IGF-bp level and fetal weight. From these studies it is likely that a relationship exists between PP12/IGF-bp, the metabolism of IGFs and fetal growth. In non-pregnant women, serum PP14 concentrations appear to reflect endometrial secretory function. This is indicated by cyclic changes in the PP14 concentration in endometrial tissue and by the rising PP14 values in the late luteal phase.(ABSTRACT TRUNCATED AT 400 WORDS)