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PubMed1995

Serum levels of hPL, PAPP-A and PP14 in patients with early pregnancy bleeding and subchorionic hemorrhage.

OBJECTIVE: To investigate possible endocrine changes in patients with early pregnancy bleeding and subchorionic hemorrhage. DESIGN: Prospective study in first trimester of pregnancy comparing circulating levels of human placental lactogen (hPL), pregnancy-associated plasma protein A (PAPP-A) and endometrial secretory protein PP14 (PP14) in women with and without subchorionic hemorrhage. SUBJECTS: Sixty-nine women with early pregnancy bleeding, who in week 7-14 had a blood sample and an ultrasound study with both determination of fetal crown-rump length and a search for subchorionic hemorrhage. RESULTS: There was no difference between serum levels of hPL, PAPP-A and PP14 in 29 women with and 40 women without subchorionic hemorrhage, and no correlation between serum levels and the size of the hematoma. CONCLUSION: Judged from the serum levels of the studied substances there were no indications of an impaired function of the trophoblast or the decidua that could explain the development of subchorionic hemorrhage.

Adult↗
PubMed1996

Endometrial and fetoplacental markers in pregnancies with fetal congenital nephrosis.

OBJECTIVE: Congenital nephrotic syndrome of the Finnish type [CNF] is an autosomal recessive disorder leading to death in early childhood, if treated conservatively without early renal transplantation. Prenatal screening at midtrimester is feasible by measuring maternal serum alpha-fetoprotein [MSAFP], elevated amniotic fluid [AF] AFP being the only diagnostic test in population screening. We studied whether concentrations of other pregnancy-related markers offer any ancillary procedure for screening. METHODS: In a prospective case-control study, the concentrations of maternal serum human chorionic gonadotropin [hCG], unconjugated estriol [uE3], human placental lactogen [hPL] and placental protein 14 [pp14] were measured in samples from six singleton pregnancies associated with fetal CNF and from 18 matched controls at 15 weeks of gestation. RESULTS: In the CNF group, mean hCG and pp 14 concentrations were slightly elevated, whereas uE3 and hPL concentrations were within the lower normal range. None of these differences were statistically significant and the distribution of these values was too wide to use them for screening. CONCLUSIONS: Low unconjugated E3 and elevated hCG concentrations were expected, since newborns with CNF are growth-retarded and have large placentas. The extent of these alterations was not sufficient to identify high risk pregnancies. Substantial differences in the maternal serum concentrations of hPL and pp 14 were not observed. Hence, MSAFP screening at midtrimester is the strategy of choice for prenatal detection of CNF.

Amniotic Fluid↗
PubMed1993

Changes in levels of IgM RF and alpha 2 PAG correlate with increased disease activity in rheumatoid arthritis during the puerperium.

In this prospective study of 24 pregnant patients with rheumatoid arthritis, quiescent disease activity in 21 patients (88%) during gestation was followed by more active disease in the puerperium in 19 patients (79%). Increased disease activity was reflected in a deterioration in manual dexterity and this was found to correlate with a post-partum rise in IgM rheumatoid factor (IgM RF) (r = 0.86) and a post-partum decline in pregnancy associated alpha-2 glycoprotein (PAG) (r = 0.44). The increase in IgM RF also correlated with increased disease activity measured by a visual analogue scale (r = 0.44). Changes in IgA RF were not observed. These results suggest that PAG and IgM RF could contribute to the modulation and pathogenesis of rheumatoid arthritis during pregnancy.

Adult↗
PubMed1989

The measurement of secretory endometrial protein PP14 in serum from postmenopausal women receiving unopposed estrogen or continuously combined estrogen/progestogen.

A highly sensitive radioimmunoassay was developed to measure the low serum concentrations of the endometrial secretory placenta protein 14 (PP14) in postmenopausal women. The assay was established by selecting optimum reaction conditions for radioactive labelling of PP14, combined with simple procedures for the purification of the labelled PP14. The PP14 assay was used in 2 groups of healthy, early postmenopausal women blindly receiving either estrogen monotherapy (n = 20, placebo n = 25) or continuously combined estrogen/progestogen therapy (n = 20, placebo n = 23). Neither of these regimens is believed to produce secretory endometrium. During the 12 months of estrogen monotherapy, serum PP14 (S-PP14) remained unchanged at 4.9 micrograms/l, when compared with placebo. Treatment with continuously combined estrogen/progestogen showed a small but significant increase in S-PP14 from 5.3 micrograms/l to 7.2 micrograms/l at 3 months. S-PP14 remained at this slightly elevated level throughout the treatment period of 24 months. Three months after hormone withdrawal, S-PP14 had returned to the pretreatment level. We suggest that S-PP14 might be a useful marker of secretory endometrium.

Drug Combinations↗
PubMed1997

Placental protein 14 (PP14) does not predict endometrial status under hormone replacement therapy.

Our objective was to compare serum level of placental protein 14 (PP14) with histological findings in endometrial evaluation of postmenopausal women using hormone replacement therapy (HRT). In a subset of 109 out of 140 women included in a randomized comparative study, serum levels of PP14 were determined after 12 months of use of (1) no HRT; (2) oral micronized 17 beta-estradiol/oral sequential dydrogesterone; (3) transdermal 17 beta-estradiol/oral sequential dydrogesterone; or (4) oral tibolone. Subjects underwent Pipelle biopsy after 12 months. The serum level of PP14 was determined by sandwich enzyme immunoassay (ELISA). The two-tailed t-test and one-way ANOVA or their non-parametric equivalents were used to test for statistical significance. All three HRT regimens were safe with respect to the endometrium. Hyperplastic or malignant changes were not observed. There was a significant difference in the mean values of PP14 between the groups of inactive/atrophic and secretory endometrium (p < 0.01). However, there was a wide range of individual values for PP14 within the groups and a wide overlap in values between the groups of non- substituted and hysterectomized women. The quantitative determination of PP14 in the serum did not provide supplementary information on the substituted endometrium. From this study it can be concluded that the serum PP14 determination is not useful to predict endometrial status under HRT. The relatively high levels of PP14 in hysterectomized patients suggest ectopic production.

Biopsy↗
PubMed1998

Placental protein 14 and pregnancy-specific beta 1-glycoprotein in women with suppressed, normal and stimulated follicular maturation.

Not only the ovarian steroids but a number of proteins have an effect on the endometrium and its capability to accept an implanting embryo and to establish a pregnancy. In this study we have selected the placental protein 14 (PP14) which is, in spite of its name, produced by the glandular epithelium of the endometrium. Pregnancy-specific beta 1-glycoprotein (SP1) was also investigated. This marker is trophoblast-specific but it has been chosen since some patients repeatedly exhibit weak but detectable serum SP1 when no embryo is present. There seems to be a negative correlation between the chance of obtaining a pregnancy and the occurrence of such abnormal serum SP1 signals; they could originate from the endometrium itself or from another maternal source influencing the endometrium indirectly. The full-cycle time course was determined for these two proteins as well as for estradiol and progesterone. A total of 66 cycles were analyzed, of which 16 were from ovulating volunteers without any hormonal treatment (controls) and 13 were from women taking oral contraceptives. The remaining 37 cycles were from 32 patients undergoing conventional in vitro fertilization (IVF) treatment. Eight pregnancies were achieved in this group during the study period. We found that abnormal positive SP1 signals occurred predominantly in the unsuccessful IVF subgroup, but also in the control groups (with or without contraceptive pills), and this in a cycle-independent manner. PP14, on the other hand, exhibited cyclic patterns in the IVF and ovulating control cycles as did progesterone. However, in seven out of 13 cycles under oral contraception (and suppressed progesterone), a midcycle rise in PP14 was observed. Moreover, midcycle PP14 levels were generally higher in this group when compared to the ovulating controls as well as to the cycles under controlled ovarian stimulation for IVF. This confirms that PP14 is influenced by progesterone but only in an indirect way or under the additional effect of other hormones. It is unlikely that SP1 plays this role since it was not correlated to any of the other proteins or steroids studied. Nevertheless, SP1 did not occur randomly over the different groups.

Adult↗
PubMed2002

Focal localization of placental protein 14 toward sites of TCR engagement.

TCR signal transduction is amplified by the dynamic accumulation of accessory molecules at APC-T cell contact sites, along with the simultaneous exclusion from these sites of negative regulators, such as certain tyrosine phosphatases and large glycosylated proteins. However, given the general nature of the cytoskeleton-driven clustering mechanism underlying molecular segregation events at the APC-T cell interaction site, the possibility exists that negative regulators might similarly be segregated at these sites. Using fluorescence microscopy, we have demonstrated that placental protein 14 (PP14), a direct T cell inhibitor, focuses toward APC-T cell contact sites in conjunction with conjugate formation. We have further established that the function of PP14 is dependent upon its localization to the sites of TCR triggering, where it negatively regulates T cell activation. Thus, PP14 provides an example of a soluble negative T cell regulator whose inhibitory activity is linked to modulation of the APC-T cell contact site, thereby hindering early events triggered by the TCR.

Antigen-Presenting Cells↗
PubMedDate not supplied

Late luteal phase progestogen-dependent endometrial protein levels in women with in-phase biopsies--can low levels predict a subfertile group?

A group of infertile women who had luteal phase defects (LPD), but in whom follicular maturation was deemed normal, were treated with progesterone until the endometrial biopsy was corrected. At the time the corrected biopsy was obtained, serum was taken and the progestogen-dependent endometrial protein (PEP) concentration was determined. Serum PEP concentration in patients who successfully conceived was 102.5 +/- 62.6% units/mL, while PEP concentrations in patients who failed to conceive were 57.9 +/- 34.4% (P = .003). In patients whose PEP value was more than two standard deviations below the corresponding mean control PEP, pregnancy was achieved in 6/17 (35.3%). The conception rate was significantly greater (25/35, 71.4%) in patients with values higher than this. Thus, the PEP concentration in serum may identify a group of patients with persistent LPD despite apparent normalization of the morphology of late secretory phase endometrium, which might explain some cases of cryptic, unexplained infertility.

Biopsy↗
PubMed2004

[Fertility alpha-2-microglobulin expression in the human bulbourethral glands].

Fertility alpha-2-microglobulin (FAMG) was demonstrated in the human bulbourethral glands by the method of indirect immunoperoxidase staining using monoclonal antibodies against FAMG. The product of the immunohistochemical reaction was primary found in the duct cells. Weak immunopositive reaction was observed in single epitheliocytes of the secretory units. FAMG-positive granularity was typically found in the supranuclear cytoplasmic zone, that corresponds to the localization of secretory granules both in the glandulocytes and in the duct cells. These results suggest, that the bulbourethral glands are probably the additional producers of human seminal plasma FAMG.

Bulbourethral Glands↗
PubMed1992

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis.

OBJECTIVE: To investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis. DESIGN: Plasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility. MAIN OUTCOME MEASURE: The presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts. RESULTS: Peritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL. CONCLUSION: Superficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.

Analysis of Variance↗
PubMed1992

Sequential estrogen and progestogen therapy: assessment of progestational effects on the postmenopausal endometrium.

Healthy postmenopausal women were randomly assigned to groups receiving 28-day treatment cycles of estradiol (E2) valerate (2 mg, days 1-21) combined with medroxyprogesterone acetate (10 mg, days 12-21) (N = 18), 17 beta-estradiol (1.5 mg, days 1-24) combined with desogestrel (150 micrograms, days 13-24) (N = 20), or placebo (N = 18). The progestational effects on the endometrium were assessed by histology, uterine bleeding pattern, and biochemical markers of secretion measured in endometrial tissue (E2 and isocitrate dehydrogenase) and serum (placental protein 14). After 2 years of therapy, 24 women in the hormone groups had secretory endometrium and 13 had atrophic endometrium; in the placebo group, the results were one and 15, respectively. Withdrawal bleeding generally started between days 9-12 after the addition of progestogen in the E2-medroxyprogesterone acetate group, and between days 14-17 in the E2-desogestrel group. All three biochemical markers of secretion were increased in each of the hormone-treated groups compared with the placebo group (P less than .01-.001). Serum placental protein 14 was twice as high in the secretory as in the atrophic phase (P less than .01). Isocitrate dehydrogenase, but not E2 dehydrogenase, was also higher in the secretory phase (P less than .05). Only serum placental protein 14 was significantly related to the uterine bleeding pattern (P less than .01). We conclude that serum placental protein 14 reflects both endometrial histology and bleeding pattern and may be a useful marker of progestational effects on the endometrium. The markers of secretion measured in endometrial tissue are not as reliable for endometrial histology or bleeding pattern.

Desogestrel↗
PubMed1992

Uterine factors in infertility.

Uterine factors contributing to infertility include abnormalities in the myometrium and in the endometrium. Recent studies have mainly addressed endometrial factors. Several methods have been developed to evaluate endometrial function, including quantitative histology, electron microscopy, histochemistry and immunohistochemistry, hysteroscopy, measurement of endometrial protein levels in plasma or endometrial washings, and ultrasonography. The relationship between endometrial abnormality and types of infertility has been explored by various investigators, as has endometrial receptivity in women over 40 years of age, with interesting results. Unfortunately, the best treatment for endometrial defect is still unknown. A better understanding of the precise nature of the abnormality should lead to effective treatment.

Age Factors↗
PubMed2004

[Change of the endocrine function of the pancreas in patients with chronic pancreatitis].

There was a study of 19 chronic pancreatitis patients (10 male and 9 female), 11 chronic pancreatitis and pancreatogenic diabetes mellitus patients (8 male and 3 female) and 12 type 2 diabetes mellitus patients (4 male and 8 female) at the age of 30-60 as well as 15 control group subjects at the same age range. The content of the C-peptide and such peptides as INCINE, PAMG-cine and PAMG-tin in the blood serum was subjected to the immunoradiometric assay. It was discovered that there is a trend to the increased C-peptide level in CP patients while the C-peptide level in CP patients with diabetes mellitus was smaller than that in the control group; the C-peptide level in CP patients with type 2 diabetes mellitus was higher as compared to that in the control group. It was shown that erythrocytes of CP patients are less sensitive to insulin action and do not respond to the presence of insulinomimetic peptides under examination during the glucose uptake test. CP patients with diabetes mellitus and type 2 diabetes mellitus patients are more sensitive to the action of insulin and peptides applied. Synthetic insulinomimetic peptides can serve as a means for discovering the functional cell deficiency under the glucose uptake test.

Adult↗
PubMed1990

Serum concentrations of two endometrial proteins are not useful for monitoring postmenopausal estrogen/progesterone therapy.

Measurements of the serum concentrations of the endometrial proteins IGFBP-1 and PP14 were made in an attempt to monitor the adequacy of the P effect in women receiving 1 year of 100 to 200 micrograms of percutaneous E2 for 28 days each month and 10 mg oral MPA given during the last 12 days of E2 administration. There were no significant changes in IGFBP-1 levels; a small, but significant increase in PP14 levels after E2 plus MPA was noted, but there was substantial overlap between basal and postprogestogen therapy serum PP14 concentrations. Serum concentrations of PP14, but not IGFBP-1, were slightly higher in women whose endometrial biopsies demonstrated a P effect, but again, there was substantial overlap with the values found in women whose biopsies showed only an estrogen effect. Serum measurements of IGFBP-1 and PP14 are not useful for monitoring postmenopausal replacement therapy with percutaneous E2 and oral MPA.

Adult↗
PubMed1990

[The cellular localization of the fertility alpha 2-microglobulin in tumors of the reproductive system].

Seventy-five samples of human tumors were examined immunohistochemically for fertility alpha-2-microglobulin also known as progesterone-associated protein of the endometrium. The protein was detected in 35.7% (5 of 14) endometrial cancer samples and in 20% (2 of 10) of ovarian malignancies. Tumors of the stomach, colon, breast, lung and some other sites failed to reveal the antigen with the exception of a single case of pulmonary adenocarcinoma which showed the ectopic expression of the protein. Fertility alpha-2-microglobulin is stage-specific tissue marker of the endometrium. It is expressed at the final stage of cell differentiation and is partially lost in cancer.

Endometrium↗
PubMed1990

The effect of human placental protein 14 (PP14) on the production of interleukin-1 from mitogenically stimulated mononuclear cell cultures.

Crude human decidual tissue extracts containing placental protein 14 (PP14) were shown to inhibit the production of interleukin-1 beta (IL-1) from mitogenically stimulated mononuclear cell cultures. The inhibition was dose-dependent over the range of PP14 concentrations investigated (0-8.0 mg/l) and was effective on both phytohaemagglutinin-(PHA) and lipopolysaccharide- (LPS)-induced IL-1 secretion. Using these culture systems, a PP14 concentration of 1.0 mg/l induced a 34% suppression of IL-1 secretion following LPS stimulation and 22% following PHA stimulation. For PHA stimulation the suppression of IL-1 secretion was effective throughout the culture period investigated (0-89 hr). Individual crude decidual extracts inhibited the incorporation of [3H]thymidine into PHA-stimulated lymphocytes, such inhibition being partially reversed by the addition of exogenous recombinant IL-1 to the cultures. These results suggest that the previously reported immunosuppressive activity of PP14 may be mediated by the suppression of IL-1 secretion.

Cells, Cultured↗
PubMed1986

Measurement of the pregnancy-associated proteins, placental protein 14 and pregnancy-associated plasma protein A in human seminal plasma.

The pregnancy-associated and placental proteins PP14 and PAPP-A have been measured in human seminal plasma from normal men. PP14 was a significant protein constituent in most seminal plasma samples; sometimes comprising over 2.5% of the total protein content. The concentration of PP14 in seminal plasma from men with oligospermia was in the reference range of this protein derived from values measured in normal men. However, about 14% of samples from vasectomized subjects contained concentrations of PP14 less than normal. It was found that the concentration of PAPP-A in seminal plasma from vasectomized men and men with oligospermia also fell within the reference range for this protein. However, the concentration of PAPP-A in seminal plasma was significantly higher in those subjects whose sperm motility was above 60% than in those with a lower percentage motility, suggesting a possible role of this protein in sperm function.

Glycodelin↗