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Biomedical subjects

M Julkunen

Publications and source records attributed to M Julkunen.

At least 37 records · Page 2Linked to original sources
PubMed1988

Primary structure of human insulin-like growth factor-binding protein/placental protein 12 and tissue-specific expression of its mRNA.

The low-molecular-mass insulin-like growth factor-binding protein (IGF-BP) and placental protein 12 (PP12) are identical proteins that are present in human serum, amniotic fluid, secretory endometrium and decidua. IGF-BP/PP12 is believed to act as an autocrine or paracrine regulator of cell growth. A cDNA clone encompassing the entire protein coding region of this protein was isolated from a human decidual cDNA library. The authenticity of the cDNA was verified by in vitro transcription/translation experiments and by the identity of the 10 N-terminal amino acids deduced for the mature peptide with those obtained by direct protein sequencing. The amino acid sequence indicates that pre-IGF-BP/PP12 consists of 259 amino acid residues. The putative signal peptide is 25 residues long, and the mature protein thus contains 234 amino acids and has a molecular mass of 25293 Da. The sequence is very cysteine-rich at the N-terminus after which there are regions of clustered Pro, Glu, Ser and Thr residues (so-called PEST regions), which exist in proteins with short half-lives. The amino acid sequence also includes an Arg-Gly-Asp tripeptide that may function as a cell recognition signal. The IGF-BP/PP12 gene encodes a single 1.6 kb mRNA species that is expressed in decidua, secretory endometrium, liver and a human hepatoma cell line (HepG2). Southern blot analysis suggests that there is a single IGF-BP/PP12 gene in the human genome.

Amino Acid Sequence↗
PubMed1988

Human endometrial proteins.

Human endometrium synthesizes a number of proteins. Two of the major proteins are the low molecular weight insulin-like growth factor-binding protein (IGF-bp25) and endometrial protein PP14 (placental protein 14). Both proteins have been cloned from human decidual cDNA library and their complete amino acid sequences have been deduced. IGF-bp25 is found in various tissues and body fluids including secretory and decidualized endometrium, amniotic fluid, liver, follicular fluid and luteinized granulosa cells of preovulatory ovarian follicles. Clinical studies have shown that there is no systematic variation in the circulating levels during normal menstrual cycle, whereas in hyperstimulated cycles the levels are higher when there are many preovulatory follicles and immediately after follicle aspiration for in vitro fertilization (IVF). Some women with polycystic ovarian disease have a subnormal level of IGF-bp25 in serum. The other protein, PP14, is synthesized by secretory and decidualized endometrium, and it is also abundant in amniotic fluid. PP14 is mainly released by secretory endometrial glands during the last week of ovulatory cycles. There is a consistent variation in serum PP14 levels during normal menstrual cycle. The levels are lowest at the time of ovulation and rise steeply during the last week of luteal phase and peak at the onset of menstruation. Administration of micronized oral progesterone to normally ovulating infertile women brings about elevation in their serum PP14 levels during late luteal phase. In postmenopausal women cyclical estrogen-progestogen replacement causes elevation of serum PP14 level, but this does not take place in hysterectomized postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrium↗
PubMed1988

Complete amino acid sequence of human placental protein 14: a progesterone-regulated uterine protein homologous to beta-lactoglobulins.

Placental protein 14 (PP14), also known as progestagen-dependent endometrial protein and pregnancy-associated endometrial alpha 2-globulin, is synthesized by the human secretory endometrium and decidua. We have isolated from a human decidual cDNA library clones corresponding to PP14 and deduced its entire amino acid sequence. PP14 contains 180 amino acids, 18 of which correspond to a putative signal peptide. The predicted molecular weight of the pre-PP14 is 20,555 and that of the mature protein is 18,787. PP14 is encoded by a 1-kilobase-pair mRNA that is expressed in human secretory endometrium and decidua but not in postmenopausal endometrium, placenta, liver, kidney, and adrenals. The 162-residue-long sequence of PP14 is highly homologous to beta-lactoglobulins, with a 53.4% identity with the amino acid sequence of horse beta-lactoglobulin I. The four cysteinyl residues (positions 66, 106, 119, and 160) responsible for intramolecular disulfide bridges in beta-lactoglobulins are all conserved in PP14. Southern blot analysis of human DNA suggested that PP14 gene sequences encompass some 20 kilobase pairs of the human genomic DNA.

Amino Acid Sequence↗
PubMed1988

Structural studies, localization in tissue and clinical aspects of human endometrial proteins.

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)

Amino Acid Sequence↗
PubMed1987

Progesterone-associated proteins PP12 and PP14 in the human endometrium.

Two proteins, designated as PP12 and PP14 were originally isolated from soluble extracts of the human placenta and its adjacent membranes. We have shown that they are synthesized by decidualized/secretory endometrium and not by placenta. Both proteins occur at high concentrations in human amniotic fluid, which is therefore an excellent source for purification. PP12 is a 34-kDa glycoprotein, which has an N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala. This is identical with that of somatomedin-binding protein purified from the amniotic fluid. PP12 too binds somatomedin-C, or IGF-I (insulin-like growth factor-I). Human secretory endometrium synthesizes and secretes PP12, and progesterone stimulates its secretion. PP14 is a 28-kDa glycoprotein. Its N-terminal sequence shows homology to that of beta-lactoglobulins from various species. We have found PP14 in the human endometrium, serum and milk. Immunologically, PP14 is related to progestagen-associated endometrial protein (PEP), alpha-2 pregnancy-associated endometrial protein (alpha-2, PEG), endometrial protein 15 (EP15), alpha-uterine protein (AUP) and chorionic alpha-2 microglobulin (CAG-2). In ovulatory menstrual cycles, the concentration of PP14 increases in endometrial tissue as the secretory changes advance. In serum, the PP14 concentration begins to rise later than the progesterone levels, and high serum PP14 levels are maintained for the first days of the next cycle. By contrast, no elevation of serum PP14 level is seen in anovulatory cycles. Our results show that progesterone-associated proteins are synthesized by the human endometrium and appear in the peripheral circulation, where they can be quantitatively measured using immunochemical techniques.

Amniotic Fluid↗
PubMed1987

The effect of Danazol on the circulating levels of 34K insulin-like growth factor-binding protein (PP12) and endometrial secretory protein PP14.

Twenty-four women, 11 with endometriosis and 13 with fibrocystic mastopathy, were treated with a medium dose (300-400 mg daily) of Danazol for 6 months. The circulating level of progesterone, the 34K insulin-like growth factor-binding protein (IGF-bp) and endometrial protein PP14 (placental protein 14) were measured by specific radioimmunoassays before and during treatment. The serum progesterone concentration decreased significantly during Danazol treatment, as did the serum levels of 34K IGF-bp and PP14. By the third month of therapy amenorrhoea was observed in 22 out of 24 women and this was accompanied by a further decline in the IGF-bp and PP14 levels. In light of the previous observations on the IGF-bp and PP14 synthesis by secretory endometrium and the fact that Danazol causes endometrial atrophy, these results suggest that Danazol treatment has an effect on endometrial protein secretion.

Adult↗
PubMed1987

Amino acid sequence homology between human placental protein 14 and beta-lactoglobulins from various species.

The primary structure of 22 N-terminal amino acid residues of placental protein 14 was determined by automated Edman degradation with a gas-phase sequencer. This protein, isolated from the human placenta and its membranes, was considered pure as evidenced by a single N-terminal amino acid sequence M D I P Q T K Q D L E L P K L A G T W H S M. It shows significant sequence homology with horse, bovine, buffalo, sheep and goat beta-lactoglobulins. We found 13 identities out of 22 possible matches with horse beta-lactoglobulin. beta-lactoglobulins from several animal species have been found to bind retinol. Among the identical residues there is one tryptophan at position 19 which is conserved in beta-lactoglobulins and is also found in the human retinol-binding protein at the corresponding position. These data suggest a common origin of PP14 and beta-lactoglobulins.

Amino Acid Sequence↗
PubMed1986

Human fallopian tube contains placental protein 14.

Radioimmunoassay and immunoperoxidase staining were used to study the tissue content and localization of an endometrial protein, placental protein 14, in the human fallopian tube. Placental protein 14 immunoreactivity was found in saline extracts from all fallopian tubes tested (n = 14). In the fimbrial part the placental protein 14 content was higher in the secretory than in the proliferative phase (p less than 0.01). No difference was found in the placental protein 14 content between the isthmic, ampullar, and fimbrial parts of the tube. Immunoperoxidase staining localized placental protein 14 to the ciliated and secretory epithelial cells of the mucosa in all parts of the tube regardless of the phase of menstrual cycle. The occurrence of the same protein in the endometrium and fallopian tube is compatible with the common embryonic origin from the müllerian duct of these tissues.

Chromatography, Gel↗
PubMed1986

Human endometrium and menstrual fluid contain placental protein 5 (PP5).

Placental protein 5 (PP5), a serine protease inhibitor, was found in the endometrium and menstrual fluid of non-pregnant women. PP5 was present in all 16 endometrial samples taken at various phases of the menstrual cycle. In the secretory phase, the endometrial PP5 content was higher (median 17.4 micrograms/g protein; n = 8) than in the proliferative phase (median 3.8 micrograms/g protein; n = 8). In gel filtration, endometrial tissue homogenates yielded one immunoreactive peak corresponding to a mol. wt of 28,000 daltons, whereas placental PP5 eluted at 32,000 daltons. In sodium dodecyl sulphate polyacrylamide gel electrophoresis, endometrial PP5 comigrated with purified placental PP5 corresponding to a mol. wt of 30,000 daltons. All menstrual fluid samples (n = 14) contained immunoreactive PP5 at concentrations from 77 to 1150 micrograms/l. The mol. wt of menstrual fluid PP5-immunoreactivity was 13,000 daltons. The dose-response curves of purified PP5 standard and endometrial and menstrual fluid PP5 were parallel in the PP5 radioimmunoassay. The higher concentration of PP5 in secretory endometrium indicates association of PP5 with endocrine events of the menstrual cycle.

Adult↗
PubMed1986

The content and immunohistochemical localization of placental protein 10 (PP10) in the fallopian tube.

Radioimmunoassay, gel filtration and immunoperoxidase staining were used to study the content and localization of placental protein 10 (PP10) in 15 fallopian tubes removed on medical grounds from patients aged between 35 and 53 years. PP10 was consistently present in all parts of the tube at all ages and in all phases of the menstrual cycle. The PP10 concentration in tissue ranged from 0.08 to 2.95 micrograms/g of tubal cytosol protein. Immunoperoxidase staining localized PP10 in monocytic and lymphoid cells that were unevenly scattered in the subepithelial layer of the mucosa. In gel filtration, PP10 from the fallopian tube and purified placental PP10 eluted in the same volume, and graded amounts of PP10-immunoreactive material from the tube and purified PP10 gave parallel dose-response curves in radioimmunoassay. We conclude that PP10 is another 'placental protein' that has been identified in the fallopian tube.

Adult↗
PubMed1986

Synthesis of placental protein 12 by human endometrium.

We have previously shown that placental protein 12 (PP12) is synthesized and secreted by human term pregnancy decidua in vitro. In the present study, fragments of proliferative and secretory phase endometrium were cultured in media in the presence and absence of progesterone (P) and 17 beta-estradiol (E2) for 96 h. The PP12 concentrations in the media and tissues were measured by RIA, and de novo synthesis was investigated by measuring the incorporation of [35S]methionine into PP12. Before culture, PP12 could not be detected in any proliferative endometria, whereas all secretory endometria contained PP12. All secretory endometria released PP12 into the medium in the presence and absence of added P and E2. Secretory endometria released significantly more PP12 than proliferative endometria. Three of seven proliferative endometria did not release PP12 in the absence of P, but all did so after P had been added. The addition of P to culture medium caused a 2.4-to over 71-fold increase in PP12 secretion over control values in proliferative endometria and up to a 3.5-fold increase in secretory endometrium. E2 had no significant effect. Cycloheximide totally inhibited the PP12 release induced by P from proliferative endometrium, and in secretory endometrium, it either totally blocked PP12 release or inhibited the stimulation due to P. [35S]Methionine was incorporated into immunoprecipitable PP12 in cultures of secretory and P-treated proliferative phase endometria. These results demonstrate de novo synthesis of PP12 by nonpregnant endometrium in tissue culture and suggest that the biosynthesis and secretion of PP12 by nonpregnant endometrium are regulated by P.

Culture Techniques↗
PubMed1986

Secretory endometrium synthesizes placental protein 14.

Saline extracts of human nonpregnant endometrium were found to contain placental protein 14 (PP14). The tissue PP14 content was highest in the late secretory phase (median, 7.7 mg/g protein; n = 14), whereas proliferative endometrium (n = 8) was either PP14 negative or showed a low PP14 content (median, 0.15 mg/g protein). By immunoperoxidase staining, PP14 was localized in the glandular epithelial cells of endometrium. In tissue culture, secretory endometrium released more PP14 than proliferative endometrium, and cycloheximide markedly decreased this release. Synthesis of PP14 by secretory endometrium was demonstrated by incorporation of [35S]methionine into immunoprecipitable PP14. These results show that PP14 is synthesized and secreted by the nonpregnant endometrium.

Culture Techniques↗
PubMed1986

Human decidua synthesizes placental protein 14 (PP14) in vitro.

Human decidua was found to synthesize and secrete placental protein 14 (PP14). The presence of PP14 in tissue explants of decidua, foetal membranes and placenta from term pregnancy was demonstrated by radioimmunoassay. The PP14 content in decidua (1300 +/- 410 ng/100 mg tissue) was higher than in chorion (570 +/- 120 ng/100 mg; P less than 0.01), amnion (240 +/- 100 ng/100 mg; P less than 0.001) or placenta (300 +/- 130 ng/100 mg; P less than 0.001). Three to 36 times more PP14 was released into culture medium by decidual explants compared with the other tissues, and cycloheximide decreased this release by 39%. Placental tissues released hardly any PP14. Decidual synthesis of PP14 was demonstrated by incorporation of [35S]methionine into immunoprecipitable PP14 in tissue culture.

Autoradiography↗
PubMed1986

Is decidua affected in gestational hypertension? Indication by elevated PP14 levels.

The serum concentration of placental protein 14 (PP14) was measured by radioimmunoassay in 129 apparently healthy pregnant women at 33-40 weeks, and the results were compared with those of 40 women with gestational hypertension either with or without proteinuria at similar weeks. In normal pregnancy, maternal serum PP14 levels decreased towards term. Therefore, the results were expressed as multiples of the normal median for each week. In gestational hypertension, the values were higher than normal (p less than 0.001): they were above the normal median in 32 (80%) cases (p less than 0.005), and above the normal 90th percentile in 15 (38%) cases (p less than 0.001). The presence or absence of proteinuria did not affect the result. Since recent findings suggest that PP14 is synthesized by late pregnancy decidua and not by the placenta, our results suggest that decidua may be affected in gestational hypertension.

Adolescent↗