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See detailStimulation of human trophoblast invasion by placental growth hormone
Lacroix, M. C.; Guibourdenche, J.; Fournier, T. et al

in Endocrinology (2005), 146(5), 2434-2444

A critical step in establishment of human pregnancy is the invasion of the uterus wall by the extravillous cytotrophoblast (EVCT), a process regulated by multiple autocrine and paracrine factors. Hormones ... [more ▼]

A critical step in establishment of human pregnancy is the invasion of the uterus wall by the extravillous cytotrophoblast (EVCT), a process regulated by multiple autocrine and paracrine factors. Hormones belonging to the GH/prolactin family are expressed at the maternofetal interface. Because they are involved in cell motility in various models, we examined the possible regulatory role of human placental GH (hPGH) in EVCT invasiveness. By using an in vitro invasion model, we found that EVCT isolated from first-trimester chorionic villi and cultured on Matrigel secreted hPGH and expressed human GH receptor ( hGHR). These data were confirmed by in situ immunohistochemistry. EVCT expressed the full-length and truncated forms of hGHR, and the Janus kinase-2/signal transducer and activator of transcription factor-5 signaling pathway was activated in EVCT by hPGH treatment. Strong hPGH and hGHR expression was observed when EVCT invaded Matrigel and moved through the pores of the filter on which they were cultured. hPGH stimulated EVCT invasiveness, and this effect was inhibited by a Janus kinase-2 inhibitor. Interestingly, hPGH was more efficient than pituitary GH in stimulating EVCT invasiveness. These results offer the first evidence for a placental role of hPGH and suggest an autocrine/ paracrine role of hPGH in the regulation of trophoblast invasion. [less ▲]

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See detailPlacental GH, IGF-I, IGF-binding protein-1 and leptin during a glucose challenge test in pregnant women : relation with maternal body weight, glucose tolerance, and birth weight
Verhaeghe, J.; Pintiaux, Axelle ULg; Van Herck, E. et al

in Journal of Clinical Endocrinology and Metabolism (2002), 87(6), 2875-2882

The prediction of birth weight may be improved by the measurement of hormones or growth factors in the mother. We measured body weight (BW) and plasma levels of placental GH (PGH), IGF-I, IGF-binding ... [more ▼]

The prediction of birth weight may be improved by the measurement of hormones or growth factors in the mother. We measured body weight (BW) and plasma levels of placental GH (PGH), IGF-I, IGF-binding protein-1 (IGFBP-1), and leptin at the time of the glucose challenge test (GCT) in 289 women, who were pregnant with a single fetus, between 24 and 29 wk gestational age (GA). Delivery occurred 12 +/- 2 (mean +/- SD) wk later. First, we examined which variables regulate these hormonal factors. Multiple regression showed that PGH concentrations were determined by GA at sampling and were negatively related to BW. IGF-I levels were mainly determined by PGH, and also by insulin, BW, and (negatively) age. IGFBP-1 concentrations were negatively determined by BW, insulin, and IGF-I. BW was also a powerful determinant of leptin levels, with insulin as a less robust determinant. Second, we examined the relation to glucose levels. PGH, IGF-I, and IGFBP-1 concentrations were not correlated with post-GCT glucose levels and were comparable in women with a normal or disturbed GCT (glucose >/=7.8 mmol/liter; n = 72). Finally, we examined the relation with birth weight and placental weight. Birth weight, corrected for GA and stratified into percentile groups, and the ponderal index at birth were strongly related to maternal BW, but not to maternal PGH, IGF-I, or IGFBP-1 levels. Neither was maternal leptin related to birth weight, but leptin concentrations were slightly higher in women who delivered obese babies. Placental weight was not related to any of the hormonal factors. This prospective study indicates that the variation in circulating PGH, IGF-I, IGFBP-1, and leptin between 24 and 29 wk of pregnancy is strongly dependent on maternal BW, but is unrelated to glucose tolerance. In addition, the measurement of PGH, IGF-I, IGFBP-1, or leptin at the time of the GCT is not useful clinically to predict birth weight. [less ▲]

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See detailPlacental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: Correlations with fetal growth
McIntyre, H. D.; Serek, R.; Crane, D. I. et al

in Journal of Clinical Endocrinology and Metabolism (2000), 85(3), 1143-1150

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a ... [more ▼]

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFSP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-5 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGK at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P <.001), free PGH and total PGH correlated very closely (r = 0.98). The results are consistent with an inhibitory function for GHBP in vivo and support a critical role for placental GH and IGF-I in driving normal fetal growth. [less ▲]

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See detailTolerance to the Foeto-Placental 'Graft': Ten Ways to Support a Child for Nine Months
Thellin, Olivier ULg; Coumans, Bernard ULg; Zorzi, Willy ULg et al

in Current Opinion in Immunology (2000), 12(6), 731-7

Tolerance to the foetal 'allograft' has been extensively studied in the past few years, providing interesting new insights. In addition to a potential role for HLA-G, which has been widely discussed ... [more ▼]

Tolerance to the foetal 'allograft' has been extensively studied in the past few years, providing interesting new insights. In addition to a potential role for HLA-G, which has been widely discussed, there are hypotheses suggesting roles for several other molecules or cells: leukemia inhibitory factor and its receptor; indoleamine 2. 3-dioxygenase; the Th1/Th2 balance; suppressor macrophages; hormones such as progesterone or the placental growth hormone; CD95 and its ligand; and, as recently proposed, annexin II. Tolerance of the foetal allograft is probably the consequence of a wide panel of mechanisms that may or may not be pregnancy-specific, that are of major or secondary importance and that may be interconnected. [less ▲]

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See detailLimited effects of placental and pituitary growth hormone on cytokine expression in vitro
Thellin, Olivier ULg; Coumans, Bernard ULg; Devos, Sébastien ULg et al

in European Cytokine Network (2000), 11(3), 452-455

The hypothesis that growth hormone (GH) can affect immune responses in man has been evaluated by monitoring cytokine expression in cultures from peripheral blood mononuclear cells, by enzyme-linked ... [more ▼]

The hypothesis that growth hormone (GH) can affect immune responses in man has been evaluated by monitoring cytokine expression in cultures from peripheral blood mononuclear cells, by enzyme-linked immunosorbent assay (ELISA) and ribonuclease protection assay, and in tonsillar cells by ELISA. In addition to pituitary GH (GH-N), the placental form (GH-V), differing from pituitary GH by 13 amino acids has also been tested. Only few effects reached statistical significance and were in no case greater than 15%. Pituitary GH slightly reduced IL-5 production and stimulated IFN-gamma production. The latter effect was also observed with prolactin and could thus be induced through the prolactin receptor. It is proposed that GH has no strong effects on the parameters investigated, possibly as a result of redundancy in the cytokine network. Alternatively, effects on leukocytes are mediated by other tissues such as the liver or are clear only in response to stronger challenges. [less ▲]

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See detailPlacental growth hormone and IGF-I in a pregnant woman with Pit-1 deficiency
Verhaeghe, J.; Bougoussa, M.; Van Herck, E. et al

in Clinical Endocrinology (2000), 53(5), 645-647

The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women have not been well established. We measured the serum concentrations of placental growth hormone (PGH) and ... [more ▼]

The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women have not been well established. We measured the serum concentrations of placental growth hormone (PGH) and IGF-I in a woman with pit-1 deficiency before, during and after pregnancy, resulting in the birth of a healthy child (not pit-1 deficient). Both PGH and IGF-I concentrations were below the assay detection limit before and after pregnancy. During pregnancy, PGH and IGF-I levels increased steadily; the concentrations of PGH and IGF-I in late pregnancy were comparable with levels previously measured in normal pregnancies. PGH and IGF-I concentrations were strongly correlated throughout pregnancy (r = 0.90; P = 0.002). PGH was undetectable in cord serum, whilst the IGF-I concentration was within the normal range. The findings of this case study corroborate the notion that PGH is the prime regulator of maternal serum IGF-I during pregnancy. [less ▲]

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See detailLymphoid cell apoptosis induced by trophoblastic cells: a model of active foeto-placental tolerance
Coumans, Bernard ULg; Thellin, Olivier ULg; Zorzi, Willy ULg et al

in Journal of Immunological Methods (1999), 224(1-2), 185-196

To test the hypothesis that CD95-L (Fas-L) present on trophoblastic cells plays a part in establishing foeto-placental tolerance by inducing apoptosis of immune defence cells, we cocultured trophoblasts ... [more ▼]

To test the hypothesis that CD95-L (Fas-L) present on trophoblastic cells plays a part in establishing foeto-placental tolerance by inducing apoptosis of immune defence cells, we cocultured trophoblasts with lymphoid cells and scored the frequency of cell death in these cultures. We prepared human trophoblastic cells from term placentas removed by C-section and placed them in culture for 48 h before introducing the lymphoid cells. We added Jurkat cells, a CD3 + lymphoid cell line, or purified T cells from human blood to the cultured trophoblasts and monitored apoptosis by electron microscopy and flow cytometry after TUNEL or annexin V labelling. The frequency of cell death in the CD3 + cell population was higher when the lymphoid cells were cocultured with trophoblastic cells than when they were cultured alone. This frequency increased with time but was reduced when anti-CD95-L antibodies were added to the culture medium. Cell death was less frequent in the lymphoid cell population when trophoblasts were replaced with human fibroblasts not expressing CD95-L. (C) 1999 Elsevier Science B.V. All rights reserved. [less ▲]

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See detailHousekeeping Genes as Internal Standards: Use and Limits
Thellin, Olivier ULg; Zorzi, Willy ULg; Lakaye, Bernard ULg et al

in Journal of Biotechnology (1999), 75(2-3), 291-5

Quantitative studies are commonly realised in the biomedical research to compare RNA expression in different experimental or clinical conditions. These quantifications are performed through their ... [more ▼]

Quantitative studies are commonly realised in the biomedical research to compare RNA expression in different experimental or clinical conditions. These quantifications are performed through their comparison to the expression of the housekeeping gene transcripts like glyceraldehyde-3-phosphate dehydrogenase (G3PDH), albumin, actins, tubulins, cyclophilin, hypoxantine phsophoribosyltransferase (HRPT), L32. 28S, and 18S rRNAs are also used as internal standards. In this paper, it is recalled that the commonly used internal standards can quantitatively vary in response to various factors. Possible variations are illustrated using three experimental examples. Preferred types of internal standards are then proposed for each of these samples and thereafter the general procedure concerning the choice of an internal standard and the way to manage its uses are discussed. [less ▲]

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See detailExpression of Growth Hormone Receptors by Lymphocyte Subpopulations in the Human Tonsil
Thellin, Olivier ULg; Coumans, Bernard ULg; Zorzi, Willy ULg et al

in Developmental Immunology (1998), 6(3-4), 295-304

The ability of human tonsillar lymphoid cells to express growth hormone receptor (hGH-N-R) was analyzed by flow cytometry. FITC-coupled recombinant human growth hormone (hGH-N) was used to reveal the ... [more ▼]

The ability of human tonsillar lymphoid cells to express growth hormone receptor (hGH-N-R) was analyzed by flow cytometry. FITC-coupled recombinant human growth hormone (hGH-N) was used to reveal the receptors, in combination with phenotype markers. Unlike T cells, tonsillar B cells constitutively express the hGH-N receptor. Quiescent cells separated from activated cells by Percoll-gradient centrifugation bear fewer receptors than activated ones. Activated T cells express hGH-N-R, but the typical germinal centre CD4+ CD57+ T cells do not. These latter thus appear not to be fully activated. Inside the lymph follicles, the germinal centre CD38+ B-cell population and the mantle-zone CD39+ B-cell population display similar levels of hGH-N-R expression, but receptor density is lower on dividing dark-zone CD38+ CD10+ B cells. Different lymphoid-cell populations thus differ markedly in their ability to express the growth hormone receptor, in relation notably to their activation status. This highlights the link between the neuroendocrine system and the active immune defense. [less ▲]

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See detailDemonstration of the expression of CD95 ligand transcript and protein in human placenta
Zorzi, Willy ULg; Thellin, Olivier ULg; Coumans, Bernard ULg et al

in Placenta (1998), 19(4), 269-277

Tolerance of the fetal allograft enables the human conceptus to implant itself into the maternal uterus and survive and grow there. This tolerance phenomenon remains largely obscure, notably because it ... [more ▼]

Tolerance of the fetal allograft enables the human conceptus to implant itself into the maternal uterus and survive and grow there. This tolerance phenomenon remains largely obscure, notably because it appears to be controlled by multiple mechanisms. CD95 ligand (CD95-L), which can trigger death of CD95-positive cells by apoptosis, may participate in inducing anti-fetus-sensitized CD95-positive T lymphocytes to enter apoptosis. Using immunohistochemistry (first trimester and term placentae), FAGS assays (term placenta) and RT-PCR assays (term placenta), the presence of CD95-L protein and mRNA has been shown in crude placental tissue preparations and isolated placental cells. Among the latter, CD95-L expression was detected in trophoblastic cells, fetal blood cells (mRNA only) and also the Hofbauer macrophages. No CD95-L was detected in fibroblasts or fetal endothelial cells. Thus trophoblastic cells, Hofbauer macrophages, and perhaps also fetal blood cells could form a sequential barrier blocking maternal activated defence cells bearing CD95 molecules. (C) 1998 W. B. Saunders Company Ltd. [less ▲]

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See detailBoth Pituitary and Placental Growth Hormone Transcripts Are Expressed in Human Peripheral Blood Mononuclear Cells (Pbmc)
Melen-Lamalle, Laurence ULg; Hennen, Georges ULg; Dullaart, R. P. et al

in Clinical & Experimental Immunology (1997), 110(2), 336-40

The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered ... [more ▼]

The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered to be exclusively expressed in human placenta, where it replaces maternal circulating hGH-N at the end of pregnancy. In this study we investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis hGH-N, and hGH-V, gene expression in PBMC in men, women and pregnant women. We have demonstrated that hGH-N and hGH-V transcripts are simultaneously produced by PBMC in both men and women as well as pregnant women. The PBMC of a PIT-1-negative woman expressed only the hGH-V transcript, but not the hGH-N one as expected. In conclusion, hGH-V mRNA is expressed by cells other than the syncytiotrophoblast, is not regulated by PIT-1, and may be involved in immune regulation, as is pituitary GH. [less ▲]

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See detailExpression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy.
Caron, Philippe; Buscail, Louis; Beckers, Albert ULg et al

in Journal of Clinical Endocrinology and Metabolism (1997), 82(11), 3771-3776

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma ... [more ▼]

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery. In placental membranes from both treated and healthy untreated patients, we demonstrated the presence of high affinity binding sites for somatostatin-14 (Kd, 4.6 and 5.3 nmol/L; binding capacity, 1.53 and 1.35 pmol/mg protein, respectively). These receptors displayed low affinity for octreotide (IC50, 1.2-2 mumol/L), suggesting the presence of SST1 and/or SST4 receptors. We found that messenger ribonucleic acids of these two subtypes were expressed in both human placental tissue and purified human cytotrophoblast cells. Finally, the SST1-selective analog, des-AA1,2,5[D-Trp8,IAmp9]S-14 had low affinity for placental somatostatin receptors. These results argue in favor of the presence of the SST4 subtype in human placenta. At the doses administered, octreotide did not bind to placental somatostatin receptors. Our results may explain the absence of changes in both human placental GH and IGF-I concentrations that we observed during octreotide treatment. [less ▲]

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See detailGlucose inhibits human placental GH secretion, in vitro
Patel, N.; Alsat, E.; Igout, Ahmed ULg et al

in Journal of Clinical Endocrinology and Metabolism (1995), 80(5), 1743-6

Human placenta specifically expresses the GH-V gene leading to the production of placental Growth Hormone (PGH). During pregnancy, PGH levels increase progressively in maternal blood, but its regulation ... [more ▼]

Human placenta specifically expresses the GH-V gene leading to the production of placental Growth Hormone (PGH). During pregnancy, PGH levels increase progressively in maternal blood, but its regulation remains unknown. In this study the effect of glucose on PGH secretion by human term placenta was tested, in vitro, by means of two different experimental models: organ culture of villous tissue and primary culture of isolated cytotrophoblasts. PGH was assayed in the culture medium by an immunoradiometric assay using a specific PGH monoclonal antibody. The presence of glucose (25 mmol/L) in the culture medium significantly inhibited (p < 0.001) the secretion of PGH by either placental villous explants or by cultured trophoblast cells. This inhibitory effect of glucose on PGH secretion was dose-dependent. More than 50% inhibition being observed with 5.5 mmol/L. In the same conditions, the daily production of hPL and hCG, were unmodified. Furthermore, the glucose-induced inhibition of PGH secretion was more effective when cultured trophoblast cells are differentiated into syncytiotrophoblast. This study demonstrates, for the first time, that among the gestational polypeptide hormones secreted by the human placenta, only PGH secretion is modulated by glucose, suggesting a key metabolic role for this hormone during pregnancy. [less ▲]

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See detailPurification and Biochemical Characterization of Recombinant Human Placental Growth Hormone Produced in Escherichia Coli
Igout, Ahmed ULg; Van Beeumen, Jozef; Frankenne, Francis ULg et al

in Biochemical Journal (1993), 295(3), 719-724

The hGH-V (or hGH-2) gene codes for human placental growth hormone (hPGH). Secretion of hPGH is continuous, in contrast with the pulsed secretion of pituitary growth hormone (hGH) which it progressively ... [more ▼]

The hGH-V (or hGH-2) gene codes for human placental growth hormone (hPGH). Secretion of hPGH is continuous, in contrast with the pulsed secretion of pituitary growth hormone (hGH) which it progressively replaces in the maternal bloodstream. hGH- V cDNA has previously been cloned and isolated. Analysis of its nucleotide sequence has revealed a 191-residue protein, hPGH, differing from hGH at 13 positions. The calculated pI is more basic than that of the pituitary hormone. Here we have inserted hGH- VcDNA into the pIN-III-ompA3 plasmid in order to produce hPGH in its native form in Escherichia coli D1210. Expression of hGH- V cDNA in E. coli is significantly lower than that of hGH cDNA with the same expression system. The hPGH produced in E. coli was purified in quantities sufficient to allow its biochemical and immunochemical characterization. The molecular mass of the protein was determined by electrospray m.s. The determined mass, 22320 Da, agrees well with the molecular mass calculated from the translated cDNA sequence, assuming the presence of two disulphide bridges. Having established the technique for producing hPGH with a primary structure identical to the natural, non-glycosylated, 22 kDa isoform, we can now plan the full physicochemical and pharmaceutical characterization of this new hormonal entity. [less ▲]

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See detailSYNCYTIOTROPHOBLASTIC LOCALIZATION OF THE HUMAN GROWTH-HORMONE VARIANT MESSENGER-RNA IN THE PLACENTA
Scippo, Marie-Louise ULg; Frankenne, Francis ULg; HOOGHEPETERS, ELisabeth et al

in Molecular & Cellular Endocrinology (1993), 92(2), 7-13

The hGH/hCS genes, clustered on chromosome 17 in the 5' to 3' order GH-N, CS-L, CS-A, GH-V and CS-B, show a high degree of sequence identity. The expression product of the GH-V gene is the placental ... [more ▼]

The hGH/hCS genes, clustered on chromosome 17 in the 5' to 3' order GH-N, CS-L, CS-A, GH-V and CS-B, show a high degree of sequence identity. The expression product of the GH-V gene is the placental growth hormone, which replaces pituitary GH in maternal blood throughout pregnancy. By means of mRNA competitive hybridization using P-32-labelled and unlabelled 30 bases long oligonucleotides, we first optimized specific hybridization conditions. In situ hybridization was then performed to locate the GH-V mRNA encoding placental growth hormone. The hGH-V gene appears expressed in the placental syncytiotrophoblast. Unlike the CS-A and CS-B genes (both encoding hPL) which are expressed uniformly in the syncytiotrophoblast, the GH-V mRNA is located in a few syncytiotrophoblast cells only. [less ▲]

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See detailEvidence for the expression of growth hormone receptors in human placenta
Frankenne, Francis; Alsat, Eliane; Scippo, Marie-Louise ULg et al

in Biochemical and Biophysical Research Communications (1992), 182(2), 481-486

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See detailHormone de croissance placentaire humaine : expression par génie génétique et relation structure-activité
Igout, Ahmed ULg; Frankenne, Francis; Scippo, Marie-Louise ULg et al

in Revue Française d'Endocrinologie Clinique, Nutrition, et Métabolisme (La) (1992), 3

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See detailHuman placental growth hormone
Frankenne, Francis; Evain-Brion, Danielle; Alsat, Eliane et al

in Anales Espanoles de Pediatria (1992), 36(50), 77-80

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