Placental Growth Hormone Levels Research Articles

Racial differences in the associations between adiposity, placental growth hormone and inflammatory cytokines in pregnant women.

The prevalence of obesity among women of child-bearing age has contributed to an increased risk of pregnancy complications with a disproportional impact on women of lower socioeconomic status and among certain racial groups. In particular, socio-demographic and historical factors have resulted in higher rates of premature births and small-for-gestational age infants among Black women, which may be associated with placental function during pregnancy. The current study investigated the influence of maternal pre-pregnancy adiposity and race on the associations between inflammatory proteins, placental growth hormone (PGH), and infant birthweight. This information was collected for a subsample of 109 participants (Black, n = 39 vs. White, n = 70) from the Brain and Early Experiences (BEE) study. Serum samples were acquired late in the second trimester to assess PGH levels, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin-1 receptor antagonist (IL-1Ra). Participant questionnaire responses provided information on pre-pregnancy BMI, health, race, educational attainment, and infant birthweight. Bivariate correlations and multiple linear regression models were utilized to evaluate associations by race between preconception adiposity, inflammatory markers and PGH. After controlling for covariates including maternal age and education, gestational age, and fetal sex, regression models indicated that pre-pregnancy BMI was negatively associated with PGH (β=-0.42, p<0.05) and IL-8 was positively associated with PGH (β=0.35, p<0.05) among the Black mothers only; neither were significantly associated with PGH in the White mothers. When extending models to birth outcomes, BMI was positively associated with birthweight corrected for gestational age (BWz) (β=0.24, p<0.05) and educational attainment was negatively associated with BWz (β=0.28, p<0.05) for infants of White women. In contrast, neither variable was predictive of BWz for infants of Black mothers. Future work is needed to investigate racial differences in the association between adiposity and placental functioning, which are likely to contribute to differential effects on pregnancy outcomes and fetal growth.

Lower levels of placental growth hormone in early pregnancy in women with type 1 diabetes and large for gestational age infants

ObjectiveTo evaluate whether levels of placental growth hormone (GH) and Insulin-like Growth Factor-I (IGF-I) are associated with development of LGA infants in pregnant women with type 1 diabetes. DesignObservational study of 103 consecutive pregnant women with long-term type 1 diabetes and median HbA1c 6.6% (range 4.9–10.5) (49mmol/mol (30–91)) in early pregnancy. At 8, 14, 21, 27 and 33weeks weight was recorded and blood was sampled for measurements of placental GH, IGF-I and HbA1c. LGA was defined as birth weight >90th percentile after adjustment for gender and gestational age. ResultsThroughout pregnancy placental GH levels were similar in 51 (50%) women delivering LGA infants compared with the remaining women except at 8weeks where placental GH levels were lower in women with LGA infants (1.1ng/ml (0.1–4.3) vs. 1.7 (0.3–11.7), p=0.04). IGF-I levels were similar in women with and without LGA infants (p=0.97). Gestational age at first blood sampling was similar in women with and without LGA infants (60days (37–89) vs. 61.5 (42–94), p=0.42). Placental GH levels at 14weeks correlated negatively with weight gain in early pregnancy (r=−0.32, p=0.002). As predictors of LGA infants, multivariate logistic regression analysis identified placental GH levels at 8weeks (OR 0.4 (95% CI: 0.2–0.9), p=0.02), HbA1c at 33weeks (3.6 (1.3–9.9), p=0.01) and parity ≥1 (3.1 (1.3–7.5), p=0.01) after adjustment for pre-pregnancy BMI. ConclusionsWomen delivering LGA infants had lower placental GH levels in early pregnancy. Growth factors and maternal weight gain in early pregnancy may be important for healthy fetal growth.

Placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I) and ghrelin in pregnant women’s blood serum

The aim of this work is to evaluate levels of placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I) and ghrelin in pregnant women's blood serum before, during and after delivery. Furthermore, the aim is to search for links and interdependence of GH1, PGH and IGF-I concentrations. Seventy nine blood samples were taken one to two hours before, during and half an hour after expulsion of placenta. All proteins studied were determined by ELISA method, using ELISA Kit. The highest PGH concentration and IGF-I concentration in pregnant women's blood serum was observed before delivery while GH1 concentration was lowest. During and after delivery PGH and IGF-I concentration decreased proportionately and pituitary growth hormone concentration increased accordingly. About half an hour after delivery of the placenta, GH1 concentration was highest. In pregnant women's blood there is a metabolic interdependence between PGH and IGF-I. Their concentration increases proportionately during pregnancy and decreases after delivery. It appears that labor and delivery releases GH1 blockade, which level rises three-fold during delivery. After parturition its role and concentration returns to levels before pregnancy.

Pregnancy-induced increase in circulating IGF-I is associated with progression of diabetic retinopathy in women with type 1 diabetes

Objective To evaluate the influence of Insulin-like Growth factor-I (IGF-I) and Placental Growth Hormone (GH) on progression of diabetic retinopathy during pregnancy in women with type 1 diabetes. Design Observational study of 88 consecutive pregnant women with type 1 diabetes for median 16.5 years (range 1–36) and HbA 1c 6.6% (5.2–10.5) in early pregnancy. At 8, 14, 21, 27 and 33 weeks blood samples were drawn for measurement of IGF-I, placental GH and Hemoglobin A 1c (HbA 1c) and blood pressure was recorded. Fundus photography was performed at 8 and 27 weeks. Diabetic retinopathy was classified in five stages. Progression was defined as deterioration of at least one stage of diabetic retinopathy and/or development of macular edema on at least one eye. Results Placental GH and IGF-I levels increased throughout pregnancy and new onset or progression of diabetic retinopathy occurred in 22 (25%). A steeper increase in women with progression of diabetic retinopathy resulted in higher IGF-I levels at 27 weeks ( p = 0.01) and 16% higher IGF-I levels throughout pregnancy ( p = 0.02) compared with women without progression while similar levels of placental GH ( p = 0.58) and HbA 1c ( p = 0.85) were observed throughout pregnancy. In a multivariate logistic regression analysis, progression of diabetic retinopathy was associated with higher IGF-I levels at 33 weeks (odds ratio 2.0 [95% confidence interval 1.1–3.6], p = 0.02) and higher systolic blood pressure at 8 weeks (1.9 [1.1–3.2], p = 0.02) independent of placental GH and HbA 1c levels. Conclusions Pregnancy-induced increase in IGF-I levels is associated with progression of diabetic retinopathy in women with type 1 diabetes.

Maternal serum placental growth hormone, but not human placental lactogen or insulin growth factor‐1, is positively associated with fetal growth in the first half of pregnancy

To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy. Data on 8215 singleton fetuses from the Copenhagen First Trimester Study with measurements of BPD from ultrasound scans performed at weeks 11-14 and 17-21 of pregnancy were analyzed. Growth rate was defined as millimeters of growth/day of BPD between the two scans. Fetuses with growth rate below the 2.5(th) centile (low growth rate, n = 203) and above the 97.5(th) centile (high growth rate, n = 203) were identified. As a reference group 212 fetuses with growth rate around the median were identified (intermediate growth rate). Out of the 618 selected cases in the three growth rate groups a total of 463 cases had a blood sample taken at the time of first-trimester ultrasound (5.6% of the original sample size of 8215 pregnancies). The maternal blood serum concentrations of hPL, PGH and IGF-1 were determined in the three different growth-rate groups. Linear regression analysis without adjustment and with adjustment for known and potential confounders was used to compare serum levels between the groups. Simple linear regression showed a difference in serum level of log(10) PGH between the high and intermediate growth-rate groups (P = 0.037). When adjusted for maternal weight and crown-rump length, multiple linear regression analysis confirmed this difference, as fetuses with high growth rates had a 12% (95% confidence interval, 2-20%; P = 0.009) higher maternal serum level of PGH than those with intermediate growth rates. No differences in hPL and IGF-1 levels between the three different growth-rate groups were found after simple and multiple linear regression analysis. Maternal PGH levels are higher in women carrying fetuses with high first-trimester growth rates than in controls, both in a simple unadjusted analysis and in analyses adjusted for known and potential confounders. Thus, PGH may be involved in fetal growth regulation as early as in the first trimester of pregnancy.

Lower levels of circulating IGF‐I in Type 1 diabetic women with frequent severe hypoglycaemia during pregnancy

Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin-like growth factor I (IGF-I) levels. A prospective, observational study of 107 consecutive pregnant women with Type 1 diabetes. Blood samples were drawn for IGF-I and placental GH analyses at 8, 14, 21, 27 and 33 weeks. Severe hypoglycaemic events were reported within 24 h. Eleven women (10%) experienced frequent severe hypoglycaemia (> or = 5 events), accounting for 60% of all events. Throughout pregnancy, IGF-I levels were 25% lower in these women (P < 0.005) compared with the remaining women, despite similar placental GH levels. Eighty per cent of the severe hypoglycaemic events occurred before 20 weeks when IGF-I levels were at their lowest. This finding was not explained by differences in insulin dose, median plasma glucose levels or glycated haemoglobin. History of severe hypoglycaemia the year preceding pregnancy and impaired hypoglycaemia awareness-being the only predictors of frequent severe hypoglycaemia in a logistic regression analysis-were not associated with IGF-I or placental GH levels at 8 weeks. In women with Type 1 diabetes experiencing frequent severe hypoglycaemia during pregnancy, IGF-I levels are significantly lower compared with the remaining women despite similar placental GH levels. IGF-I levels are lowest in early pregnancy where the incidence of severe hypoglycaemia is highest. IGF-I may be a novel factor of interest in the investigation of severe hypoglycaemia in patients with Type 1 diabetes.

Regulation of Placental Growth Hormone Secretion in a Human Trophoblast Model—The Effects of Hormones and Adipokines

Placental growth hormone (PGH) is secreted from the human placental syncytiotrophoblast into the maternal circulation. PGH levels in pregnant women correlate with the birth weight of their offspring. We hypothesized that metabolic regulators may alter PGH secretion. BeWo cells as human trophoblast models were treated for 24, 48, and 72 h with insulin, insulin-like growth factor (IGF)-1, cortisol, ghrelin, leptin and visfatin. Cyclic-adenosinmonophosphate treatment served as positive control. PGH concentrations in culture media were measured. Insulin reduced (p < 0.008; analysis of variance) PGH secretion from BeWo cells after 72 h. No effect was found when treating cells with IGF-1. Cortisol reduced PGH secretion after 48 h (p < 0.00118; analysis of variance) and 72 h (p < 0.015). Leptin and ghrelin both suppressed (p < 0.027 and p < 0.017, paired t test) whereas visfatin increased (p < 0.014, paired t test) PGH secretion at 72 h. Cyclic adenosinmonophosphate increased (p < 0.003) PGH secretion at 72 h. Our results indicate that in vitro PGH secretion by BeWo cells is regulated by hormonal factors and adipokines. We speculate on the existence of a maternal-placental regulatory loop, in which elevated insulin and leptin levels might down-regulate PGH secretion.

Effects of Glucose, Glycerol, 3-Hydroxybutyrate, Insulin, and Leptin on Placental Growth Hormone Secretion in Placental Explants

Placental growth hormone (PGH) is secreted from the syncytiotrophoblast in increasing amounts during pregnancy. The physiology and regulation of PGH is not well known; however, low glucose levels appear to stimulate PGH liberation IN VITRO and IN VIVO. PGH appears to have lipolytic effects, and inverse correlations between maternal body mass index and serum PGH levels have been reported. Therefore, substances related to maternal adipose tissue metabolism could influence PGH secretion. The effect of insulin, glycerol, 3-hydroxybutyrate (3-OHB), and leptin on PGH and human placental lactogen (hPL) secretion from cultured placental explants was studied. In glucose-free media, PGH content increased upto 237.5+/-28.4% of control media (p<0.001, ANOVA). Insulin levels were without effect on PGH secretion, as were 3-OHB, leptin, and glycerol at 0.02 mmol/l. Glycerol at 0.2 mmol/l increased PGH in all of the placental explants studied (n=8; mean increase 27.3+/-7.1%), and this difference was significantly different from the control explants (p=0.004). The liberation of hPL to culture media was different from PGH and was influenced by glucose and insulin. In conclusion, the absence of glucose profoundly increased PGH secretion in cultured placental explants. Addition of glycerol in physiologically relatively high concentrations showed a less pronounced stimulatory effect.

Peripartum maternal and foetal ghrelin, growth hormones, IGFs and insulin interrelations

Ghrelin may influence GH secretion and is associated with insulin sensitivity. In pregnancy, placental growth hormone (PGH) replaces GH. The aim of this study was to investigate the relationship between PGH and ghrelin and their relationship to insulin sensitivity in pregnancy. Prospective, descriptive study. Thirty-seven singleton pregnant and six twin pregnant women Maternal blood samples were drawn before and 2 days after elective caesarian section (CS). Serum total ghrelin, PGH, GH, GH-binding protein, insulin and IGF-I and IGF-II, and plasma glucose were determined. Insulin sensitivity indices (ISIs) were calculated. Cord blood samples were drawn at delivery for ghrelin determination. Serum ghrelin only displayed a minimal, although statistically significant, decrease after CS. Prior to delivery serum PGH increased by 25% during fasting, and was undetectable the day after CS. Serum levels of GH were low until 48 h after CS. No significant correlations were detected between PGH or ghrelin and ISIs, although a trend was observed for ghrelin. Twin pregnancies had higher PGH levels than singletons; however, levels of IGFs were similar. In cord blood, ghrelin levels were higher in arterial than venous samples. Maternal ghrelin levels were only minimally affected by parturition, suggesting that maternal ghrelin is not involved in the transition from PGH to GH secretion. The increased arterial ghrelin levels in the foetus suggest foetal ghrelin production. Serum PGH appears to be influenced by fasting. Finally, elevated PGH levels in twin pregnancies do not appear to affect maternal IGF levels.

Kinetics and secretion of placental growth hormone around parturition

During pregnancy, placental growth hormone (PGH) is secreted into the maternal circulation, replacing pituitary GH. It is controversial whether PGH levels decline during vaginal birth. After placental expulsion, PGH is eliminated from the maternal blood. GH binding protein (GHBP) and body mass index (BMI) influence GH kinetics, but their impact on PGH kinetics is unknown. The present study was undertaken to define the kinetics of PGH during vaginal delivery and Caesarian section and to relate these kinetics to GHBP and BMI. A short term, prospective cohort study. Twelve women had repeated blood samples drawn during vaginal delivery. From 26 women undergoing planned Caesarian delivery (CS) repeated blood samples were withdrawn before, during and after the CS, allowing PGH half-life determination. During vaginal delivery, median PGH values did not change before expulsion of the placenta, although individual fluctuations were seen. Clearance of PGH from the maternal circulation was best described by a two-compartment model. The initial half-life of serum PGH was (mean +/- s.d.) 5.8 +/- 2.4 min, and the late half-life was (median) 87.0 min (range: 25.1-679.6 min). The late half-life was correlated to the pre-gestational BMI (r = 0.39, P = 0.047), but not to the serum GHBP concentration. Serum PGH did not decrease significantly during vaginal delivery. Elimination of PGH fitted a two-compartment model, with an estimated initial half-life of 5.8 min. The late phase serum half-life of PGH was related to BMI, suggesting a role for maternal fat mass in PGH metabolism.

Growth hormone binding protein and maternal body mass index in relation to placental growth hormone and insulin requirements during pregnancy in type 1 diabetic women

In pregnancy, the growth hormone axis is shifted from pituitary growth hormone (GH) to placental growth hormone (PGH). Their common binding protein, GH binding protein (GHBP), displays peak serum levels at mid-gestation in normal individuals. In the non-pregnant state, diabetes is known to be associated with elevated levels of GH and decreased levels of insulin-like growth factors (IGFs) and GHBP. Diabetes in pregnancy may therefore as well be associated with disturbances in the growth hormone axis. In the present study, we aimed at investigating the impact of GHBP and maternal body mass index (BMI) on levels of PGH, thereby enabling estimation of any association between free PGH and weight adjusted insulin requirements. In 51 type 1 diabetic women, blood samples were collected in gestational week 10+, 16+, 22+, 28+ and 34+, and analysed for their serum content of GHBP, PGH, and GH. Serum GHBP increased from the first weeks of pregnancy to median 2.07 nmol/l (range 1.17–4.26) in week 22+, then declined to median 1.29 nmol/l (range 0.77–2.35) in week 34+ (ANOVA P < 0.001). Serum PGH levels were highest in week 34+ at median 21.3 μg/l (range 5.1–165.4) ( P < 0.001), whereas a steady decrease in GH values was observed throughout pregnancy to a median 0.17 μg/l (range 0–5.53). The fraction of calculated free PGH to total PGH increased from mid-gestation onwards to 55.2% (37.0–87.1) in week 34+ at a median level of free PGH of 10.4 μg/l (range 1.9–144.0) ( P < 0.001). Similarly, the molar ratio of total PGH to GHBP increased to a maximum of 0.68 (0.12–6.62) in week 34+. As in normal pregnancies, the correlation between BMI and GHBP was lost in late pregnancy. The newborns birth weight z-score correlated with total PGH and derivatives hereof in week 34+. Neither total nor weight adjusted insulin requirements correlated to total PGH, calculated free PGH, nor GHBP. In conclusion, PGH and GHBP display a similar course during pregnancy in type 1 diabetic women as described in normal women. The well-known association between GHBP and BMI was lost in late pregnancy. Calculated levels of free PGH were positively associated to fetal growth, but not to maternal insulin requirements.

A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth.

The aim of the study was 1) to evaluate the association of maternal serum levels of placental GH and IGF-I with fetal growth, and 2) to establish reference data for placental GH, IGF-I, and IGF-binding protein-3 (IGFBP-3) in normal pregnancies based on longitudinal measurements. A prospective longitudinal study of 89 normal pregnant women was conducted. The women had, on the average, seven blood samples taken and three ultrasound examinations performed. All had normal umbilical artery pulsatility indexes during pregnancy and gave birth to singletons between 37 and 42 wk gestation with birth weights above -2 SD. Placental GH levels were detectable in all samples from as early as 5 wk gestation and increased significantly throughout pregnancy to approximately 37 wk when peak levels of 22 ng/ml (range, 4.64-69.22 ng/ml) were reached. Subsequently, placental GH levels decreased until birth. The change in placental GH during 24.5-37.5 wk gestation was positively associated with fetal growth rate (P = 0.027) and birth weight (P = 0.027). Gestational age at peak placental GH values (P = 0.007) was associated with pregnancy length. A positive association between the change in placental GH and the change in IGF-I levels throughout gestation was found in a multivariate analysis (r(2) = 0.42; P < 0.001). There was no association between placental GH and IGFBP-3 levels. The change in IGF-I throughout gestation (P = 0.039), but not placental GH, was significantly positively associated with placental weight at birth. We found a significant association between placental GH and fetal growth. In addition, we found a highly significant association between the increase in placental GH and the increase in IGF-I. The gestational age at peak placental GH levels was associated with pregnancy length.

Increase in maternal placental growth hormone during pregnancy and disappearance during parturition in normal and growth hormone-deficient pregnancies

Objective: The purpose of this study was to evaluate placental growth hormone levels in maternal circulation throughout pregnancy in normal and growth hormone-deficient women with the use of a specific assay and to determine the clearance of placental growth hormone from maternal circulation after birth. Study Design: Seventeen healthy pregnant women and 1 patient with growth hormone deficiency substituted with recombinant growth hormone during pregnancy participated in a longitudinal study from early pregnancy until birth with repetitive blood sampling and measurement of placental growth hormone levels throughout pregnancy. Furthermore, serial blood samples were drawn before, during, and after elective caesarean deliveries in 5 healthy women to calculate the half-life of placental growth hormone. Placental growth hormone was measured with the use of two monoclonal antibodies in a commercially available solid-phase iodine 125-labeled immunoradiometric assay (Biocode, Liège, Belgium). Results: Placental growth hormone levels were detectable from as early as 8 weeks of gestation in some of the women and increased throughout gestation, with a maximum at approximately 35 to 36 weeks of gestation (13.7 ng/mL; range, 5.9-24.4 ng/mL) and large interindividual variations. Placental growth hormone levels did not correlate with birth weight or placental weight. In the patient with isolated growth hormone deficiency, placental growth hormone levels were detectable from 11 weeks of gestation (3.4 ng/mL) and increased throughout pregnancy to 13.9 ng/mL, which is similar to values that are obtained in the healthy pregnant women. Substitution therapy with recombinant human growth hormone did not suppress the increase in placental growth hormone. We found a mean half-life of placental growth hormone of 13.8 minutes (range, 11.5-15.2 minutes) in healthy pregnant women and an apparently similar half-life of placental growth hormone (15.8 minutes) in the growth hormone-deficient patient, assuming a monoexponential disappearance of placental growth hormone during the first 30 minutes after the delivery. After the initial 30 minutes, approximately 75% (range, 65%-89%) of the placental growth hormone had been cleared from the maternal circulation. Conclusion: Levels of placental growth hormone in maternal circulation increase throughout pregnancy from as early as 8 weeks of pregnancy, with maximum levels around the week 35 of gestation. The pregnancy-induced rise in placental growth hormone levels in the growth hormone-deficient patient was comparable to the rise seen during normal pregnancies and was not suppressed by the concurrent human growth hormone treatment. We speculate that maternal serum levels of placental growth hormone reflect placental function and fetal growth. However, further studies are needed to evaluate the potential clinical use of placental growth hormone determinations. (Am J Obstet Gynecol 2003;188:247-51.)

Human Placental Growth Hormone—A Review

Placental growth hormone (PGH) is the product of the GH-V gene, predominantly expressed in the syncytiotrophoblast layer of the human placenta. PGH differs from pituitary growth hormone by 13 amino acids and possesses one glycosylation site. It has high somatogenic and low lactogenic activities. In the maternal circulation from 12–20 weeks up to term, PGH gradually replaces pituitary growth hormone, which becomes undetectable. PGH is secreted by the placenta in a non-pulsatile manner. This continuous secretion appears to have important implications for physiological adjustment to gestation and especially in the control of maternal IGF1 levels. PGH secretion is regulated in vitro and in vivo by glucose. Lower maternal levels of PGH are observed in pregnancies with fetal growth retardation. PGH is one example of a trophoblast hormone, which allows maternal metabolic adaptation to pregnancy. In addition, our recent data on its expression in invasive extravillous trophoblasts suggest that the physiological role of PGH might also include a direct influence of this hormone on placental development via an autocrine or paracrine mechanism.

Human placental growth hormone causes severe insulin resistance in transgenic mice

OBJECTIVE: The insulin resistance of pregnancy is considered to be mediated by human placental lactogen, but the metabolic effects of human placental growth hormone have not been well defined. Our aim was to evaluate the effect of placental growth hormone on insulin sensitivity in vivo using transgenic mice that overexpress the human placental growth hormone gene. STUDY DESIGN: Glucose and insulin tolerance tests were performed on 5 transgenic mice that overexpressed the human placental growth hormone variant gene and 6 normal littermate controls. The body composition of the mice was assessed by dual-energy radiograph absorptiometry, and free fatty acid levels were measured as a marker of lipolysis. RESULTS: The human placental growth hormone levels in the transgenic mice were comparable to those attained in the third trimester of pregnancy. These mice were nearly twice as heavy as the control mice, and their body composition differed by a significant increase in bone density and a small decrease in percentage of body fat. Fasting insulin levels in the transgenic mice that overexpressed placental growth hormone were approximately 4-fold higher than the control mice (1.57 ± 0.22 ng/mL vs 0.38 ± 0.07 ng/mL; P <.001) and 7 times higher 30 minutes after glucose stimulation (4.17 ± 0.54 ng/mL vs 0.62 ± 0.10 ng/mL; P <.0001) with no significant difference in either fasting or postchallenge glucose levels. Insulin sensitivity was markedly decreased in the transgenic mice, as demonstrated by an insignificant decline in glucose levels after insulin injection compared with the control mice, which demonstrated more than a 65% reduction in glucose levels (P <.001). CONCLUSION: Human placental growth hormone causes insulin resistance as manifested by fasting and postprandial hyperinsulinemia and minimal glucose lowering in response to insulin injection. Human placental growth hormone is a highly likely candidate to mediate the insulin resistance of pregnancy. (Am J Obstet Gynecol 2002;186:512-7.)

Serum level of placental growth hormone is raised in pregnancy rhinitis.

To describe any relationship between pregnancy rhinitis and weight gain or serum levels of estradiol, progesterone, placental growth hormone, or insulinlike growth factor I. Twenty-seven nonsmoking healthy pregnant women aged 22 to 38 years (mean age, 28 years) who had no history of respiratory allergy or chronic nasal or sinus problems volunteered to enter the study. They had no nasal complaints at entry. Nasal patency was registered daily from early pregnancy until 1 month after delivery. Nasal and oral peak expiratory flow rates were established, and the subjective blockage was scored from 0 to 4, with 0 indicating no blockage. Serum samples were collected and weight was measured on 4 occasions during pregnancy and again at the end of the study. Pregnancy rhinitis was diagnosed if the subjective nasal obstruction score was 1 or higher every morning for at least 6 weeks immediately preceding delivery, then returned to 0 within 2 weeks and remained at 0 until the end of the study. If on any day other signs of respiratory tract infection occurred, that day was excluded. Pregnancy rhinitis was diagnosed in 5 women. These 5 women showed significantly higher levels of placental growth hormone than the women without the diagnosis. No significant difference was found between the 2 groups regarding body weight or any of the other serum levels studied. Serum level of placental growth hormone is raised in pregnancy rhinitis and may be involved in its pathogeny. Pregnancy rhinitis does not significantly raise weight gain or serum levels of estradiol, progesterone, or insulinlike growth factor I.

Glucose inhibits human placental GH secretion, in vitro.

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.

Placental Growth Hormone Levels in Normal Pregnancy and in Pregnancies with Intrauterine Growth Retardation

To assess the possible role of placental growth hormone (GH) in fetoplacental growth, we measured placental and pituitary GH (GHN) in maternal plasma by means of two RIA using two MAb (5B4 recognizing both placental GH and GHN, and K24 recognizing only GHN) during pregnancy. IGF-I also was measured by RIA in the same samples after extraction. A transverse study of 186 samples obtained between 8 wk of amenorrhea (WA) and term confirmed the reported rise in GH immunoreactivity with 5B4 after 24 to 25 WA from 12.3 +/- 2.0 mU/L (mean +/- SEM) to a plateau of 27.5 +/- 3.4 mU/L at 34 to 35 WA together with the decrease in GHN to undetectable levels by 24 to 25 WA. IGF-I levels increased from 164.0 +/- 44.6 micrograms/L at 24 to 25 WA to 331.6 +/- 63.6 micrograms/L at term. A longitudinal study of 31 normal pregnant women confirmed this hormonal pattern and the reported placental GH plateau after 35 WA. A drastic decrease in placental GH was observed with the onset of labor (from 26.9 +/- 2.1 to 2.7 +/- 1.1 mU/L), whereas the decrease in IGF-I was not significant (from 212.9 +/- 26.5 to 162.4 +/- 16.9 micrograms/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of maternal IGF-I by placental GH in normal and abnormal human pregnancies.

Throughout gestation, maternal insulin-like growth factor I (IGF-I) increases progressively despite suppressed pituitary growth hormone (GH) secretion. We have previously shown that in normal pregnancy, a specific placental GH variant, rather than human placental lactogen (hPL), substitutes for pituitary GH in the regulation of maternal IGF-I. We studied the maternal IGF-I secretion in a cohort of 286 normal and abnormal pregnancies (617 blood samples). Regardless of pathology and gestational age, IGF-I values correlated with corresponding placental GH but not with hPL values. Similar correlations were evidenced for each 2-wk gestational period between 32 and 39 wk. In pathological pregnancies, when only those hormonal results that are obtained before any treatment are considered and diabetes is excluded, IGF-I levels were closely related to corresponding placental GH, but not to hPL. In women with a fetoplacental unit disorder, low placental GH levels resulted in low IGF-I and in a secondary pituitary GH increase, whereas in patients without detectable impairment of the fetoplacental unit normal placental GH corresponded to normal IGF-I. These results suggest that in pathological as well as in normal pregnancy, placental GH, and not hPL, substitutes for pituitary GH to regulate the maternal IGF-I secretion.

Placental growth hormone levels in normal pregnancy and in pregnancies with intrauterine growth retardation

Virus encoded tumor necrosis factor receptors (TNFRs) have been demonstrated to facilitate virus to escape from apoptosis or other host immune response for viral replication. Singapore grouper iridovirus (SGIV), a large DNA virus which belongs to genus Ranavirus, is a major pathogen resulting in heavy economic losses to grouper aquaculture. Here, SGIV ORF096 (VP96) encoding a putative homolog of TNFR was identified and characterized. Multiple sequence alignment indicated that SGIV-VP96 contained two extracellular cysteine-rich domains (CRDs) with conserved four or six cysteine residues, but lacked the transmembrane domain at the C-terminus. SGIV-VP96 was identified as an early (E) gene and localized in the cytoplasm in transfected or infected cells. Overexpression of SGIV-VP96 in vitro enhanced cell proliferation, and improved cell survival against SGIV infection. Furthermore, virus infection induced apoptosis and caspase-3 activity were inhibited in SGIV-VP96 expressing FHM cells compared to the control cells. Taken together, our results suggested that SGIV might utilize virus encoded TNFR like genes to modulate the host apoptotic response for effective virus replication.