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.     

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.     

Human placental growth hormone

Placental growth hormone is the product of the GH-V gene specifically expressed in the syncytiotrophoblast layer of the human placenta. Placental growth hormone differs from pituitary growth hormone by 13 amino acids. It has high somatogenic and low lactogenic activities. Assays by specific monoclonal antibodies reveal that in the maternal circulation from 15 to 20 weeks up to term placental growth hormone gradually replaces pituitary growth hormone, which becomes undetectable. It is secreted by the placenta in a nonpulsatile manner. This continuous secretion appears to have important implications for physiologic adjustment to gestation and especially in the control of maternal insulin-like growth factor-I levels. Placental growth hormone secretion is inhibited by glucose in vitro and in vivo and is significantly decreased in the maternal circulation in pregnancies with intrauterine growth restriction. Placental growth hormone does not appear to have a direct effect on fetal growth because this hormone is not detectable in the fetal circulation. However, the physiologic role might also include a direct influence on placental development through an autocrine or paracrine mechanism, as suggested by the presence of specific growth hormone receptors in this tissue.(Am J Obstet Gynecol 1997;177:1526-34.)     

Augmentation of DNA synthesis in placental and fetal tissues in utero by maternal growth hormone treatment

The influence of maternal exogenous growth hormone treatment on in utero conceptus development was evaluated in the rat. The periods of response and stimulation of DNA synthesis on embryo/fetal and placental tissues were assessed by subcutaneous injections of ovine growth hormone (oGH) preparations during pregnancy days 11-15, autopsied on day 16; and during pregnancy days 11-20 and 16-20, autopsied on day 21. To determine DNA biosynthesis potential, thymidine (methyl-3H) was administered through the jugular vein 14-16 h prior to sacrifice. DNA content and uptake of radiolabeled thymidine into DNA were analyzed for whole embryos on day 16, and for fetal liver, brain and remaining body tissues on day 21 of pregnancy. Placental tissues from oGH-treated mother and controls were also quantified for DNA content and radiolabeled thymidine uptake. oGH treatment produced a significant increase (p < 0.05) in radiolabeled thymidine uptake into DNAs of different fetal organs compared to saline-treated controls matched for weight and litter number during the latter part of gestation (fetal histogenesis period; pregnancy days 16-20). The stimulatory influence of maternal growth hormone treatment on DNA contents and radiolabled thymidine uptake on placental tissues at this period of gestation was also significantly different from that of the controls. Rat conceptus tissues (embryos and placentas) during the organogenesis period of early gestation (days 11-15) appeared to be unresponsive to such treatment. Thus, these results suggest that maternal growth hormone influences conceptus growth during the latter part of gestation and activation of placental functions may be an important aspect of stimulation of cell proliferation in the rat fetus.     

Prolactin and placental hormone levels during pregnancy in prolactinomas

Prolactin (PRL) and the placental hormones, estradiol (E2), estriol (E3), progesterone (PG), chorionic gonadotropin (HCG), and placental lactogen (HPL) were serially measured throughout pregnancy and early postpartum in three patients with prolactinomas in whom pregnancy was achieved by one of the three modalities of treatment: bromocriptine administration (patient I), irradiation of the pituitary (patient II), and human gonadotropin administration after excision of the adenoma (patient III). It was found that PRL in patient I reached the high pretreatment levels in the 2nd month of pregnancy and increased to further abnormal concentrations in the last 2 months, but fell at the onset of labor 1 week after an episode of severe headache. The PRL changes in this patient were attributed successively to tumor expansion and apoplexy. In patient II PRL decreased after irradiation, but was not normalized. During pregnancy it remained moderately increased presenting minor fluctuations. The third patient with postoperative GH and TSH pituitary insufficiency had low pretreatment PRL levels which remained practically unchanged throughout pregnancy. The two last patients gave birth to identical twins. The placental hormones were found normal in all three patients but E2 and PG were relatively increased during the last weeks of pregnancy in the twin pregnancies. Amniotic fluid and umbilical cord PRL and E2 concentrations were normal. The patients presented agalactia and suckling did not induce a PRL increase. We conclude that a) serial PRL measurements during pregnancy reflect the changes occurring in the prolactinomas and are essential in monitoring the patients bearing these tumors; b) maternal hyperprolactinemia or failure of PRL to increase during pregnancy do not influence either the secretion of placental hormones or PRL concentration in amniotic fluid and the newborn; and c) hyperprolactinemia during pregnancy is of maternal pituitary origin.     

Growth hormone levels in maternal serum during pregnancy

Maternal growth hormone (GH) levels during pregnancy have been variously reported to be suppressed or, more lately, to be increased. In an attempt to clarify this point, maternal GH levels were estimated with two modern GH polyclonal radio-immunoassays (RIAs) and a new monoclonal enzyme-linked immunoassay (ELISA). The Cambridge Medical Diagnostics RIA and the more specific bioMérieux RIA gave similar results in control non-pregnant patients with raised GH levels, while the monoclonal ELISA gave slightly lower values. The bioMérieux assay gave results about 10 times higher than the Cambridge assay during pregnancy, at 12-61 ng/ml at 16-20 weeks and 47-153 ng/ml at 28-39 weeks (total n = 27). These high 'GH' levels did not correlate with maternal levels of prolactin or human placental lactogen. It is presumed that some unknown GH-like molecule(s) are being estimated in this assay, possibly the recently discovered human chorionic GH. That this is not pituitary GH was confirmed by the monoclonal ELISA, by which GH levels were almost undetectable during pregnancy.     

Role of maternal prolactin in early pregnancy failure

To study the significance of maternal prolactin (PRL) secretion in early pregnancy failures, intravenous thyrotropin-releasing hormone (TRH) stimulation tests were carried out in 39 women with normal or doomed early pregnancy, as verified by ultrasound examination, before the onset of clinical symptoms of abortion. The basal PRL levels did not differ between the women with normal early pregnancy (N = 15), blighted ovum (N = 13), or with missed abortion (N = 11). Thyrotropin-releasing hormone injection stimulated PRL secretion in all cases, but the response was smaller (P less than .01) in women with early pregnancy failure. It is concluded that PRL is not significant in the etiology or course of early pregnancy wastage and that its basal or stimulated measurement is of limited value in the prediction of pregnancy outcome.     

Maternal plasma, human placental lactogen, alpha-fetoprotein, prolactin and growth hormone in early pregnancy

Human placental lactogen (HPL), alpha-fetoprotein, prolactin and growth hormones were assayed simultaneously twice weekly in 21 women from 4--16 weeks' gestation. Mean levels were established from 15 of the women for comparison with one woman with a twin pregnancy, two who aborted and three who received progestogen supplements. There was wide interpatient variation in all hormone levels excepting HPL. The mean levels of all except growth hormone showed an upward trend. Mean growth hormone levels were higher initially but remained within a 2--4 ng/ml range throughout. In the twin pregnancy, only HPL and alpha-fetoprotein levels were significantly raised. HPL was detected in one of the two women who aborted, whereas growth hormone was initially extremely high, falling precipitously prior to abortion in both women. Treatment with progestogen supplements did not appear to influence any of the hormones measured. This study suggests that serial estimations of HPL appear to be the most cost-effective guide to early fetal well-being of the four hormones measured.     

胎盘细胞凋亡与胎儿生长受限关系的研究

目的　探讨胎盘细胞调亡与胎儿生长受限 (FGR)发生的关系。方法　应用透射电镜和DNA缺口末端标记法检测 18例FGR患者 (FGR组 )及 14例正常妊娠妇女 (正常妊娠组 )的胎盘细胞凋亡情况。同时观察两组的胎盘重量及新生儿平均出生体重。结果　FGR组胎盘凋亡细胞核比率为12 1‰ ,电镜下凋亡细胞核呈明显致密状 ,染色质结块 ,胎盘平均重量为 (2 3 6± 2 4)g ,新生儿平均出生体重为 (2 0 71± 42 8)g;正常妊娠组胎盘凋亡细胞核比率为 7 3‰ ,胎盘平均重量为 (3 5 4± 63 )g ,新生儿平均出生体重为 (3 411± 5 88)g。FGR组胎盘凋亡细胞核比率明显高于正常妊娠组 (P <0 0 5 )。结论　胎盘细胞凋亡增加与FGR的发生有关     

Effects of human growth hormone upon term placental hormone secretion in vitro

The role of human growth hormone (hGH) on placental hormone secretion at term was investigated in two in vitro models: placental explants and cultured trophoblastic cells. Physiological concentrations of hGH caused a significant dose-dependent increase in placental lactogen and progesterone secretion. In the explant model it stimulated estradiol secretion. In order to determine whether this stimulatory effect on estradiol is exerted via aromatase, an isolated cell culture was utilized where androstenedione was supplied as substrate. In this model, hGH exerted a mild inhibitory effect. In conclusion, hGH at levels present in the fetal circulation exerts a significant stimulatory effect upon placental function as reflected by both peptide and steroid hormone production and secretion. The effect of estradiol secretion is the end result of an inhibitory effect on androgen aromatization and a stimulatory effect on earlier steps.     

Immunoreactive gonadotropin-releasing hormone level in maternal circulation throughout pregnancy

Immunoreactive gonadotropin-releasing hormone was quantitated in maternal blood. Circulating levels of gonadotropin-releasing hormone were found to be significantly higher during pregnancy than in nonpregnant cycling women. The highest concentrations of gonadotropin-releasing hormone immunoreactivity were observed in the first half of pregnancy with values at 20 to 42 weeks being significantly lower. A correlation with placental human chorionic gonadotropin-releasing hormone concentrations and maternal circulating gonadotropin-releasing hormone levels was noted. Four pregnancies that resulted in premature labor and/or delivery had very low circulating maternal gonadotropin-releasing hormone concentrations, possibly reflecting placental dysfunction in these cases.     

Scintigraphic studies of uterine and placental growth and placental migration during pregnancy

Placental scintigraphy with 113mIn (Indium) combined with cervical marking with a shielded 57Co (Cobalt) radioactive source was used to study uterine and placental growth in human pregnancy and placental location and migration in a total of 176 patients. Uterine length measurements can be used for selecting growth retarded fetuses. There was an approximately constant ratio between placenta diameter and uterine length (0.68 +/- 0.03). When the placenta was located on the ventral uterine wall, low implantation occurred in 61%. The corresponding figure for low implantation when the placenta was located on the dorsal uterine wall was 30%. The difference was highly significant. Placental migration was studied in 20 patients. Significant migration occurred in 11 cases. The placental margin closest to the internal cervical os migrated outwards about 3 cm on average.     

高龄孕妇子痫前期并发胎盘早剥妊娠结局分析

目的 探讨高龄对子痫前期并发胎盘早剥母儿结局的影响.方法 回顾性分析2017年1月至2019年12月在广州医科大学附属第三医院住院分娩的子痫前期并发胎盘早剥、单胎妊娠患者40例,以年龄≥35岁者为高龄组(14例),年龄<35岁者为对照组(26例),比较两组患者的临床资料特点、生化指标及围产儿结局.结果(1)两组孕妇一般...