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Placental hormones as possible markers in gynaecological cancer.

Two placental hormones (human chorionic gonadotropin and human chorionic somatotropin) were assayed in serum of patients bearing a wide variety of malignant tumours. The incidences of these hormones were found to be higher among female patients. Further studies revealed that the incidence was high in patients with malignant tumours of the gonads, breast, uterus and cervix. It was shown that these hormones are the products of tumour cells and that they are released in circulation. Studies on cervix cancer suggest that they may be useful aids in following the course of therapy.

Adult↗

Relation between maternal haemoglobin and placental hormone concentrations in early pregnancy.

Environmental factors that influence placental development are of particular interest because of the reported association between adult hypertension, low birthweight, and large placental size. Maternal anaemia is one environmental factor that is associated with an increase in placental size at birth. We have examined the relation between haematological status and plasma concentrations of chorionic gonadotropin (hCG) and placental lactogen (hPL) in 175 women at about 10 weeks of pregnancy. There were significant negative correlations between maternal haemoglobin concentration and the levels of hCG (p = 0.03) and hPL (p = 0.02). Although 21% of women had low iron stores (ferritin < 13 micrograms/L), no relation was found between serum ferritin and the two placental hormones. There was no association between plasma volume (calculated from maternal weight and height) and hCG or hPL concentrations. We conclude that our observations reflect an influence of the maternal environment on the placenta. The fact that negative correlations with placental hormone concentrations exist across the normal haemoglobin range suggest that they reflect a normal aspect of placental development. We speculate that placental growth is, in part, determined by maternal factors that prevail before conception. One possibility is that these factors modify angiogenesis within the trophoblastic villi.

Adolescent↗

In vitro influence of some mammalian pituitary and placental hormones on androgen production by the lizard testis.

Effect of mammalian pituitary and placental hormones has been studied on in vitro androgen production by the testis of the spiny-tailed lizard, Uromastix hardwicki. Aliquots of pooled testicular tissue from adult lizards were incubated individually with 1 microgram each, of oFSH, oLH, oTSH and 1 IU each of hCG, PMSG, and ACTH. Androgen was measured by testosterone radioimmunoassay in both the tissue and the incubation medium. Severalfold increase in androgen production was observed in the testicular tissue incubated with FSH, LH, TSH nd PMSG. Maximum stimulation was obtained with FSH. hCG also caused a measurable increase in androgen production but was much less potent than PMSG. Incubation of testicular tissue with ACTH did not result in a significant change in androgen production as compared to the controls. The hormonal specificity for steroidogenesis by the lizard testis has been discussed in the light of these results.

Androgens↗

Two placental hormones are agonists in stimulating megakaryocyte growth and differentiation.

Previously, we demonstrated that a placental hormone, PRL-like protein E, stimulates megakaryocyte growth and differentiation. We now find that PRL-like protein E and a second placental hormone, PRL-like protein F (PLP-F), bind the same receptor. PLP-F, which is produced later in pregnancy, might therefore act as either an agonist or antagonist of PRL-like protein E. To resolve this question, we produced recombinant PLP-F in mammalian cell cultures, purified the secreted glycoprotein hormone, and determined its activity in primary mouse bone marrow cultures. PLP-F induces megakaryocyte differentiation and megakaryocyte progenitor growth in a dose-dependent manner, with significant activity detected at a concentration as low as 50 ng/ml. PLP-F in maternal serum reaches at least 1 micro g/ml on gestational d 14.5, and thus the biological activity of PLP-F is detected at physiological concentrations. These results show that PRL-like proteins E and F have the same stimulatory effects on megakaryocyte growth and differentiation, and therefore represent gestation stage-specific agonists.

Animals↗

Antifertility actions of the progesterone antagonist RU 486 include direct inhibition of placental hormone secretion.

the antifertility effects of the potent antiprogestin RU 486 (mifepristone) during early pregnancy have been attributed to its blockade of progesterone receptors in the endometrium. Studies in cultured syncytiotrophoblasts have revealed an additional action of RU 486 at the placental level, where it impairs the production of human chorionic gonadotropin (hCG), human placental lactogen (hPL), and progesterone. RU 486 (10 nmol-10 mumol/l) attenuated the production of all three placental hormones, in a dose-related manner, and its effects on hCG and hPL were reversed by addition of exogenous progesterone. The specific inhibitory effects of RU 486 on placental hormone secretion indicate that its antifertility actions are attributable to competitive inhibition of progesterone action in the trophoblast as well as in the endometrium.

Abortifacient Agents↗

Effects of glucose on placental hormones in the human term placenta in vitro.

Glucose intake during pregnancy results in a decrease in endogenous insulin-like growth factor binding protein-1 (IGFBP-1). However, the exact role of glucose on placental secretion of IGFBP-1 is unclear. This study was designed to investigate the direct effects of glucose on the production of IGFBP-1 and other placental hormones, using an isolated placental preparation. Using the dual recirculating perfusion system for an isolated human placenta lobule, a total of 43 experiments were performed over a duration of 6 hours. Twenty placentae were perfused with a medium containing 141 +/- 10 mg/dL (7.83 +/- 0.56 mmol/L) glucose (group I) and 23 placentae with 242 +/- 12 mg/dL (13.43 +/- 0.67 mmol/L) glucose (group II). Levels of insulin, glucose, lactate, insulin-like growth factor (IGF-I), IGFBP-1, human placental lactogen (hPL) and beta-human chorionic gonadotropin (beta-hCG) were measured at 30 minute intervals during perfusion. Insulin and IGF-I were barely detectable in the perfusates and their levels were not modulated by glucose. IGFBP-1 was predominantly detected in the maternal rather than the fetal compartment of the placental circulation. Glucose increased the levels of IGFBP-1 in the maternal circulation in groups I and II during the first two hours of perfusion (188 +/- 58% and 193 +/- 31%, respectively). However, during the subsequent 4 hour period, the increase in IGFBP-1 concentration was significantly higher in group II (926 +/- 427%) than in group I (428 +/- 216%) (p < 0.05). There was no difference in the levels of hPL or beta-hCG between the two groups in the maternal circulation. Thus, glucose stimulates the production of IGFBP-1 in the maternal circulation of a placenta in vitro. This increase in IGFBP-1 by glucose in vitro, as opposed to the decrease of IGFBP-1 in vivo, may be due to a lack of circulatory maternal insulin in the isolated placental preparation. These results also suggest that there may be a functional barrier within the placenta that prevents an increase in the level of IGFBP-1 in the fetal circulation.

Chorionic Gonadotropin, beta Subunit, Human↗

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.

Growth Hormone↗

Placental hormones, nutrition, and fetal development.

Fetal growth retardation due to maternal malnutrition is widespread especially in the Third World. Little is known about the mechanisms that regulate the growth of the fetus and placenta during protein malnutrition. It is known that the placental size and levels of circulating placental hormones such as human chorionic gonadotrophins (hCG), human placental lactogen (hPL), and estrogens are affected by the nutritional status of the mother. There is suggestive evidence that during malnutrition, hPL may increase lipolysis and exert a glucose sparing effect in the mother, thereby promoting glucose availability to the fetus. We have studied the influence of dietary protein deficiency on the binding of dexamethasone to the specific cytosol receptors in adult and fetal tissues. A low protein diet in adult male rats is associated with a decrease in dexamethasone binding to liver cytosol receptors. On the other hand, protein deprivation in pregnant female rats leads to an increase in dexamethasone binding to liver cytosol receptors of both the mother and fetus. However, the influences of maternal protein deprivation on dexamethasone receptors in the fetal liver and lungs are not similar. At 21 days gestation the binding of dexamethasone to fetal lung receptors of protein-deficient mothers is lower than that in the controls. These differences at a critical time in the fetal lung development indicate that a fall in receptors for dexamethasone may lead to impaired phospholipid synthesis in fetuses of protein-deficient mothers and point to the importance of nutritional factors in the biochemistry of fetal development.

Animals↗

Ectopic production of placental hormones (human chorionic gonadotropin and human placental lactogen) in carcinoma of the uterine cervix.

Serum hCG and hPL levels were assayed simultaneously in patients with cervical carcinoma and were compared with those of a miscellaneous group of malignant conditions. It is apparent from the results that hCG secretion is of a much wider occurrence as compared to hPL. There seems to be a definite relationship between the clinical staging and ectopic hCG and hPL production. While hCG secretion is predominant in the later stages, hPL is produced in the earlier stage. It therefore seems that hPL might prove to be helpful in early diagnosis of carcinoma of the uterine cervix.

Adenocarcinoma↗

Fetal tissue can synthesize a placental hormone. Evidence for chorionic gonadotropin beta-subunit synthesis by human fetal kidney.

Metabolically active tissues from second trimester human fetuses were examined for their ability to synthesize the placental hormones chorionic gonadotropin and chorionic somatomammotropin. During short-term incubation studies both placenta and fetal kidney were found to synthesize and secrete the beta-subunit of chorionic gonadotropin, whereas its synthesis was not observed in fetal liver, lung or muscle. In addition, chorionic somatomammotropin synthesis and secretion was demonstrated with placental tissue but could not be detected in any of the fetal tissues examined. These observations constitute the first evidence that the genome of a fetal tissue directs the synthesis of what is considered a placental hormone.

Chorionic Gonadotropin↗

Release of prorenin and placental hormones from superfused minced chorion laeve.

SUBJECT: Prorenin, the biosynthetic precursor of renin, is present in organs of the human reproductive system. METHOD AND MATERIAL: In this study we tested whether the release of prorenin from superfused minced human chorion laeve tissue is related to that of other placental hormones. We also investigated whether intracellular second messenger systems are involved in the prorenin release from placental tissue. RESULTS: More than 95% of the total renin released was in the form of prorenin. The release pattern of human chorionic gonadotropin (hCG), estradiol and progesterone was similar to that of prorenin. Exogenous hCG, the estrogen receptor blocker tamoxifen and the progesterone receptor blocker RU 486, 8-bromo cyclic AMP, diltiazem and angiotensin II did not affect prorenin release. CONCLUSION: We conclude that prorenin, not active renin, is released from placental cytotrophoblastic tissue. This release occurs in parallel to that of other placental hormones but it is not regulated by steroid receptors, hCG, intracellular calcium or cyclic AMP.

Analysis of Variance↗

Estradiol-17 beta and 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one production by isolated ovarian follicles of amago salmon (Oncorhynchus rhodurus) in response to mammalian pituitary and placental hormones and salmon gonadotropin.

The effects of mammalian pituitary and placental hormones and dibutyryl cyclic AMP (cAMP) on the production of estradiol-17 beta and 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17 alpha, 20 beta-diOHprog) by amago salmon (Oncorhynchus rhodurus) ovarian follicles in vitro were compared with partially purified chum salmon (Oncorhynchus keta) gonadotropin (SGA). Estradiol-17 beta production was examined using midvitellogenic ovarian follicles; SGA was the most effective hormone tested; at a dose of 1 microgram/ml it stimulated the production of approximately 4 ng/ml estradiol-17 beta. Ovine LH (o-LH) was about 0.5% as effective as SGA. Taking into account the relative purity of the preparations used, ovine FSH (o-FSH) was almost as effective as o-LH. Both HCG and bovine TSH (b-TSH) stimulated estradiol-17 beta production at high doses. Porcine ACTH (p-ACTH), ovine GH (o-GH), and ovine PRL (o-PRL) induced very modest increases in estradiol-17 beta; cAMP was highly effective. 17 alpha, 20 beta-DiOHprog production was examined using full-grown immature oocytes which were capable of maturing in vitro in response to 1 microgram/ml SGA. o-LH was about 0.5% as effective as SGA. o-FSH, b-TSH, and HCG appeared to be less effective in stimulating 17 alpha, 20 beta-diOHprog production, compared to estradiol-17 beta. o-GH and o-PRL induced marginal increases in production and p-ACTH had a very modest inverse dose-response effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Stanniocalcin (STC) in the endometrial glands of the ovine uterus: regulation by progesterone and placental hormones.

Stanniocalcin (STC) is a hormone in fish that regulates calcium levels. Mammals have two orthologs of STC with roles in calcium and phosphate metabolism and perhaps cell differentiation. In the kidney and gut, STC regulates calcium and phosphate homeostasis. In the mouse uterus, Stc1 increases in the mesometrial decidua during implantation. These studies determined the effects of pregnancy and related hormones on STC expression in the ovine uterus. In Days 10-16 cyclic and pregnant ewes, STC1 mRNA was not detected in the uterus. Intriguingly, STC1 mRNA appeared on Day 18 of pregnancy, specifically in the endometrial glands, increased from Day 18 to Day 80, and remained abundant to Day 120 of gestation. STC1 mRNA was not detected in the placenta, whereas STC2 mRNA was detected at low abundance in conceptus trophectoderm and endometrial glands during later pregnancy. Immunoreactive STC1 protein was detected predominantly in the endometrial glands after Day 16 of pregnancy and in areolae that transport uterine gland secretions across the placenta. In ovariectomized ewes, long-term progesterone therapy induced STC1 mRNA. Although interferon tau had no effect on endometrial STC1, intrauterine infusions of ovine placental lactogen (PL) increased endometrial gland STC1 mRNA abundance in progestinized ewes. These studies demonstrate that STC1 is induced by progesterone and increased by a placental hormone (PL) in endometrial glands of the ovine uterus during conceptus (embryo/fetus and extraembryonic membranes) implantation and placentation. Western blot analyses revealed the presence of a 25-kDa STC1 protein in the endometrium, uterine luminal fluid, and allantoic fluid. The data suggest that STC1 secreted by the endometrial glands is transported into the fetal circulation and allantoic fluid, where it is hypothesized to regulate growth and differentiation of the fetus and placenta, by placental areolae.

Animals↗

Physiological role of human placental growth hormone.

Placental growth hormone (PGH) is the product of the GH-V gene specifically expressed in the syncytiotrophoblast layer of the human placenta. PGH differs from pituitary growth hormone by 13 amino acids. It has high somatogenic and low lactogenic activities. Assays of PGH by specific monoclonal antibodies reveal that in the maternal circulation from 15-20 weeks up to term, PGH gradually replaces pituitary growth hormone which becomes undetectable. It 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 inhibited by glucose in vitro and in vivo, and is significantly decreased in the maternal circulation in cases of pregnancies with intrauterine growth retardation. PGH does not appear to have a direct effect on fetal growth, as this hormone is not detectable in the fetal circulation. However the physiological role of PGH might also include a direct influence on placental development via an autocrine or paracrine mechanism as suggested by the presence of specific GH receptors in this tissue.

Cell Differentiation↗

Immunohistochemical demonstration of placental hormones in the diagnosis of uterine versus ectopic pregnancy.

The authors find that immunohistochemical demonstration of placental hormones in endometrium is useful in the identification of trophoblast independent of the presence of chorionic villi. Human chorionic gonadotropin (HCG) and human placental lactogen (HPL) are markers for trophoblastic cells. The markers were studied in 21 cases of gestational endometrium without villi in which the clinical differential diagnosis was ectopic pregnancy versus missed or incomplete uterine abortion. Trophoblastic cells were identified in four cases by routine microscopy and in an additional seven cases using the markers. In none of these cases was there a subsequent demonstration of ectopic pregnancy. In six of the ten negative cases, ectopic pregnancies subsequently were removed. Thus, the use of these hormone markers in endometrial specimens increases precision in the diagnosis of uterine versus ectopic pregnancy.

Abortion, Incomplete↗

[Observations on the development of pregnancy in women with epilepsy based on analysis of protein placental hormones and alpha fetoprotein].

In 19 women with epilepsy the radioimmunoassay determinations in the serum were carried out of human chorionic gonadotropin (HCG), chorionic somatotropin (HPL) and alpha-fetoprotein. The concentrations of placental hormones were not abnormal, but from the 15th week on a rise in AFP level was observed. In the group with raised AFP level the patients received higher doses of phenytoin. In some cases the AFP level exceeded severalfold that in healthy women. One woman with raised AFP gave birth to a premature newborn which died on the 3rd day, another newborn in this group had congenital anomalies (cerebral hygromas). Although placental dysfunction was not observed in this group, but considering a high proportion of surgical interventions during labour (20%) and raised AFP level, pregnancy in epileptic women should qualify them into high-risk pregnancies requiring particular obstetric care.

Adult↗