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PubMed1984

A quantitative relationship between conceptus number and ovarian steroid dehydrogenase activity in pregnant rats.

The effects of a conceptus-derived substance on the activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-HSD in the ovary were studied in the rat. On day 7 of pregnancy (day 1 = insemination), rats were laparotomized and the desired number of conceptuses was aspirated from the uterus; thus, rats carrying one, two, three, four, five to seven or eight to ten conceptuses were prepared. They were autopsied on day 15 and 3 beta-HSD and 20 alpha-HSD activity in the corpus luteum (CL) or non-luteal ovarian tissue ( NLO ) was determined. Conceptus number was directly related to 3 beta-HSD and inversely related to 20 alpha-HSD activity in the CL. The serum progesterone level and CL weight were also directly related to conceptus number. Neither 3 beta-HSD nor 20 alpha-HSD activity in the NLO was affected by conceptus number. These results indicated that 3 beta-HSD and 20 alpha-HSD in the CL are probably regulated by placental hormone secreted in proportion to the number of conceptuses; in the NLO these enzymes may be controlled by a different mechanism.

20-Hydroxysteroid Dehydrogenases↗
PubMed1993

Ontogeny and characterization of epidermal growth factor receptors on the fetal area of the sheep placenta.

Studies of the binding of 125I-labelled epidermal growth factor (EGF) to the ovine placenta were carried out on days 50, 90-100 and 140 of pregnancy. Membrane fractions were purified from the fetal area of the cotyledon. Two classes of binding sites were found. Their dissociation constants (Kd) were not significantly different for the three stages of pregnancy considered (high-affinity Kd 54-70.2 pmol/l; low-affinity Kd 12.2 to 19 nmol/l). However, the number of high-affinity binding sites on days 90-100 was significantly (P < 0.01) greater (146 +/- 19 fmol/mg protein) than on either day 50 or day 140 (respectively 74.2 +/- 1.26 and 56.3 +/- 5.6 fmol/mg protein). Affinity cross-linking studies followed by SDS-PAGE under reducing conditions demonstrated that the major part of the EGF was specifically cross-linked to a protein of molecular weight of 150 kDa and to lesser extent to 180 kDa and 130 kDa proteins. Membranes prepared from unfrozen tissues, in the presence of sodium iodoacetate to reduce endogenous enzymatic conversion of the 180 kDa form to the 150 and 130 kDa forms, still exhibited a major EGF-binding protein of 150 kDa. The occurrence of an increased number of EGF receptors at the period of rapid cotyledonary growth which coincides with the increase in placental hormonal secretions suggests that EGF has a role in the development of the ovine placenta.

Animals↗
PubMed1996

Attenuation of human chorionic gonadotropin release by nitric oxide in choriocarcinoma cell lines.

Nitric oxide (NO) is involved in the regulation of endocrine functions, but only a few studies have been reported about its role in placental hormone secretion. We investigated whether NO has any function in the release of human chorionic gonadotropin (hCG) in two different choriocarcinoma cell lines, JEG-3 and BeWo. First, nitric oxide synthase (NOS) was characterized in the choriocarcinoma cells. NOS activity was localized mainly in the particulate fraction and depended on calcium/calmodulin. Activity was inhibited by the presence of the L-arginine analog, NG-monomethyl-L-arginine (L-NMMA; 1 x 10(-4) M). Western blot analysis showed that the choriocarcinoma cells contained an endothelial isoform of NOS. The NO donor, sodium nitroprusside (SNP; 1 x 10(-5) and 1 x 10(-4) M), significantly inhibited hCG secretion in both choriocarcinoma cell lines. The suppression of hCG release by SNP (1 x 10(-5) M) was blocked by the addition of an NO scavenger, hemoglobin (1 x 10(-6) M). L-Arginine (1 x 10(-2) M), a NOS substrate, inhibited basal hCG secretion in JEG-3 cells. Incubation of the cells with L-NMMA (1 x 10(-4) and 1 x 10(-3) M) significantly increased hCG release. Exposure of both cell lines to increasing concentrations of a cyclic GMP analog (8-bromo-cyclic GMP; 1 x 10(-4) to 1 x 10(-2) M) caused a dose-dependent inhibition of hCG release. Cyclic GMP accumulation in response to SNP (1 x 10(-4) M), however, was not detected in either JEG-3 or BeWo cells. These data demonstrated that the endothelial isoform of NOS and a functional L-arginine-NO pathway are present in the choriocarcinoma cell lines. In addition, these findings support the hypothesis that NO produced in these cell lines is involved in the regulation of hCG secretion. We assume that although cyclic GMP is likely to play a role as a second messenger, a cyclic GMP-independent pathway cannot be excluded as a possible physiological mechanism in the attenuation of hCG release by NO.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1975

Comparison between prostaglandin E2 and oxytocin actions on pregnant mouse myometrium.

Effects of prostaglandin E2 (PGE2) and oxytocin on the membrane activity of pregnant mouse myometrium were investigated with the microelectrode method. Sensitivity of the myometrium to oxytocin increased only during the last stage of gestation, however sensitivity to PGE2 gradually increased beginning at the middle stage of gestation. Prolonged treatment with PGE2 but not with oxytocin produced desensitization of the myometrium. When the membrane potential was electrically displaced to the resting level after the membrane had been markedly depolarized by either PGE2 or oxytocin, spike activity was restored. However with PGE2 there was continuous spike generation and with oxytocin periodic burst discharges with silent periods. In Ca-free Locke solution, PGE2 and oxytocin still produced depolarization of the membrane, however, oxytocin produced larger depolarization. The different responses of the membrane to PGE2 and oxytocin are discussed in relation to the roles of Ca ion and to the ovarian and placental hormones during gestation.

Animals↗
PubMed1993

Normal ovaries in neonates and infants: a sonographic study of 77 patients 1 day to 24 months old.

OBJECTIVE: Normal values for ovarian measurements in adults have been revised over the past decade. A recent report stated that ovarian cysts were common in healthy girls 2-13 years old, refuting the findings of a 1984 study. No large sonographic study of normal ovaries in girls 1 day to 24 months old has been performed. We evaluated ovaries in girls in this age group to determine the normal volume and prevalence of ovarian cysts. SUBJECTS AND METHODS: The ovaries of 77 consecutive patients 1 day to 24 months old were evaluated during routine pelvic sonography. Patients were divided into three age groups: 1 day to 3 months old (when gonadotropin levels are highest because of loss of placental hormonal influence), 4-12 months old (an intermediate group), and 13-24 months old (when gonadotropin levels are low). RESULTS: Ninety-eight ovaries were imaged in three dimensions. The mean volume was 1.06 cm3 (range, 0.7-3.6 cm3) among girls up to 3 months old; 1.05 cm3 (range, 0.2-2.7 cm3) among girls 4-12 months old; and 0.67 cm3 (range, 0.1-1.7 cm3) among girls 13-24 months old. We found no significant difference in mean volumes among the three groups. The prevalence of ovarian cysts was similar in all three groups; ovarian cysts were seen in 84% of all imaged ovaries. Macrocysts (cysts larger than 9 mm) were seen in 18% of all cystic ovaries. CONCLUSION: Ovaries of girls 1 day to 24 months old can have volumes greater than 1 cm3. Ovarian cysts are common. Macrocysts can be seen despite claims that they are rare in girls less than 11 years old.

Analysis of Variance↗
PubMed2001

Diagnosing neonatal female genital anomalies using saline-enhanced sonography.

OBJECTIVE: The purpose of this article is to show the usefulness of sonography in diagnosing genital anomalies early in female neonates who have unilateral renal malformations. Our patients were three female neonates with renal anomalies that had been detected in utero. We performed sonography of the inner genitalia of each girl after filling the vagina with saline solution. In two patients with multicystic dysplastic kidney disorder, the examination revealed uterus didelphys with obstruction of one of the vaginas. Sonographic examination of the third patient showed Gartner's duct cyst with renal agenesis. CONCLUSION: The neonatal period provides a unique opportunity to use sonography to detect uterine anomalies because maternal and placental hormone stimulation increases the size of the uterus. Simultaneous intravaginal saline instillation during imaging further improves the radiologist's ability to diagnose genital malformations precisely. This procedure is a simple, sensitive, and inexpensive examination method that is useful in imaging female neonates with renal dysplasia or agenesis detected in utero or in the neonatal period. Its particular value is to further characterize a cystic mass posterior to the bladder that is seen at transabdominal sonography.

Abnormalities, Multiple↗
PubMedDate not supplied

Relative sensitivity of postpartum gestational diabetic women to oral contraceptive agents and other metabolic stress.

Women who develop diabetes mellitus during pregnancy very often revert to normal carbohydrate metabolism after parturition. During this quiescent period, however, increased sensitivity to adverse metabolic stress is evident. Recurrence of impaired carbohydrate tolerance with greater frequency than in normal populations is observed following the administration of oral contraceptive agents, glucocorticoids, and certain placental hormones such as human chorionic somatomammotropin. Factors responsible for this vulnerability to adverse stress are unknown but, in part, may reside in subclinical defects in beta-cell function. Ultimately, the great majority of these individuals develop permanent disease, suggesting that diabetes initially manifested only during pregnancy is not transient but progresses to more severe forms later in life.

Blood Glucose↗
PubMed1999

Tissue expression of the S100 protein family-related MRP8 gene in human chorionic villi by in situ hybridization techniques.

The present study examined the tissue-expression of MRP8 in human placenta using a biotinylated DNA-probe for in situ hybridization. During the first and second trimesters high level and synchronous expression of MRP8 was detected in cytotrophoblasts (Langhans' cells), placental-tissue macrophages (Hofbauer cells), fibroblast-like cells, endothelial cells and monocytic lineages in the foetal capillaries. The highest expression was seen in large and oval-shaped cytotrophoblasts and stromal-cell populations at around 8-11 weeks. At term placentas had low level MRP8 expression chiefly in the myelomonocytic lineages in foetal blood vessels. The peripheral monocytes in the maternal space also expressed MRP8 at high levels during the first and second trimesters, which subsequently decreased at term. We suggest three hypotheses based on these results; (1) The initial expression of MRP8 may occur in two cell lineages of extra-embryonic and intra-embryonic origin in the first two trimesters; (2) the cytotrophoblasts, placental-tissue macrophages and fibroblasts may play important roles in the production of placental hormones and the immuno-regulation of foetal acceptance; and (3) MRP8-expression may be synchronously inhibited once the trophoblasts and stromal cell-constituents have differentiated in the chorionic villi.

Antigens, Differentiation↗
PubMed1989

Placental protein distribution in maternal diabetes mellitus: an immunocytochemical study.

Placentas associated with maternal diabetes are generally characterized by features of villous immaturity. We correlated the villous histology with the immunocytochemical distribution of four trophoblastic proteins: beta human chorionic gonadotropin (beta HCG), placental alkaline phosphatase (PLAP), pregnancy specific beta-1-glycoprotein (SP1), and human placental lactogen (HPL) in 14 third-trimester placentas associated with diabetes mellitus. Staining was increased for beta HCG and decreased for PLAP, SP1, and HPL in the diabetic placentas compared to control placentas of similar gestational age. This pattern was most prominent in areas of marked architectural villous immaturity within individual placentas and suggests concomitant functional immaturity.

Alkaline Phosphatase↗
PubMed1977

Effect of pregnancy on lactation in mice.

Albino mice were used to test the effect of simultaneous pregnancy on lactation in successive lactations. Weights of litters were used to estimate lactational performance by standardizing litters at eight pups on day 1 postpartum and weighing pups immediately after a normal nursing period on days 10, 14 and 20 of lactation. Eight dams were used in each of two treatments:lactating-nonpregnant and lactating-pregnant. Dams were sibling pairs for each treatment to reduce variation. Dams that were simultaneously pregnant and lactating had heavier litters on day 20 of the first lactation and on days 14 and 20 of the second lactation as compared to their lactating-nonpregnant siblings. The results imply that pregnancy provides a stimulus to concurrent and sucessive lactation in the mouse. This may be due to the effect of placental hormones on delaying mammary involution or on maintaining high milk synthesis past day 10 of lactation.

Animals↗
PubMedDate not supplied

[How to stimulate the placental function (author's transl)].

Imminent abortion, habitual abortion and threatened premature labor, all constitute difficult clinical problems. Those cases require on every occasion a diagnosis as acurate as possible, and unfortunately our present methods of biochemical determinations only represent a means to evaluate placental function. On those cases where a faulty placental function is detected thru the tests presently available, the authors recommend the utilization of a placentotropic substance, Gestanon, that is capable to stimulate and normalize the placental function, a is demostrated by the statistical results published in the international medical bibliography.

Abortion, Habitual↗
PubMedDate not supplied

[Immunological mechanisms involved in the pathogenesis of multiple sclerosis].

OBJECTIVE: To summarize current knowledge of the immunological mechanisms involved in the pathogenesis of multiple sclerosis and its implications in the development of new therapeutic options. DEVELOPMENT: The aetiology of multiple sclerosis is still not completely clear. Nevertheless there is much evidence in favor of the possibility that autoimmune phenomena play an important part in the development and course of the disorder. Knowledge of the immunological phenomena involved determines the possibility of modifying the immune response at different levels. Thus it is possible to act on: 1. The trimolecular complex during lymphocyte activation. 2. To block the passage of activated cells across the blood-brain barrier. 3. To modify the effector action of specific antigen cells, and 4. Induce populations of regulator cells. Similarly, immunological phenomena which develop during pregnancy and the postpartum period are an interesting physiological model which permit identification of the mechanisms by which autoimmune disorders are modified. Amongst the factors affecting the immune response during pregnancy and the postpartum period the various maternal and foeto-placental hormones should be considered. Their actions may be due to their effects on the secretion of different groups of cytokines. Better understanding of the factors regulating the immune response during pregnancy and the postpartum period permits definition of new potential sites for therapeutic action. CONCLUSIONS: Current knowledge of the many physiopathological mechanisms involved in the development of multiple sclerosis allows rational development of new alterative treatments for this condition.

Blood-Brain Barrier↗
PubMed1979

[Ontogenesis of hypothalamic control of adenohypophyseal secretions in the human foetus (author's transl)].

The endocrine glands of the human foetus are active early in gestation, and various foetal and placental hormonal contributions are essential for growth and sexual differentiation. 1. The anterior pituitary gland has the ability to synthesize, store and secrete hormones early in gestation. The patterns of change in plasma concentrations of hGH (Fig. 1), ACTH, LH and FSH (Fig. 2) during gestation indicate that secretion is at a maximum at mid-gestation, followed by a progressive decrease towards term. The high levels at mid-gestation can be interpreted as due simultaneously to a high secretion rate, low peripheral catabolism and absence of feedback mechanism. In contrast, the secretions of PRL (Fig. 1) and TSH are moderate at mid-gestation and only increase in the last trimester of gestation. 2. Effective control by the central nervous system (CNS) of the pituitary secretions is still immature at mid-gestation. The presence in the foetal hypothalamus of releasing factors such as LRF (Fig. 5) and TRF, and of somatostatin (Fig. 6), a growth hormone release inhibiting factor (GIF), has been established. TRF and GIF, but not LRF, are also present in the cerebral cortex. It has been postulated that, early in life, relatively autonomous and unrestrained secretion of hypothalamic hypophysiotropic releasing factors occurs, and that, later in development, there is a maturation of inhibitory or restraining influences mediated via the CNS (feedback mechanisms) that modulates the secretion of the foetal adenohypophyseal hormones (Fig. 3 and 4). 3. Observations made with anencephalic newborn confirm that a functional hypothalamus is necessary during foetal life for the secretion of each of the hormones of the anterior pituitary gland with the exception of PRL, the secretion of which is normal in anencephaly. Although somatostatin probably participates in the regulation of hGH during foetal life, it appears evident from the anencephaly data that this regulation can only be fully understood by postulating the existence of a growth hormone releasing factor (GRF).

Anencephaly↗
PubMedDate not supplied

[Effect of chorionic gonadotropin on thymocyte differentiation in the presence of thymus epithelial cells].

We studied the effects of the main placental hormone, chorionic gonadotropin, on differentiation of human thymocytes in vitro in the presence of thymic epithelial cells. It was shown that the hormone at a high dose (100 IU/ml) enhanced the epithelium-induced phenotypic maturation of thymocytes, which is registered by an increased expression of the membrane marker CD3 and transition of CD4+8+ thymocytes in the cells with CD4+8- and CD4-8+ phenotypes. In addition, gonadotropin enhanced the proliferative response of thymocytes to the mitogen during their cultivation with the epithelium. The stimulating effect of the hormone on the epithelium-induced differentiation of thymocytes is mediated by the humoral factors of epithelial cells. In addition, gonadotropin at this dose exerts its own differentiating activity with respect to thymocytes and stimulates their phenotypic and functional maturation in a monoculture.

Cell Differentiation↗
PubMedDate not supplied

hCG in trophoblast tumour cells of the cell line Jeg3 and hCG isolated from amniotic fluid and serum of pregnant women carry oligosaccharides of the sialyl Lewis X and sialyl Lewis a type.

Human chorionic gonadotropin (hCG) is a placental hormone and marker for the differentiation process of cytotrophoblast cells to syncytial trophoblasts. It is secreted into the maternal circulation and urine. The glycoprotein hCG is also found in the serum and urine of patients with malignant trophoblastic diseases. For this study hCG was purified from pooled human mid-trimester amniotic fluid, serum and urine of pregnant women and from supernatants of trophoblast tumour cell cultures Jeg3 and BeWo by immunoadsorption chromatography with specific hCG-antibodies. The purity and identity of the isolated hCG were checked by Western blot analysis. Sialylated oligosaccharides of the Lewis type of isolated hCGs were analysed by dot blot and ELISA technique with monoclonal antibodies specific for sialyl Lewis x and sialyl Lewis a-carbohydrate epitopes. BeWo and Jeg 3 cells were additionally investigated by immunofluorescence. HCG isolated from the serum and amnion of pregnant women bear both sialyl Lewis x (sLex)-antigen and sialyl Lewis a (sLea)-antigen. The same result was observed for hCG isolated from the supernatants of the trophoblast tumour cell line Jeg3. On the contrary, hCG isolated from the supernatants of the trophoblast tumour cell line BeWo showed only a very weak expression of these antigens. HCG isolated from the urine of pregnant women was negative for both sialyl Lewis antigens. The results are discussed with respect to a possible relationship to selectin- mediated cell adhesion processes. This could play a role in the prevention of leukocyte adhesion on the foetal syncytiotrophoblast. Glycosylation of hCG in trophoblast tumour cells, on the other hand, could increase the metastatic activity of these cells.

Amniotic Fluid↗
PubMedDate not supplied

Stimulation of hCG protein and mRNA levels in trophoblast tumour cells Jeg3 and BeWo by glycodelin A.

The placental hormone human chorionic gonadotropin (hCG) represents a marker for the differentiation process of cytotrophoblast cells into syncytial trophoblasts and is also found in the serum and urine of patients with malignant trophoblastic diseases. During pregnancy, serum concentration curves of hCG and glycodelin A show a similar course. The main source of hCG is the trophoblast and trophoblast cells in vitro show an increased hCG release if treated with glycodelin A. In addition, hCG is a tumour marker for chorion carcinoma cells. We investigated the effect of native and recombinant glycodelin on the trophoblast tumour cells Jeg3 and BeWo and the role of expression plasmids of glycodelin A in the same cells. Our study shows that glycodelin A stimulates the secretion of hCG protein in Jeg3 trophoblast tumour cells in a time- and dose-dependent manner. Our results were confirmed on the mRNA level by real-time RT-PCR. The effect of glycodelin A on hCG mRNA regulation is time- and dose-dependent. We observed an increase of hCG mRNA copy numbers after glycodelin A treatment leading to a higher hCG protein production. Glycodelin A had no effect on BeWo trophoblast tumour cells, suggesting that production of hCG is not regulated by glycodelin A in these cells.

Chorionic Gonadotropin↗
PubMed2004

Excess of amniotic fluid: pathophysiology, correlated diseases and clinical management.

The evaluation of amniotic fluid volume represents, together with the evaluation of fetal growth, one of the most important indicators of fetal wellbeing. Amniotic fluid is produced by fetal urines with small aliquots from fetal membranes and lung fluids. The main determinant of its turnover is fetal swallowing together with a small absorption through fetal skin and membranes. The pathologic conditions that lead to an excess of amniotic fluid are represented by excessive production or by a reduction of the physiologic turnover. The most frequent cause is gestational diabetes. This complication can be diagnosed in 2-3% of pregnancies, as a result of increased insulin resistance, most frequently found in association with risk factors such as high maternal BMI. Placental hormones, such as HPL, act indeed to increase insulin resistance and can therefore lead to post-prandial hyperglycemia in predisposed mothers. Maternal hyperglicemia leads in turn to fetal hyperglycemia and fetal hyperinsulinemia. Increased amniotic fluid volume is not a constant feature, being associated with the most severe cases, but its evaluation is very useful in the clinical management. The resulting increase in uterine volume, also related to accelerated fetal growth, is a potential cause of premature delivery, a severe complication also considering the delay in fetal lung maturation observed with fetal hyperinsulinemia. The evaluation of the degree of polyhydramnios has to be pursued by ultrasound. Precise diagnostic steps must be followed in order to rule out other potentially associated causes. Amongst these, malformations of the intestinal tract, such as hesophageal atresia, that are associated with decreased or absent fetal swallowing, must be considered. The clinical workout must therefore include an ultrasound evaluation of fetal morphology together with an oral glucose tolerance test. The therapeutic approach will be defined according to the definition of the underlying cause. Many cases will benefit from bedrest, tocolysis and induction of lung maturation.

Diabetes, Gestational↗