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Uterine and peripheral blood concentrations of human chorionic gonadotropin and human placental lactogen.

One hypothesis is that two placental protein hormones (human placental lactogen and human chorionic gonadotropin) are effective immunosuppressive agents that prevents the rejection of a fetus because of their very high concentrations. In patients undergoing elective repeat cesarean sections at term, we measured the concentrations of these hormones in blood obtained simultaneously from draining ovarian veins and peripheral veins, and found no significant differences.

Cesarean Section↗

Serum levels of a placental protein during gestation in the baboon.

A placental specific protein (Sp-1) isolated from human placentas was used to establish a radioimmunoassay for measurement of a baboon protein in the sera of pregnant baboons. No reaction was observed with any known pituitary or placental hormone in this assay system. Levels of Sp-1 were detected at 17 to 18 days of gestation and reached high levels by the end of the first trimester of pregnancy. A slow increase in serum levels continued thereafter until parturition. Disappearance of Sp-1 post partum was very slow and required 26 to 34 days to become undetectable in the serum. No function or role of Sp-1 in pregnancy has been suggested, but possible use of its measurement for detecting abnormal placental function deserves investigation.

Animals↗

Serum acetone and liver acetone monooxygenase activity in pregnant rats, fetuses, and neonates: reversible pretranslational reduction of cytochrome P450IIE1 (P450IIE1) during pregnancy.

Serum acetone in neonates was found to increase from < 20 microM at 20 days gestation to 377 +/- 107 microM 1 day after birth. This increase in acetone occurs concurrently with the initial expression of liver P450IIE1 in rat (Song et al., 1986, J. Biol. Chem. 261:16689-16697). Treating pregnant rats with drinking water containing 1% acetone did not result in a premature induction of liver acetone monooxygenase, a P450IIE1 catalyzed activity, in fetuses sacrificed at 20 days gestation. The data indicate that increased serum acetone levels are not responsible for the initial induction of P450IIE1 in neonates. However, acetone monooxygenase activity in their mothers was significantly less than acetone-treated females which were not pregnant, indicating a reduced activity of P450IIE1 during pregnancy although its induction by acetone was still observed. Acetone monooxygenase activity in 20 day pregnant rats given untreated drinking water was also less than in nongravid rats. These findings are supported by immunoblot data which show significant and progressive reductions in liver P450IIE1 in both untreated and acetone-treated rats during pregnancy. Northern mRNA blot analysis further revealed that the decreases in P450IIE1 activity and protein content were mainly due to pretranslational suppression with reduced level of its mRNA. However, their levels rapidly returned to the control level after parturition (within 1 day). Repeated administration of several exogenous hormones (estriol, pregnanediol, thyroxine) or peptide hormones (placental lactogen, prolactin, chorionic gonadotropin) failed to suppress P450IIE1 in nonpregnant rats, indicating a possibility of another factor(s) responsible for the P450IIE1 suppression during pregnancy.

Acetone↗

Human chorionic somatomammotropin gene expression in primary placental cell cultures.

Mono-nucleated cytotrophoblasts (cytoTBs) were prepared by Percoll gradient fractionation of enzymically disaggregated human placental tissue. These cells were plated in monolayer culture in the presence of fetal calf and calf serum. Within 2-24 h, the cytoTBs aggregate, and by 48 h, they are clearly fused into multinucleated syncytia. The presence of human chorionic somatomammotropin (hCS) and chorionic gonadotropin (hCG) in the cells after 48 h was determined by immunohistochemistry. To assess whether hCS is synthesized in our cultures we examined hCS mRNA accumulation with time. The presence of hCS mRNA was detected at the time of plating but full length transcripts were seen only at later times indicating synthesis in culture. However, preparations at the time of plating contain fragments of syncytiotrophoblast (syncytioTB) generated by enzymic or mechanical disaggregation. These fragments could fuse with the cytoTBs. The inclusion of these fragments makes analysis of placental hormones by protein detection an unreliable assay for synthesis. Analysis of mRNA levels support hCS synthesis in culture and correlates with aggregation and fusion of cytoTBs. Thus, the fused cells in culture mimic the cellular site of hCS synthesis in vivo, the syncytioTB.

Cells, Cultured↗

Identification of proliferin mRNA and protein in mouse placenta.

Proliferin is a recently described, prolactin-related protein whose mRNA appears in several murine cell lines during active growth. We have surveyed a number of mouse organs or tissues for the presence of mRNAs that hybridize to cloned proliferin cDNA. Of the tissues tested, only the placenta yielded proliferin-related mRNA. This placental RNA is about 1 kilobase in length, increases sharply between days 8 and 10 of pregnancy, and then gradually declines through day 18. It is more abundant in RNA extracted from the fetal, compared to the maternal, part of the placenta. From a cDNA plasmid library prepared from poly(A)+ placental RNA, two types of proliferin-related clones were isolated, differing in intensity of hybridization to proliferin cDNA. By nucleotide sequence analysis, a strongly hybridizing clone was found to be nearly identical to the proliferin cDNA clone isolated from a library prepared from mRNA of a growing mouse fibroblastic cell line. Using an antiserum prepared against a synthetic proliferin fusion protein, we show that proliferin is secreted as a glycoprotein by minced placental tissue and that it differs from mouse placental lactogen. We conclude that proliferin is a placental hormone that is synthesized in certain mouse cell lines during active growth. Its function during pregnancy and during the growth of cultured cells is presently unknown.

Amino Acid Sequence↗

Hormonally induced differentiation: a novel approach to breast cancer prevention.

Breast cancer, one of the most common neoplasms in women, develops more frequently in those who are nulliparous or late parous, who experience early menarche and late menopause and have a family history of breast cancer. Early parity, late menarche, early menopause, and hormone deprivation exert a protective effect. The mechanisms modulating these variations in malignancy susceptibility are not known. Epidemiologic and experimental studies indicate that malignancies develop in the mammary gland as a result of exposure to carcinogenic stimuli (i.e., chemical carcinogens, radiation). Neoplastic transformation requires that the gland be under specific developmental and age-related conditions at the time of exposure to such agents. In the rat, maximal susceptibility to neoplastic transformation is exhibited by the highly proliferating and undifferentiated gland of the young, virgin, intact females, whereas the fully differentiated gland of parous rats and virgin rats treated with the placental hormone human chorionic gonadotropin is protected from tumor development. Hormonally induced differentiation of the mammary gland is a novel approach to breast cancer prevention and therapy. The development of clinical protocols capitalizing on the protective effect of hormonal treatments mimicking pregnancy in humans is required to validate observations in experimental animal models, and to determine how they relate to epidemiologic and clinical findings. The feasibility of this approach is supported by the observed parallelism between humans and experimental models in both the site of cancer origin and the changes in breast development occurring with parity. Breast cancer initiates in terminal ductal lobular units or lobules type 1, the most undifferentiated structures frequently found in the breast of young nulliparous women.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of the human chorionic gonadotropin alpha- and beta-subunit promoters by AP-2.

Production of the placental hormone, chorionic gonadotropin (CG), increases dramatically as cytotrophoblasts fuse to form syncytiotrophoblasts. The CG alpha- and beta-promoters are both responsive to cAMP, although the kinetics of cAMP stimulation are different. In an effort to understand the mechanisms of coordinate induction of these genes, AP-2 binding sites were identified in the promoter regions of the alpha and CGbeta genes. AP-2 bound to the upstream regulatory element (-186 to -156 base pairs (bp)) in the alpha-promoter and to several different regions of the CGbeta promoter, including footprints 2 and 4B (FP2, -311 to -279 bp; FP4B, 221 to -200 bp). AP-2 antibodies induced supershifts of these complexes, confirming the identity of the protein-DNA complex. In JEG-3 cells, which contain abundant AP-2, mutations in these CGbeta AP-2 sites reduced basal activity and decreased cAMP stimulation. In AP-2-deficient Hep-G2 cells, co-transfection of AP-2 stimulated expression of the CGbeta promoter 10-20-fold, and the alpha-promoter was induced by 3-6-fold. Mutations that eliminate AP-2 binding to CGbeta FP4B reduced AP-2 stimulation by more than 80%, whereas mutations in FP2 reduced AP-2 stimulation by less than 50%. Analyses of AP-2 mutants revealed a requirement for the DNA binding/dimerization domain and the amino-terminal proline-rich and acid-rich transactivation domains for stimulation of the CGbeta promoter. Primary cultures of placental cytotrophoblasts were differentiated into syncytiotrophoblasts in vitro to examine AP-2 expression by reverse transcriptase-polymerase chain reaction. AP-2 mRNA levels increased by day 2 and continued to rise in parallel with a marked increase in alpha and CGbeta gene expression. We conclude that both the alpha and CGbeta promoters contain binding sites for AP-2 and suggest that this transcription factor provides a mechanism for coordinating the induction of these genes during placental cell differentiation.

Cell Nucleus↗

Isolated defect in human placental lactogen synthesis in a normal pregnancy. Case report.

A deficiency in the synthesis of human placental lactogen (hPL) was found in a woman in her second pregnancy. Other placental hormone levels were normal. The woman gave birth to a healthy female infant. hPL deficiency is rare and a survey of the literature has revealed only one previous case report which described the birth of a male infant. The present report of a hPL deficiency is the first associated with the birth of a normal female infant.

Adult↗

[Physiological significance of IGF-I and its binding proteins on fetal growth and maturation].

Insulin-like growth factor-I (IGF-I) is one of growth factors that circulates bound to specific, high affinity binding proteins (IGFBPs). Physiological significance of IGF-I and IGFBPs on fetal growth is investigated in this study. In mother, circulating levels of IGF-I are increased during pregnancy in which placental hormones take the place of pituitary GH to regulate IGF-I during pregnancy and correlates with fetal birth weight. IGFBPs except IGFBP-1 in the maternal circulation are markedly reduced compared to those of non pregnant women due to increased activity of protease(s) while IGFBP-1 gradually increased throughout pregnancy and negatively correlates with fetal weight. IGF-I stimulated 3H-AIB uptake and release by cultured trophoblast cells in a dose dependent manner. Furthermore, fetal growth and the transfer of 3H-AIB to fetus is inhibited when IGF-I is neutralized by polyclonal antibody. These results indicate that maternal IGF-I stimulates fetal growth by activating placental transport of nutrients to fetus. In contrast, IGFBP-1 inhibits both 125I-IGF-I binding to placental membrane and 3H-glycine uptake of trophoblast cells by IGF-I in a dose dependent manner. Moreover, fetal growth and the transfer of 3H-AIB to fetus are accelerated when IGFBP-1 is neutralized by polyclonal antibody, suggesting that maternal IGFBP-1 inhibits fetal growth by inhibiting IGF-I action on the placenta. IGF-I and four IGFBPs including IGFBP-1, -2, -3, and -4 are localized in cytotrophoblast of term placenta. Similarly IGFBP-1, -2, and -4 are detected in medium conditioned by term decidua cells by Western ligand blot in which release of IGFBP-1 and -4 are diminished by IGF-I and all three IGFBPs are increased by progesterone. Thus, there is a complicated autocrine/paracrine regulation between decidua and placenta and IGF-I action on fetal growth is presumed to be modified by this local regulation. Fetal levels of IGF-I and IGFBP-1 are positively and negatively correlate with fetal weight, respectively. The isomers of phosphorylated IGFBP-1 in cord sera are separated by anion ion exchange chromatography in which one nonphosphorylated and four phosphorylated IGFBP-1 are detected. In pared blood samples from mid-term delivery, percentage of nonphosphorylated IGFBP-1 is higher in fetal blood compared to those in mother. Similarly, percentage of nonphosphorylated IGFBP-1 is elevated in AFD infants than is SFD infants from term delivery. Thus, the proportion of nonphosphorylated and phosphorylated isomers of IGFBP-1 varies corresponding to fetal growth.(ABSTRACT TRUNCATED AT 400 WORDS)

Carrier Proteins↗

Studies on chorionic gonadotrophin hormone in rhesus monkeys--disappearance rates.

The disappearance rate of macaque chorionic gonadotrophin (MCG) was investigated in six pregnant monkeys. The animals were hysterectomized with a rapid initial ligature of the uterine and ovarian vessels with minimal uterine manipulation. The entire procedure lasted less than 2 min. Blood samples were drawn before and after the hysterectomy (5, 20, 30, 45, 60, 90, 120 min), and MCG was measured in serum by radioimmunoassay. For all animals, a progressive decrease (rate of disappearance) of MCG values in serum was found, which appeared to follow a double exponential curve. Averaged curves produced disappearance rates of T1/2(1) = 17.2 h for the first compartment (72 h), and T1/2(2) = 87.1 h for the second compartment (156 h). The results suggest that the disappearance of MCG after interruption of pregnancy in rhesus monkey is very similar to that occurring in humans. These data demonstrate that the rhesus monkey is an excellent animal model to study the dynamics of placental hormone secretion in humans.

Abortion, Induced↗

[Serum leptin in women during the third trimester of pregnancy].

Leptin is a small protein produced mainly by adipocytes. Recently, its relationship to obesity has been studied extensively. It was proved that obese individuals have either relative or absolute leptin deficiency. Several years ago, leptin was found to be produced also by the placenta. This stimulated us to study relationship between leptinemia and placental hormones in 85 women in the second gravidity trimester. Within the prenatal screening, these pregnant women were subjected to analysis of AFP, hCG, SP-1 glycoprotein and leptin and the results obtained were processed statistically. The control group consisted of 20 nonpregnant women with tetany. Women in the second gravidity trimester were found to have a significantly higher leptinemia than nongravid women (even with respect to body weight). This may be due to a larger amount of adipose tissue during gravidity and also leptin-resistance. Moreover, we recorded a negative correlation between leptinemia related to body weight and concentration of SP-1 glycoprotein. This finding supports the presumption that mother's leptinemia correlated negatively in the second gravidity trimester with quality and quantity of the placental syncytiotrophoblast. Our findings can be explained as follows: the biological effect of leptin is metabolically unfavourable for the growth of the foetus and the placenta. An increased leptinemia with advancing gravidity can be caused by a larger fatty mass and an increased activity of adipocytes when leptin presence increases in system circulation but the organism begins to be leptin-resistant and an "unfavourable" metabolic effect fort the gravid woman and the foetus is not distinct. These findings thus support the hypothesis postulating the nonsignificance of leptin production in human placenta and on the contrary the necessity of leptin-resistance for foetus development from the metabolic point of view. Thus, a decreased leptinemia immediately before and after the delivery could be caused by the still unclear regulators of leptin sensitivity. This is again a metabolically highly favourable state (reduced appetite, decreased body weight, increased energy output and others).

Adipose Tissue↗

Thyroid hormone efflux from placental tissue is not stimulated during cell volume regulation.

The effects of cell swelling induced by hyposmotic shock on efflux of hybrid hormones and selected amino acids from human placental tissue were examined. Decreasing the osmolarity of external medium from 290 to 140 mOsm/kg stimulated release of taurine, tryptophan and glutamine from placental tissue fragments. The efflux rate constant for taurine increased from 0.0069 +/- 0.0012/min to 0.0646 +/- 0.0217/min (n = 6) (P < 0.001), for tryptophan from 0.016 +/- 0.0010/min to 0.0295 +/- 0.0016/min (n = 6) (P < 0.001), and for glutamine from 0.0267 +/- 0.0027/min to 0.0659 +/- 0.0043/min (n = 4) (P < 0.001). In contrast, hyposmotic challenge did not affect release of triiodothyronine, thyroxine and leucine. These results indicate that transport processes involved in the regulation of cellular volume are unlikely to facilitate efflux of thyroid hormones from placental tissue, and therefore are unlikely to mediate transfer of thyroid hormones across the placenta. In addition, it is unlikely that the transport system facilitating the release of amino acids from placental tissue during regulatory volume decrease is one of the known amino acid carriers.

Cell Size↗

Interleukin-1beta regulation of gonadotropin-releasing hormone messenger ribonucleic acid in cultured human endometrial stromal cells.

OBJECTIVE: To investigate the role of interleukin-1beta (IL-1beta) in regulating GnRH mRNA expression in cultured human endometrial stromal cells using a modified semiquantitative competitive reverse transcription and polymerase chain reaction (PCR). DESIGN: A controlled study. SETTING: Clinical and academic research setting in a university medical center. PATIENT(S): Women undergoing hysterectomy for nonmalignant indications. INTERVENTION(S): Confluent stromal cell cultures treated with steroid hormones were stimulated with IL-1beta and attenuated by anti-IL-1beta antibody or IL-1 receptor antagonist. MAIN OUTCOME MEASURE(S): The human endometrial stromal cell expression of GnRH and its receptor were determined by PCR. Interleukin-1beta-mediated regulation of stromal cell GnRH mRNA expression was determined by quantitative competitive PCR. RESULT(S): The GnRH and GnRH receptor mRNA expression were amplified in cultured stromal cells by PCR and two rounds of nested PCR, respectively. Treatment with IL-1beta stimulated stromal cell GnRH mRNA expression at concentrations of IL-1beta above 10 IU/mL. Recombinant IL-1 receptor antagonist and anti-IL-1beta antibody attenuated the increase of gene expression of GnRH initiated by IL-1beta. CONCLUSION(S): These results provide indirect evidence that IL-1beta may play a crucial role at the level of embryo-maternal interaction by regulating stromal cell expression of GnRH and its receptor, both known to be important in mediating trophoblast invasion and placental hormone regulation.

Base Sequence↗

Cellular localization of chorionic gonadotropin in human fetal kidney and liver.

Earlier, we reported that second trimester human fetal kidney and, to a much lesser extent, human fetal liver were capable of synthesizing and secreting the beta-subunit of hCG. Recently, we also have shown that these tissues, likewise, synthesize and secrete the alpha-subunit of hCG. The hCG produced is biologically active. To determine the cellular localization of these peptides, immunocytochemical studies were performed on human fetal tissues using antibodies against beta hCG, alpha hCG, and the intact hormone. Placental syncytiotrophoblast served as an immunopositive control. In the human fetal kidney, the ascending (thick) limb of the loop of Henle, distal convoluted tubule, and occasional cells in the collecting ducts were distinctly immunopositive for both beta hCG and the alpha-subunit. Small amounts of light positive staining occurred in only a few hepatocytes. Placental syncytiotrophoblast was routinely positive for both subunits, but fetal lung and striated muscle were negative. These immunocytochemical results indicate that immunoreactive beta hCG as well as the alpha-subunit are present in placental syncytiotrophoblast, in the distal renal nephron, and in a limited population of hepatocytes. The qualitative number and intensity of immunopositive cells closely correlate with the quantitative amounts of their hCG subunit synthesis. Taken together with our previous biosynthetic data, the immunocytochemical localization reported here indicates the probable cellular sites of alpha- and beta hCG synthesis in these tissues. The presence of comparable alpha- and beta-subunit staining in identical cell populations suggests that both hCG subunits and, therefore, perhaps intact hCG are produced at these same cellular sites during fetal life.

Chorionic Gonadotropin↗

Trophoblastic cells of the hydatidiform mole contain a beta 1-subtype adrenergic receptor.

Both beta 1- and beta 2-adrenergic receptors have been previously described in normal human placental homogenates; the cells upon whose surface membranes these receptors reside have not been identified. In order to show that a beta 1-adrenergic receptor is present on trophoblastic cells, the cells which mediate maternal-fetal transport and produce placental hormones, beta-adrenergic receptors were demonstrated in membrane fractions of human hydatidiform mole. Microscopic sections of the mole samples used demonstrated edematous villi lined by trophoblastic cells with minimal nontrophoblastic (stromal or vascular) contamination compared with placenta. (--)-[3H]Dihydroalprenolol [(--)-[3H]DHA] binding to molar membranes was reversible and saturable to a single class of sites (Kd = 0.97 +/- 0.12 nM; n = 7; maximum binding capacity, 72.9 +/- 6.4 fmol/mg protein). (--)-[3H]DHA binding was associated with catecholamine-stimulated adenylate cyclase activity. Agonist competition for the molar beta-adrenergic receptor showed the order of potency to be (--)isoproterenol much greater than norepinephrine = epinephrine, characteristic of a beta 1-adrenergic receptor subtype. Competition for (--)-[3H]DHA binding to trophoblastic membranes by the beta-adrenergic receptor subtype-specific agents metoprolol (beta 1 selective) and zinterol (beta 2 selective) was also characteristic of a homogeneous subtype of beta 1-adrenergic receptors. Because beta 1-adrenergic receptors alone were seen on trophoblast cells, the beta 2-adrenergic receptor in placenta must reside on nontrophoblastic elements (stromal or vascular endothelium). No differences in beta-adrenergic receptor binding were seen related with ploidy (2 or 3 N), the presence or absence of a fetus, or the progression of the mole to choriocarcinoma. Two choriocarcinoma cell lines, BeWo and JEG-3, however, showed no specific (--)-[3H]DHA binding. Human trophoblast contains beta 1-adrenergic receptors coupled to catecholamine-sensitive adenylate cyclase, supporting a role for catecholamines in the regulation of placental metabolism.

Adenylyl Cyclases↗

Maternal and fetal hypothalamo-pituitary-adrenal axis: different response depends upon the mode of parturition.

OBJECTIVES: The changes in corticotropin releasing hormone (CRH), adrenocorticotropin hormone (ACTH), cortisol and dehydroepiandrosterone (DHEA) in maternal and fetal plasma were estimated in two group of women undergoing labour after oxytocin induction, or elective cesarean section to correlate changes in maternal and fetal HPA axis to the different stressor conditions. MATERIALS AND METHODS: Blood was sampled from a maternal peripheral vein two days before labour, during the second stage of labour and on the second postnatal day, and also from umbilical vessels just after delivery. Hormone concentrations were measured by RIA and ELSA methods. The maternal plasma CRH concentration before and after labour was similar in both studied groups. RESULTS: Plasma CRH levels measured before labour in both groups were similar, but during labour after oxytocin infusion declined, and was in group of women with elective cesarean section rose, after the delivery there was no difference between groups. The plasma ACTH prior to the delivery was at the same level in all subjects, during the third stage of labour ACTH rose in the both groups, but was statistically higher in group with oxytocin infusion. The concentrations of cortisol before delivery was similar in both groups, then rose to the same level during the delivery and then declined to the level observed before delivery. The DHEA concentration was similar in both groups, did not change during the labour, there was no difference between its level in the umbilical vein and artery. In the group with oxytocin-induction there was no correlation between maternal CRH and ACTH or cortisol concentration, but such a correlation occurred in the group with elective cesarean section. The concentration of ACTH and DHEA in umbilical artery was similar in both groups but the concentrations of CRH and cortisol in umbilical artery in group of newborns delivered after elective cesarean section were statistically higher. CONCLUSION: The activity of the mother's HPA axis is partially inhibited rather by psychological stressors, than events connected with mode of parturition. The newborn's HPA axis responds in a specific way to mother's HPA-axis. The communication between mother's and newborn's HPA is possibly related to many other factors than placental CRH and ACTH. It is necessary to consider effects of central CRH and ACTH on the fine-tune regulation of HPA axis in the late pregnancy and parturition, not detectable due to the high levels of placental hormones.

Adrenocorticotropic Hormone↗

Binding of human growth hormone (GH)-variant (placental GH) to GH-binding proteins in human plasma.

Human GH-variant (hGH-V) is a natural GH analog arising from the hGH-V gene. It is expressed in the placenta and secreted into the maternal circulation during the second half of pregnancy. To gain information about its bioactivity in man, we examined the interaction of hGH-V with the high affinity GH-binding protein/receptor (GH-BP) in human plasma. hGH-V was equipotent with pituitary hGH (hGH-N) as a ligand for the GH-BP. hGH-N/hGH-V chimeric proteins, where the sequences encoded by exon 3 (amino acid residues 32-71, thought to be exposed on the molecule's surface and involved in receptor binding) were exchanged, also bound with similarly high affinities. A corresponding hGH-N/rat PRL chimeric protein had 25-fold reduced affinity for the GH-BP. We conclude that hGH-V is a potent somatogen in man, and that some of the manifestations of late pregnancy, such as increased insulin-like growth factor-I levels and coarsening of features, are probably related to the high circulating levels of hGH-V. GH-BP measurements in pregnancy must take into account BP saturation by endogenous hGH-V.

Binding, Competitive↗

Changes of dimeric inhibin B levels in maternal serum throughout healthy gestation and in women with gestational diseases.

Human placenta expresses subunit messenger RNAs for synthesizing inhibin A and B. Experimental studies have shown an effect of inhibins on placental hormone secretion, but an endocrine function is suggested by the high levels in maternal circulation. Although information is available on the changes of inhibin A in serum of healthy pregnant women, data on inhibin B levels are limited to early gestation. The aim of the present study was to investigate the changes of inhibin B levels in maternal circulation in healthy pregnant women throughout gestation, and to evaluate whether early pregnancy disturbances or gestational diseases are characterized by abnormal inhibin B levels. The protocol included various groups of pregnant women. A longitudinal evaluation of serum inhibin B levels was done at specific intervals (8-12, 13-18, 19-24, 25-28, 29-33, and 34-40 weeks) in the following groups: 1) healthy pregnant women (n = 13); 2) women at risk of hypertension who did not develop hypertension (n = 8); and 3) women with chronic hypertension (n = 13). In women in group 1, a blood sample was also obtained in the postpartum period (12, 24, and 48 h after delivery). Other pregnant women with abnormal bleeding in the first trimester were studied; they were subdivided into women with ongoing pregnancy (n = 12); and women with miscarriage (n = 22); a control group of healthy pregnant women at the same gestational age was also included (n = 18). A final group of women with gestational diseases (n = 34) was included in the study and included women with: 1) pregnancy-induced hypertension (n = 10); 2) preeclampsia (n = 17); and 3) intrauterine fetal growth retardation (n = 7). A group of healthy nonpregnant women (n = 9) was used as controls, and a blood specimen was collected during both the early- to midfollicular and midluteal phases of the menstrual cycle. Serum dimeric inhibin B levels were measured by using a double-antibody enzyme-linked immunoadsorbent assay. Early gestation inhibin B levels were similar to those of nonpregnant controls and showed a significant rise during the third trimester (P < 0.01). The highest maternal serum inhibin B levels were found at term (P < 0.01). Values significantly returned to control levels within 12-48 h (P < 0.01) after placental delivery. Women at risk of hypertension showed a similar gestational-related increase of inhibin B levels during the third trimester, without any significant difference when compared with healthy women. Women with chronic hypertension showed significantly lower levels at term (P < 0.01). Women with pregnancy-induced hypertension or preeclampsia, or who were carrying a fetus with intrauterine growth retardation showed serum inhibin B levels during the third trimester of gestation consistently lower than in control healthy women at the same gestational age (P < 0.001, mean +/- SEM). Maternal serum inhibin B levels in women with early pregnancy bleeding or miscarriage were similar to those of healthy pregnant women at the same gestational age, independent from the outcome of gestation. The present study showed that maternal serum inhibin B levels increase in the last trimester of normal pregnancy, with low levels in women with hypertensive disturbances or intrauterine growth retardation.

Adult↗