Effect of epidermal growth factor on inhibin secretion in human placental cell culture.

The effect of epidermal growth factor (EGF) on inhibin secretion was investigated in a primary culture of human placental cells. Dissociated cells were cultured with EGF, FSH, 8-Br-cAMP, and two agents known to increase intracellular cAMP. Inhibin level in the culture medium was measured by immunoenzymatic assay. Addition of EGF (0.1-1000 ng/ml) in the cell culture induced a dose-dependent increase of inhibin levels in the medium after 2 days of culture. Greater response of placental cells to EGF in the inhibin secretion occurred at the doses of 10-1000 ng/ml, where inhibin levels in the medium increased by 84.9-111.5% compared to the control (P < 0.01). FSH stimulated the inhibin secretion in the placental cells. EGF combined with FSH resulted in a greater response of placental cells in inhibin secretion. Addition of FSH (30 ng/ml) and EGF (0.1-1000 ng/ml) in the culture induced inhibin levels significantly higher than that of either FSH alone or EGF alone (P < 0.01). The effect of EGF on inhibin secretion was closely correlated with the seeding density of trophoblasts and the time course of culture. Obvious effect of EGF was found at the number of 1-2 x 10(6) cells per well and after 36-48 h of culture. Addition of 8-Br-cAMP, cholera toxin, or forskolin in the culture increased the inhibin levels more than 6-fold, 5-fold, and 2-fold, compared to the controls, respectively. When EGF combined with one of these agents was added in the culture, the inhibin in the medium increased to a level higher than those with the individual agents alone. EGF resulted in an increase in basal and cAMP induced human CG secretions in the trophoblasts in a similar manner as in the inhibin secretion. However, the effect of EGF on the proliferation of trophoblasts was not observed by measurements of the cell growth with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and DNA content in the cells with fluorescence spectrophotometry. Morphological study showed that EGF induced trophoblasts to differentiate and form syncytium. These data suggest that EGF stimulates inhibin secretion in human placental cells in vitro. EGF and its interaction with other hormones or growth factors may play an important role in the complicated hormonal regulation during human pregnancy.

Circulating bioactive inhibin levels during human pregnancy.

In this study bioactive inhibin was measured in 112 serum samples from 103 pregnant women by a sensitive ovine pituitary cell culture system. Human inhibin activities were detected in a range between 0.02-5.28 U/mL at six dilutions by using serum from the 38-week pregnant women as a quality control. A remarkable increase in serum inhibin was observed from 4 to 38 weeks of pregnancy. The mean serum inhibin level was 1.58 U/mL at 4 weeks. Thereafter, inhibin levels increased progressively with the weeks of pregnancy (r = 0.988; P less than 0.001). In the midterm of pregnancy, serum inhibin was elevated at average levels of 2.84 and 3.84 U/mL at 20 and 28 weeks, respectively. The peak level of inhibin (5.33 U/mL) was obtained at 38 weeks, which was an increase of 237% compared to that at 4 weeks. The average rate of increase in serum inhibin levels was 14.51% every 2-4 weeks (ranging from 8.1-20%). These findings suggest that circulating inhibin is useful marker during human pregnancy.

[Developmental outcome of 5-year-old children born to opiate-dependent mothers: effects of a multidisciplinary intervention during pregnancy]. / Devenir à 5 ans des enfants de mères dépendantes aux opiacés : effets d'un suivi multidisciplinaire pendant la grossesse.

BACKGROUND: Studies on infant outcomes of opiate-dependent pregnant women find a high rate of premature mother-child separation and to a lesser extent developmental delay. The specific role of in utero heroin exposure in the determination of the developmental outcome seems to be less important than the home environment. OBJECTIVE: Describe the health and development of 5-year-old children whose drug-addict mothers allowed an early multidisciplinary intervention (medical and psychological) in the maternity hospital and neonatology. PATIENTS AND METHODS: Thirty-seven children (62% of the initial cohort) were seen in consultation with their parents. Growth and development was compared with a control group of 374 children of the same age. Comparisons were made between the children's and parents' state (social, medical, drug addiction, etc.) upon discharge from the maternity hospital and 5 years later. A study was conducted on those lost to follow-up. RESULTS: The rate of placement in 5 years was very low (13%). Seven children showed a developmental delay, 21 no disorder, and nine some problems. Anxiety (37%) and overweight (48%) were the only disorders differentiating them from the control group. Compliance with the care provided in the maternity hospital was the only item significantly related to the development of the 5-year-old children (P=0.05). DISCUSSION: The hypothesis of an attachment disorder in those with the greatest need is raised. The likely relations between the quality of the care in the maternity hospital, mother-child relations, and the attrition of the cohort are also discussed. CONCLUSION: Management of the symptoms as well as social and psychological care during pregnancy and neonatal hospitalization for opiate-dependent pregnant women facilitates a long-lasting relation with childhood professionals, avoids court-ordered placements, and reduces the appearance of developmental disorders in these children.