Mercy A. Nuamah

Cyclic mechanical stretching and interleukin-1α synergistically up-regulate prostacyclin secretion in cultured human uterine myometrial cells

Prostacyclin (PGI2), a potent uterine smooth muscle relaxant, is postulated to be a major prostaglandin (PG) secreted from the human myometrium. PGI2metabolite concentrations in the maternal plasma were reported to be elevated during pregnancy, especially during labor. Recently, we developed cultured human myometrial cells from pregnant women and reported that cyclic mechanical stretching mimicking labor increased PGI2secretion from these cells by up-regulating PGI2synthase promoter activities. Since elevation of cervical/vaginal interleukin-1α (IL-1α) concentrations is also a characteristic feature of delivery, and IL-1α is a known stimulator of PGsynthesis, we investigated a possible synergistic effect of cyclic mechanical stretching and IL-1α on PGI2production in cultured human myometrial cells. Treatment with IL-1α (10 ng/ml) significantly augmented (4- to 60-fold) the secretion of PGI2, prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and thromboxane A2(TXA2) from cultured human myometrial cells obtained from non-pregnant and pregnant women as well as in cultured human umbilical artery and cultured human coronary artery smooth muscle cells (p<0.05 for all comparisons). However, labor-like cyclic mechanical stretching up-regulated IL-1α-augmented PGI2secretion from myometrial cells obtained from nonpregnant and pregnant women 2.1- to 2.8-fold (p<0.05 for all comparisons), but not PGE2, PG F2αnor TXA2. Moreover, such an augumentation of PGI2secretion by cyclic mechanical stretching was not observed in cultured human umbilical artery nor in cultured human coronary artery smooth muscle cells. These results suggest that cyclic mechanical stretching by labor, in concert with IL-1α stimulation, contributes to the increase in myometrial PGI2secretion during delivery.

Leptin as a novel placenta-derived hormone in humans

Summary These studies provide the first evidence for leptin as a novel placenta-derived hormone in humans, and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and in pregnancies complicated with preeclampsia or gestational trophoblastic diseases. To elucidate the role of leptin in human pregnancy, further investigations on the following points are required. o 1. Mechanism of resistance to high plasma leptin levels during pregnancy has not been elucidated. Studies on down-regulation of leptin receptor and changes in the plasma concentrations of leptin binding protein, which is identical to soluble leptin receptor, Ob-Re, may provide an answer to this question. 2. Possible candidates of the biological significance of placenta-derived leptin in pregnancy may be; a) effects on maternal glucose and lipid metabolism, b) regulation of placental function, and c) effects on fetal growth and development. 3. Identification of distribution of leptin receptors in intra-uterine tissues is crucial to understand the role of placenta-derived leptin during pregnancy.