The cAMP signalling system and human trophoblast function

Strauss, Jerome F.; Kido, Susumu; Sayegh, Raja; Sakuragi, Noriaki; Gåfvels, Mats

doi:10.1016/0143-4004(92)90047-w

Cited by 108 publications

(50 citation statements)

References 75 publications

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“…In addition, both hCG and cAMP pathway have been demonstrated to promote trophoblast syncytialization (Strauss et al 1992, Shi et al 1993, Yang et al 2003, which may, at least in part, account for the effect of hCG/cAMP on leptin production during syncytialization. However, in this study, the effect of hCG/cAMP on leptin production was studied in the placental trophoblasts 3 days after plating in medium containing 10% NCS.…”

Section: Discussionmentioning

confidence: 99%

“…The role of hCG in the maintenance of pregnancy is well known for stimulating progesterone synthesis, promoting uterine quiescence, regulating implantation, and controlling trophoblastic hormonal secretion and differentiation (Shi et al 1993, Cronier et al 1994, Kraiem et al 1994, Kurtzman et al 2001. It is well established that hCG shares the same receptor with pituitary LH and the hCG/LH receptor is coupled to Gas protein using the cAMP pathway in its signal transduction (Strauss et al 1992). Exogenous hCG is reported to stimulate leptin production in human placental explants and immortalized cell lines (Maymo et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts

Li²,

Ni³

et al. 2011

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Leptin produced by the placental syncytiotrophoblasts participates in a number of processes in pregnancy including implantation, proliferation of the cytotrophoblasts, and nutrient transfer across the placenta. Despite the functional significance of leptin in pregnancy, the regulation of leptin synthesis is poorly understood in human placental syncytiotrophoblasts. In this study, we investigated the role of endogenous human chorionic gonadotropin (hCG) in the regulation of leptin production as well as the underlying mechanism involving the cross talk between cAMP and p38 mitogen-activated protein kinase (MAPK) pathways. We found that neutralization of endogenous hCG with its antibody dose dependently decreased leptin mRNA level and secretion, whereas exogenous hCG increased leptin mRNA level and secretion. Activation of the cAMP pathway with dibutyryl cAMP (db cAMP) or forskolin recapitulated the stimulatory effect of hCG on leptin expression. Inhibition of protein kinase A with H89 not only reduced the basal leptin expression but also attenuated the induced leptin expression by hCG. Treatment of the syncytiotrophoblasts with db cAMP and hCG phosphorylated p38 MAPK. Inhibition of p38 MAPK with SB203580 not only reduced the basal leptin production but also attenuated the leptin-induced production by both hCG and db cAMP. These data suggest that endogenous hCG plays a significant role in maintaining leptin production in human placental syncytiotrophoblasts, and this effect involves a cross talk between cAMP and p38 MAPK pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts

Li²,

Ni³

et al. 2011

Reproduction

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“…37 The binding of cAMP to proteins such as PKA and exchange protein activated by cAMP explains most of its functional activities. Although H89 has nonspecific effects, 38 it is a tool widely used to assess the role of PKA in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP–PKA Signaling Pathway

et al. 2016

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Abstract-The effects of fluid shear stress (FSS) on the human syncytiotrophoblast and its biological functions have never been studied. During pregnancy, the syncytiotrophoblast is the main source of placental growth factor (PlGF), a proangiogenic factor involved in the placental angiogenesis and the vascular adaptation to pregnancy. The role of FSS in regulating PlGF expression in syncytiotrophoblasts is unknown. We investigated the impact of FSS on the production and secretion of the PlGF by the human syncytiotrophoblasts in primary cell culture. Laminar and continuous FSS (1 dyn cm −2) was applied to human syncytiotrophoblasts cultured in a parallel-plate flow chambers. Secreted levels of PlGF, sFlt-1 (soluble fmslike tyrosin kinase-1), and prostaglandin E2 were tested by immunologic assay. PlGF levels of mRNA and intracellular protein were examined by RT-PCR and Western blot, respectively. Intracellular cAMP levels were examined by timeresolved fluorescence resonance energy transfer cAMP accumulation assay. Production of cAMP and PlGF secretion was significantly increased in FSS conditions compared with static conditions. Western blot analysis of cell extracts exposed to FSS showed an increased phosphorylation of protein kinase A substrates and cAMP response element-binding protein on serine 133. FSS-induced phosphorylation of cAMP response element-binding protein and upregulation of PlGF were prevented by inhibition of protein kinase A with H89 (3 μmol/L). FSS also triggers intracellular calcium flux, which increases the synthesis and release of prostaglandin E2. The enhanced intracellular cAMP in FSS conditions was blocked by COX1/COX2 (cyclooxygenase) inhibitors, suggesting that the increase in prostaglandin E2 production could activate the cAMP/protein kinase A pathway in an autocrine/paracrine fashion. FSS activates the cAMP/protein kinase A pathway leading to upregulation of PlGF in human syncytiotrophoblast.

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“…It was demonstrated that in BeWo cells and human-term placental tissue, leptin secretion is augmented by forskolin, an activator of PKA (Yura et al 1998). On the other hand, cAMP is known to alter human trophoblast function as demonstrated in numerous in vitro studies of normal and transformed trophoblast cells (Strauss et al 1992).…”

Section: Signal Transduction Pathways Mediating Leptin Inductionmentioning

confidence: 99%

Involvement of leptin in the molecular physiology of the placenta

Schanton¹,

Maymó²,

Pérez-Pérez³

et al. 2018

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Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli

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The cAMP signalling system and human trophoblast function

Cited by 108 publications

References 75 publications

Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts

Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts

Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP–PKA Signaling Pathway

Involvement of leptin in the molecular physiology of the placenta

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