ArticleCell communication and signaling : CCS2022
HB-EGF upregulates StAR expression and stimulates progesterone production through ERK1/2 signaling in human granulosa-lutein cells.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 15 citations in OpenAlex.
- The roles of MAPK signaling pathway in ovarian folliculogenesis.Journal of ovarian research · 2025Review
- Landscape transcriptomic analysis of bovine follicular cells during key phases of ovarian follicular development.Biological research · 2024Article
- The Multiple Functions of HB-EGF in Female Reproduction and Related Cancer: Molecular Mechanisms and Targeting Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Resveratrol Protects Rat Ovarian Luteinized Granulosa Cells from HInternational journal of molecular sciences · 2023Article
- Resveratrol stimulates StAR expression and progesterone production by GPER-mediated downregulation of Snail expression in human granulosa cells.Journal of food and drug analysis · 2023Article
- Signaling pathways and targeted therapeutic strategies for polycystic ovary syndrome.Frontiers in endocrinology · 2023Review
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9 authors at 1 institution in 1 country.
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Abstract
backgroundHeparin-binding epidermal growth factor-like growth factor (HB-EGF) belongs to the epidermal growth factor (EGF) family of growth factors. HB-EGF and its receptors, epidermal growth factor receptor (EGFR) and HER4, are expressed in the human corpus luteum. HB-EGF has been shown to regulate luteal function by preventing cell apoptosis. Steroidogenesis is the primary function of the human corpus luteum. Steroidogenic acute regulatory protein (StAR) plays a critical role in steroidogenesis. StAR expression and progesterone (P4) production in human granulosa-lutein (hGL) cells have been shown to be upregulated by a ligand of EGFR, amphiregulin. However, whether HB-EGF can achieve the same effects remains unknown.
methodsA steroidogenic human ovarian granulosa-like tumor cell line, KGN, and primary culture of hGL cells obtained from patients undergoing in vitro fertilization treatment were used as experimental models. The underlying molecular mechanisms mediating the effects of HB-EGF on StAR expression and P4 production were explored by a series of in vitro experiments.
resultsWestern blot showed that EGFR, HER2, and HER4 were expressed in both KGN and hGL cells. Treatment with HB-EGF for 24 h induced StAR expression but did not affect the expression of steroidogenesis-related enzymes, P450 side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase, and aromatase. Using pharmacological inhibitors and a siRNA-mediated knockdown approach, we showed that EGFR, HER4, but not HER2, were required for HB-EGF-stimulated StAR expression and P4 production. In addition, HB-EGF-induced upregulations of StAR expression and P4 production were mediated by the activation of the ERK1/2 signaling pathway.
conclusionThis study increases the understanding of the physiological role of HB-EGF in human luteal functions. Video Abstract.
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