ArticleMolecular endocrinology (Baltimore, Md.)2010
Human chorionic gonadotropin stimulates theca-interstitial cell proliferation and cell cycle regulatory proteins by a cAMP-dependent activation of AKT/mTORC1 signaling pathway.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population.Scientific reports · 2023Article
- Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease.International journal of molecular sciences · 2023Review
- Hippo Signaling in the Ovary: Emerging Roles in Development, Fertility, and Disease.Endocrine reviews · 2022Review
- Human Chorionic Gonadotropin and Early Embryogenesis: Review.International journal of molecular sciences · 2022Review
- Single-cell RNA-seq analysis and cell-cluster deconvolution of the human preovulatory follicular fluid cells provide insights into the pathophysiology of ovarian hyporesponse.Frontiers in endocrinology · 2022Article
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
- Human Chorionic Gonadotrophin: New Pleiotropic Functions for an "Old" Hormone During Pregnancy.Frontiers in immunology · 2020Review
- Sp1 regulates steroidogenic genes and LHCGR expression in primary human luteinized granulosa cells.The Journal of steroid biochemistry and molecular biology · 2019Article
- Role of mTOR Signaling in Female Reproduction.Frontiers in endocrinology · 2019Review
- Human Chorionic Gonadotropin Influences Systemic Autoimmune Responses.Frontiers in endocrinology · 2018Article
- HCG-mediated activation of mTORC1 signaling plays a crucial role in steroidogenesis in human granulosa lutein cells.Endocrine · 2016Article
- The Role of Foxo3 in Leydig Cells.Yonsei medical journal · 2015Article
- Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling.EXCLI journal · 2015Article
- mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).Human molecular genetics · 2014Article
- CGB activates ERK and AKT kinases in cancer cells via LHCGR-independent mechanism.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Postnatal exposure to chromium through mother's milk accelerates follicular atresia in F1 offspring through increased oxidative stress and depletion of antioxidant enzymes.Free radical biology & medicine · 2013Article
- Stimulatory effect of insulin on theca-interstitial cell proliferation and cell cycle regulatory proteins through MTORC1 dependent pathway.Molecular and cellular endocrinology · 2013Article
- Luteinizing hormone/human chorionic gonadotropin-mediated activation of mTORC1 signaling is required for androgen synthesis by theca-interstitial cells.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Metformin: direct inhibition of rat ovarian theca-interstitial cell proliferation.Fertility and sterility · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In addition to playing a cardinal role in androgen production, LH also regulates growth and proliferation of theca-interstitial (T-I) cells. Here, we show for the first time that LH/human chorionic gonadotropin (hCG) regulates T-I cell proliferation via the mammalian target of rapamycin complex 1 (mTORC1) signaling network. LH/hCG treatment showed a time-dependent stimulation of T-I cell proliferation and phosphorylation of protein kinase B (AKT), ERK1/2, and ribosomal protein (rp)S6 kinase 1 (S6K1), and its downstream effector, rpS6. Pharmacological inhibition of ERK1/2 signaling did not block the hCG-induced phosphorylation of tuberin, the upstream regulator of mTORC1 or S6K1, the downstream target of mTORC1. However, inhibition of AKT signaling completely blocked the hCG response. Furthermore, the AKT-specific inhibitor abolished forskolin (FSK)-stimulated phosphorylation of AKT, tuberin, S6K1, and rpS6. Human CG and FSK-mediated phosphorylation of AKT and downstream targets of mTORC1 were attenuated by inhibition of adenylyl cyclase. Pharmacologic targeting of mTORC1 with rapamycin also abrogated hCG or FSK-induced phosphorylation of S6K1, rpS6, and eukaryotic initiation factor 4E binding protein 1. In addition, hCG or FSK-mediated up-regulation of the cell cycle regulatory proteins cyclin-dependent kinase 4, cyclin D3, and proliferating cell nuclear antigen was blocked by rapamycin. These results were further confirmed by demonstrating that knockdown of mTORC1 using small interfering RNA abolished hCG-mediated increases in cell proliferation and the expression of cyclin D3 and proliferating cell nuclear antigen. Taken together, the present studies show a novel intracellular signaling pathway for T-I cell proliferation involving LH/hCG-mediated activation of the AKT/mTORC1 signaling cascade.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.