ArticleEndocrinology2020
Salt-inducible Kinases Are Critical Determinants of Female Fertility.
Article in Endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- The Role of the Salt-inducible Kinases in the Endocrine Glands.Endocrinology · 2025Review
- SIK2 and SIK3 Differentially Regulate Mouse Granulosa Cell Response to Exogenous Gonadotropins In Vivo.Endocrinology · 2024Article
- Transcriptome profiling reveals dysregulation of inflammatory and protein synthesis genes in PCOS.Scientific reports · 2024Article
- Salt-inducible kinases regulate androgen synthesis in theca cells by enhancing CREB signaling.Molecular and cellular endocrinology · 2023Article
- Structure-based design of selective, orally available salt-inducible kinase inhibitors that stimulate bone formation in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanism of negative modulation of FSH signaling by salt-inducible kinases in rat granulosa cells.Frontiers in endocrinology · 2022Article
- Oocyte-secreted factors strongly stimulate sFRP4 expression in human cumulus cells.Molecular human reproduction · 2021Article
- Recent advances in understanding gonadotropin signaling.Faculty reviews · 2021Review
- Molecular crosstalk between insulin-like growth factors and follicle-stimulating hormone in the regulation of granulosa cell function.Reproductive medicine and biologyReview
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Follicle development is the most crucial step toward female fertility and is controlled mainly by follicle-stimulating hormone (FSH). In ovarian granulosa cells (GCs), FSH activates protein kinase A by increasing 3',5'-cyclic adenosine 5'-monophosphate (cAMP). Since cAMP signaling is impinged in part by salt-inducible kinases (SIKs), we examined the role of SIKs on the regulation of FSH actions. Here, we report that SIKs are essential for normal ovarian function and female fertility. All SIK isoforms are expressed in human and rodent GCs at different levels (SIK3>SIK2>SIK1). Pharmacological inhibition of SIK activity potentiated the stimulatory effect of FSH on markers of GC differentiation in mouse, rat, and human GCs and estradiol production in rat GCs. In humans, SIK inhibition strongly enhanced FSH actions in GCs of patients with normal or abnormal ovarian function. The knockdown of SIK2, but not SIK1 or SIK3, synergized with FSH on the induction of markers of GC differentiation. SIK inhibition boosted gonadotropin-induced GC differentiation in vivo, while the genomic knockout of SIK2 led to a significant increase in the number of ovulated oocytes. Conversely, SIK3 knockout females were infertile, FSH insensitive, and had abnormal folliculogenesis. These findings reveal novel roles for SIKs in the regulation of GC differentiation and female fertility, and contribute to our understanding of the mechanisms regulated by FSH. Furthermore, these data suggest that specific pharmacological modulation of SIK2 activity could be of benefit to treat ovulatory defects in humans and to increase the propagation of endangered species and farm mammals.
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Registered trials
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.