Salt Inducible Kinases Are Critical Determinants of Female Fertility.

Salt Inducible Kinases Are Critical Determinants of Female Fertility. Endocrinology. 2020 Apr 28;: Authors: Armouti M, Winston N, Hatano O, Hobeika E, Hirshfeld-Cytron J, Liebermann J, Takemori H, Stocco C Abstract Follicle development is the most crucial step towards female fertility and is controlled mainly by follicle-stimulating hormone (FSH). In ovarian granulosa cells (GCs), FSH activates protein kinase A by increasing cyclic AMP. 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...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research