Activins and activin antagonists in the human ovary and ovarian cancer

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens

“…NE-mediated ADRB2 and CREB signaling in cancer cells is important for increasing angiogenesis, tumor invasion, and inflammation. Inhibin β A is a member of the TGF-β pathway and is overexpressed in prostate, ovarian, colorectal, and breast cancers (31)(32)(33). Elevated serum and plasma levels of inhibin β A have been reported in patients with metastatic ovarian, breast, and prostate cancers (31)(32)(33).…”

“…Inhibin β A is a member of the TGF-β pathway and is overexpressed in prostate, ovarian, colorectal, and breast cancers (31)(32)(33). Elevated serum and plasma levels of inhibin β A have been reported in patients with metastatic ovarian, breast, and prostate cancers (31)(32)(33). Inhibin β A is shown to have other effects on tumors such as promoting stem cell phenotype and modulating cancer cachexia (34).…”

The role of FSH and TGF-β superfamily in follicle atresia

“…Activin was originally discovered in the 1980’s and was named for its activating efficacy in releasing FSH from pituitary gonadotropines [ 97 ]. Activins are homogenous or heterogenous dimers consisting of four already known subunits, βA, βB, βC and βE.…”

CNOT6/6L-mediated mRNA degradation in ovarian granulosa cells is a key mechanism of gonadotropin-triggered follicle development

“…According to canonical theories, FSH performs these functions by stimulating target gene transcription in GCs. The known FSH target genes include Ccnd2, which encodes cyclin D2 and is required for GC proliferation (Han et al, 2013); Cyp19a1, which encodes aromatase, the key enzyme of estrogen biosynthesis (Fan et al, 2009;Kidokoro et al, 2009); Fshr, which encodes the FSH receptor and endows the GC responsiveness to FSH (Stilley and Segaloff, 2018;Wang and Greenwald, 1993); and Inhba and Inhbb, which encode activin, a multifunctional growth and differentiation factor of the transforming growth factor-b (TGF-b) family (Reader and Gold, 2015;Vale et al, 1988). Recent studies have revealed previously unnoticed post-transcriptional regulation of ovarian follicle development by gonadotropin.…”