Follicle‐stimulating hormone promotes age‐related endometrial atrophy through cross‐talk with transforming growth factor beta signal transduction pathway

Abstract

It is widely believed that endometrial atrophy in postmenopausal women is due to an age-related reduction in estrogen level. But the role of high circulating follicle-stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post-OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin-releasing hormone agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted the apoptosis of primary cultured endometrial cells in a dose-dependent manner. In addition, upregulation of caspase3, caspase8, caspase9, autophagy-related proteins (ATG3, ATG5, ATG7, ATG12 and LC3) and downregulation of c-Jun were also observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time-dependent activation in endometrial cells which can be partly inhibited by blocking the transforming growth factor beta receptor II (TβRII). In conclusion, FSH regulated endometrial atrophy by affecting the proliferation, autophagy and apoptosis of endometrial cells partly through activation of the transforming growth factor beta (TGFβ) pathway.

Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1α in mouse granulosa cells

“… 44 Inhibition of TGF β signaling by blocking TGF β R2 significantly decreased FSH-mediated autophagy signaling. 45 In porcine GCs, FSH increased the level of inhibitor of NF- κ B (I κ B) protein and subsequently increased autophagy via JNK signaling. 46 In this study, we demonstrated that FSH administration enhanced autophagy in MGCs.…”

Fructus Ligustri Lucidi modulates estrogen receptor expression with no uterotrophic effect in ovariectomized rats

“…Inhibition of FSH also impairs bone loss and further prevents LH release while the alteration does not play a dominant role in the development of osteoporosis [ 35 ]. In addition, high circulating FSH contributes to endometrial atrophy in mice [ 36 ]. Increased circulating LH may be associated with postmenopausal “hot flushes” [ 37 ].…”

Hypoglycosylated hFSH Has Greater Bioactivity Than Fully Glycosylated Recombinant hFSH in Human Granulosa Cells

“…Since clinical studies have found improved ovarian stimulation with mixtures of acidic and less acidic hFSH isoforms (16) it will be important to determine whether mixtures of hypo-glycosylated FSH and fully-glycosylated FSH contribute to enhanced or diminished biological responses. Understanding how FSH glycoforms direct activities in multiple FSH target tissues [ovary, bone (33,34), endothelium (35), uterus and placenta (36,37)] offers a unique opportunity to develop novel approaches for diagnosis and treatments to improve fertility and reduce age associated morbidity.…”