Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome

Norman, Robert J.; Milner, C.R.; Groome, Nigel P.; Robertson, David

doi:10.1093/humrep/16.4.668

Cited by 78 publications

(42 citation statements)

References 31 publications

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“…Body weight has been shown to affect the follistatin level in women with PCOS (8); however, such an association between body weight and follistatin level was not found in another study (7). With regression analysis, in this study, we showed that the circulating follistatin level was still significantly associated with hsCRP in the PCOS and control groups after further adjustment for insulin sensitivity, BMI, and FAI.…”

contrasting

confidence: 65%

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The relationship between follistatin and chronic low-grade inflammation in women with polycystic ovary syndrome

Chen¹,

Chen²,

Ho³

et al. 2009

Fertility and Sterility

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contrasting

confidence: 65%

“…Serum circulating follistatin levels have been reported to be higher in women with PCOS than in those without PCOS (7,8). However, no significant difference in follistatin concentrations was measured in follicular fluids between follicles obtained from healthy controls and those from women with PCOS (9).…”

mentioning

confidence: 89%

The relationship between follistatin and chronic low-grade inflammation in women with polycystic ovary syndrome

Chen¹,

Chen²,

Ho³

et al. 2009

Fertility and Sterility

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“…Given the marked inhibitory effect of activins and BMPs on thecal androgen production, it has also been suggested (Glister et al 2005) that compromised intraovarian activin and/or BMP signalling, perhaps due to overexpression or activity of extracellular BPs could by a contributory factor in polycystic ovarian syndrome (PCOS), a condition associated with ovarian androgen excess and impaired preovulatory follicle development (Mason 2000). Consistent with this notion, there have been several reports of raised circulating follistatin levels in women with PCOS (Norman et al 2001, Chen et al 2009). However, we are not aware of any evidence implicating altered expression of other extracellular BMP-BPs in the aetiology of PCOS.…”

Section: Bmp-binding Proteins and Follicle Developmentmentioning

confidence: 96%

Granulosal and thecal expression of bone morphogenetic protein- and activin-binding protein mRNA transcripts during bovine follicle development and factors modulating their expression in vitro

Glister¹,

Satchell²,

Knight³

2011

Reproduction

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Evidence supports local roles for transforming growth factor b superfamily members including activins and bone morphogenetic proteins (BMP) in follicle development. Access of these ligands to signalling receptors is likely modulated by extracellular binding proteins (BP). In this study, we compared ex vivo expression of four BPs (chordin, gremlin, noggin and follistatin) in granulosal (GC) and theca interna (TC) compartments of developing bovine antral follicles (1-18 mm). Effects of FSH and IGF on BMP and BP expression by cultured GC, and effects of LH and BMPs on BP expression by cultured TC were also examined. Follicular expression of all four BP transcripts was higher in GC than TC compartments (P!0.001) a finding confirmed by immunohistochemistry. Follicle category affected (P!0.01) gremlin and follistatin mRNA abundance, with a significant cell-type!follicle category interaction for chordin, follistatin and noggin. Noggin transcript abundance was lower (P!0.05) in GC of large 'E-active' than 'E-inactive' follicles while follistatin mRNA level was higher (P!0.01). FSH enhanced CYP19, FSHR, INHBA and follistatin by GC without affecting BMP or BMP-BP expression. IGF increased CYP19 and follistatin, reduced BMP4, noggin and gremlin but did not affect chordin or FSHR mRNA levels. LH increased TC androgen secretion but had no effect on BMP or BP expression. BMPs uniformly suppressed TC androgen production whilst increasing chordin, noggin and gremlin mRNA levels up to 20-fold (P!0.01). These findings support the hypothesis that extracellular BP, mostly from GC, contribute to the regulation of intrafollicular BMP/activin signalling. Enhancement of thecal BP expression by BMP implies an autoregulatory feedback role to prevent excessive signalling.

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“…Consequently a shift from an activin-dominant to an inhibin-dominant microenvironment occurs during follicle growth [76], which is impaired in some, but not all, PCOS follicles [77][78][79]. Moreover, low activin A levels and high follistatin levels in the circulation of some PCOS patients [80,81] correspond with diminished intrafollicular activin in prenatally Ttreated sheep [26] and activin β subunit responsiveness to steroid in neonatal mice [82]. These findings emphasize the further need to understand how TGFβ family members affect intraovarian paracrine signaling during fetal developmental programming.…”

Section: Impaired Follicle Growthmentioning

confidence: 99%

Polycystic ovary syndrome and its developmental origins

Dumesic

Abbott

Padmanabhan

2007

Rev Endocr Metab Disord

254

168

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The prenatal testosterone (T)-treated adult female rhesus monkey is one animal model of polycystic ovary syndrome (PCOS) in women, with early prenatal T excess programming a permanent PCOS-like phenotype characterized by luteinizing hormone (LH) hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess from increased abdominal adiposity. These combined reproductive and metabolic abnormalities are associated with ovarian hyperandrogenism and follicular arrest in adulthood, as well as premature follicle differentiation and impaired embryo development during gonadotropin therapy for in vitro fertilization (IVF). A second animal model for PCOS, the prenatal T-treated sheep also is characterized by LH hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback, persistent follicles and insulin resistance, but also is associated with intrauterine growth retardation and compensatory growth after birth. The ability of prenatal T excess in both species to alter the developmental trajectory of multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programs target tissue differentiation, raising the possibility that T excess in human fetal development promotes PCOS in adulthood. Such a hypothesis must include data from clinical studies of PCOS women to clarify the homology between these PCOS-like animal models and PCOS per se in reproductive and metabolic function. Future studies should develop new clinical strategies that improve pregnancy outcome and minimize pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus as well as minimize transgenerational susceptibility to adult PCOS and its metabolic derangements in male close relatives.

show abstract

Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome

Cited by 78 publications

References 31 publications

The relationship between follistatin and chronic low-grade inflammation in women with polycystic ovary syndrome

The relationship between follistatin and chronic low-grade inflammation in women with polycystic ovary syndrome

Granulosal and thecal expression of bone morphogenetic protein- and activin-binding protein mRNA transcripts during bovine follicle development and factors modulating their expression in vitro

Polycystic ovary syndrome and its developmental origins

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