BMP-2 and -6 modulate porcine theca cell function alone and co-cultured with granulosa cells

Brankin, Victoria; Quinn, Ruth L.; Webb, Robert I.; Hunter, M. G.

doi:10.1016/j.domaniend.2005.04.001

Cited by 30 publications

(20 citation statements)

References 33 publications

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“…In the rat ovary, BMP6 inhibits FSH responsiveness by suppressing adenylyl cyclase activity (Miyoshi et al 2007). Similar inhibitory effects of BMP6 on FSH responsiveness have been reported in cattle (Glister et al 2004) and pigs (Brankin et al 2005). By comparison, BMP6 treatment was determined to increase FSHR mRNA expression in cultured human granulosa cells (Shi et al 2009).…”

Section: Introductionmentioning

confidence: 74%

Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles

2012

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A growing body of literature provides evidence of a prominent role for bone morphogenetic proteins (BMPs) in regulating various stages of ovarian follicle development. Several actions for BMP6 have been previously reported in the hen ovary, yet only within postselection (preovulatory) follicles. The initial hypothesis tested herein is that BMP6 increases FSH receptor (FSHR) mRNA expression within the granulosa layer of prehierarchal (6-8 mm) follicles (6-8 GC). BMP6 mRNA is expressed at higher levels within undifferentiated (1-8 mm) follicles compared with selected (R9 mm) follicles. Recombinant human (rh) BMP6 initiates SMAD1, 5, 8 signaling in cultured 6-8 GC and promotes FSHR mRNA expression in a dose-related fashion. In addition, a 21 h preculture with rhBMP6 followed by a 3 h challenge with FSH increases cAMP accumulation, STAR (StAR) expression, and progesterone production. Interestingly, rhBMP6 also increases expression of anti-Mü llerian hormone (AMH) mRNA in cultured 6-8 GC. This related BMP family member has previously been implicated in negatively regulating FSH responsiveness during follicle development. Considering these data, we propose that among the paracrine and/or autocrine actions of BMP6 within prehierarchal follicles is the maintenance of both FSHR and AMH mRNA expression. We predict that before follicle selection, one action of AMH within granulosa cells from 6 to 8 mm follicles is to help suppress FSHR signaling and prevent premature granulosa cell differentiation. At the time of selection, we speculate that the yet undefined signal directly responsible for selection initiates FSH responsiveness. As a result, FSH signaling suppresses AMH expression and initiates the differentiation of granulosa within the selected follicle.

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Section: Introductionmentioning

confidence: 74%

Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles

2012

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“…The BMP signaling pathway plays a crucial role in female fertility in mammals by regulating steroidogenesis and mitogenesis in granulosa cells (GCs) (Shimasaki et al, , 2004. BMP-2, BMP-4, BMP-6, BMP-7, and BMP-15 can inhibit the secretion of 3-β-hydroxysteroid dehydrogenase and progesterone, and the expression of the follicle-stimulating hormone (FSH) receptor in different cells respectively (Shimasaki et al, 1999;Lee et al, 2001;Otsuka et al, 2001a,b;Nilsson and Skinner, 2003;Brankin et al, 2005;Miyoshi et al, 2006); in addition, BMP-7 was quite potent in promoting primordial follicles into primary and secondary follicles (Lee et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Effect of BMPRIB gene silencing by siRNA on apoptosis and steroidogenesis of porcine granulosa cells

Zhao¹,

Li²,

Wang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Bone morphogenetic proteins (BMPs) are the key factors in maintaining cell growth and differentiation in ovaries. BMPs initiate signaling by assembling BMP receptors and activating Smads, which in turn alter the expression of target genes. However, little is known about the effect of the deletion of the Bone morphogenetic protein receptor type IB (BMPRIB) on porcine granulosa cell (GCs). The objective of this study was to determine the effects of BMPRIB gene silencing, by small interfering RNA (siRNA), on the apoptosis and steroidogenesis of porcine GCs, and the expression of cell cycle-related and apoptosis-related genes. Results indicate that the BMPRIB siRNA caused specific inhibition of BMPRIB mRNA expression after transfection. Knockdown of the BMPRIB gene significantly inhibited porcine GCs proliferation and estradiol production, while inducing apoptosis of porcine GCs. Additionally, the declined expression of the BMPRIB gene changed the expressions of CylinD2, Cdk2, Bcl-2, and Cyp19a1. These

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“…For instance, members of the transforming growth factor-β (TGF-β) superfamily of proteins are well-established regulators of ovarian steroidogenesis and follicle development (11, 12). In regards to androgen production, bone morphogenetic protein (BMP)-6 potently suppressed basal and LH-induced secretion in ovine (13), bovine (14), porcine (15) and human TCs (16). TGF-β1, which is expressed by GCs and TCs (15), suppressed androgen secretion from rat (17) and human TCs (18).…”

Section: Introductionmentioning

confidence: 99%

“…In regards to androgen production, bone morphogenetic protein (BMP)-6 potently suppressed basal and LH-induced secretion in ovine (13), bovine (14), porcine (15) and human TCs (16). TGF-β1, which is expressed by GCs and TCs (15), suppressed androgen secretion from rat (17) and human TCs (18). Activin decreased whereas inhibin increased androgen secretion from human (16, 19), rat (10), and bovine (20) TCs.…”

Section: Introductionmentioning

confidence: 99%

Paracrine regulation of theca androgen production by granulosa cells in the ovary

Hoang

McTavish

Chang

et al. 2013

Fertility and Sterility

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Objective To test whether and to what extent inhibin mediates Cyp17 mRNA expression in theca cells (TCs) in response to FSH stimulation of granulosa cells (GCs). Design Ex-vivo and in vitro experimental study. Setting Department of Reproductive Medicine, University of California, San Diego, School of Medicine. Animal(s) Immature female Sprague Dawley rats. Interventions(s) Ovarian tissue explants and isolated theca-interstitial cell (TIC) preparations with or without GCs were treated with FSH, inhibin, inhibin antibody or β-glycan antibody. Main Outcome Measure(s) As a key enzyme in androgen production, Cyp17 mRNA levels were measured by real-time RT-PCR. Result(s) After 24 hours, Cyp17 mRNA expression was dose-dependently increased by FSH in ovarian tissue explants and TICs, suggesting that paracrine factor(s) secreted from GCs in response to FSH mediates Cyp17 mRNA expression in TCs. Antibodies against inhibin and inhibin co-receptor, β-glycan, blocked the stimulatory effect of FSH on Cyp17 mRNA expression. However, inhibin alone did not increase Cyp17 mRNA level to the same extent. Conclusion(s) These findings suggest a role for inhibin in the paracrine regulation of TC Cyp17 mRNA expression by GCs influenced by FSH; however, other paracrine factors produced by GCs by virtue of FSH seem to be required.

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BMP-2 and -6 modulate porcine theca cell function alone and co-cultured with granulosa cells

Cited by 30 publications

References 33 publications

Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles

Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles

Effect of BMPRIB gene silencing by siRNA on apoptosis and steroidogenesis of porcine granulosa cells

Paracrine regulation of theca androgen production by granulosa cells in the ovary

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