Hormonal Control of the Cell Cycle in Ovarian Cells: Proliferation Versus Differentiation

Robker, Rebecca L.; Richards, Jo Anne S.

doi:10.1095/biolreprod59.3.476

Cited by 216 publications

(111 citation statements)

References 66 publications

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“…After follicles are established, a continuous process of proliferation and differentiation allows some of them to reach the preovulatory size (maximum differentiation level) and ovulate, but most ovarian follicles undergo a process of regression and death known as follicular atresia (Robker & Richards 1998a,b, Adams et al 2008.…”

Section: Cell Proliferation and Survival Mechanisms In Follicular Cystsmentioning

confidence: 99%

“…In humans as well as in cows, three D-type cyclins (cyclins D1, D2, and D3) have been identified (Zwijsen et al 1997, Yamauchi et al 2003. Although they have different functions according to the cell type, all of them appear to act by activating CDK4 and CDK6 (Zwijsen et al 1997, Robker & Richards 1998a, Yamauchi et al 2003. According to Robker & Richards (1998a,b), the expression of cyclin D2 and CDK4 in the ovary is confined to the granulosa layer, whereas cyclin D1 and cyclin D3 are expressed in both granulosa and theca layers, with higher expression levels in theca cells.…”

Section: R256 H H Ortega and Othersmentioning

confidence: 99%

“…According to Robker & Richards (1998a,b), the expression of cyclin D2 and CDK4 in the ovary is confined to the granulosa layer, whereas cyclin D1 and cyclin D3 are expressed in both granulosa and theca layers, with higher expression levels in theca cells. Cyclin E, another cyclin that seems to play a role in the ovary, acts as a positive regulator of cell cycle progression through activation of CDK2 (Reed 1996, Robker & Richards 1998a.…”

Section: R256 H H Ortega and Othersmentioning

confidence: 99%

See 2 more Smart Citations

Molecular aspects of bovine cystic ovarian disease pathogenesis

Ortega¹,

Marelli²,

Rey³

et al. 2015

Reproduction

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Cystic ovarian disease (COD) is one of the main causes of reproductive failure in cattle and causes severe economic loss to the dairy farm industry because it increases both days open in the post partum period and replacement rates due to infertility. This disease is the consequence of the failure of a mature follicle to ovulate at the time of ovulation in the estrous cycle. This review examines the evidence for the role of altered steroid and gonadotropin signaling systems and the proliferation/apoptosis balance in the ovary with cystic structures. This evidence suggests that changes in the expression of ovarian molecular components associated with these cellular mechanisms could play a fundamental role in the pathogenesis of COD. The evidence also shows that gonadotropin receptor expression in bovine cystic follicles is altered, which suggests that changes in the signaling system of gonadotropins could play a fundamental role in the pathogenesis of conditions characterized by altered ovulation, such as COD. Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with modifications in the expression of coregulatory proteins. These changes in the pathways of endocrine action would trigger the changes in proliferation and apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish abstract: A Spanish translation of this abstract is freely available at

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Section: Cell Proliferation and Survival Mechanisms In Follicular Cystsmentioning

confidence: 99%

Section: R256 H H Ortega and Othersmentioning

confidence: 99%

Section: R256 H H Ortega and Othersmentioning

confidence: 99%

See 1 more Smart Citation

Molecular aspects of bovine cystic ovarian disease pathogenesis

Ortega¹,

Marelli²,

Rey³

et al. 2015

Reproduction

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“…In the same study, E 2 also enhanced expression of other IGF-I pathway components and ER , indicating that E 2 and IGF-I may form an autocrine regulatory network within growing follicles. It has been suggested that FKHR expression may be linked to the proliferation of granulosa cells given that cells expressing FKHR were highly proliferative, expressed high levels of cyclin D2 (Robker & Richards 1998a) and ER (Sharma et al 1999) and showed increased staining for proliferating cell nuclear antigen (PCNA)/BrdU (Robker & Richards 1998b). The targets of FKHR in granulosa cells are not yet known.…”

Section: Folliculogenesismentioning

confidence: 99%

Estrogen actions in the ovary revisited

Britt¹,

Findlay²

2002

Journal of Endocrinology

160

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Estrogens are synonymous with fertility and infertility in mammals. Our knowledge of the biological actions of estrogens, however, is incomplete. Three recent developments have thrown new light on the actions of estrogens in mammalian reproduction that will lead to a greater understanding of their functions. They are (a) the identification of a second estrogen receptor, called ER , (b) the identification of ligand-specific ER coactivators and (c) mouse models with targeted disruption of the genes encoding both ER and the aromatase enzyme. These models provide for the first time animals which are either unable to respond to endogenous or exogenous estrogens (ER 'knockouts'), or can respond to exogenous estrogen but do not make endogenous estrogen (aromatase 'knockout' or ArKO). Furthermore, the ArKO mouse has provided a model to study the effects on the ovary of exogenous estrogens of plant and synthetic origin that are of clinical relevance. The data show that estrogens are essential for fertility but not for survival after birth or for the formation of the reproductive tract. This commentary focuses on the roles of estrogen in folliculogenesis and in the maintenance of the ovarian somatic cell phenotype in the mouse. We also hypothesize that the ER and ER may subserve the proliferative and differentiative actions of estrogen, respectively, within a follicle. In summary, estrogen is obligatory for normal folliculogenesis beyond the antral stage and for the maintenance of the female phenotype of the somatic cells within the ovaries. This clearly demonstrates a major role for sex steroids in somatic cell differentiation in the gonads of eutherian mammals and challenges the central paradigm that the ovary is the default gonad, arising due to the absence of testicular defining signals. Evidence is also provided for the plasticity of the adult female gonad. Understanding the mechanisms of estrogen actions will provide an insight into the regulation of reproductive disorders afflicting women today, notably ovarian dysfunction and the menopause.

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“…Granulosa cell proliferation is stimulated by exposure to estrogen, resulting in preovulatory follicles containing multiple layers of proliferating granulosa cells. At this stage, proliferating granulosa cells acquire luteinizing hormone receptors and the subsequent luteinizing hormone surge triggers granulosa cells of preovulatory follicles to exit the cell cycle (Robker and Richards, 1998). Estrogen maintains granulosa cells in experimental mice (Britt et al, 2002) and stimulates granulosa cell proliferation in small preantral follicles in hypophysectomized rats (Payne and Hellbaum, 1955); however, the molecular mechanisms underlying the estrogen regulation of cell proliferation remain unclear (Britt et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo

Bayne

Jones

et al. 2011

Protein Cell

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Estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues; however the mechanisms underlying the mitogenic actions of estrogen are not fully understood. Here we report that estrogen deficiency in mice caused by targeted disruption of the aromatase gene results in a significant inhibition of telomerase maintenance of telomeres in mouse ovaries in a tissue-specific manner. The inhibition entails a significant shortening of telomeres and compromised proliferation in the follicular granulosa cell compartment of ovary. Gene expression analysis showed decreased levels of proto-oncogene c-Myc and the telomerase catalytic subunit, telomerase reverse transcriptase (TERT), in response to estrogen deficiency. Estrogen replacement therapy led to increases in TERT gene expression, telomerase activity, telomere length and ovarian tissue growth, thereby reinstating ovary development to normal in four weeks. Our data demonstrate for the first time that telomere maintenance is the primary mechanism mediating the mitogenic effect of estrogen on ovarian granulosa cell proliferation by upregulating the genes of c-Myc and TERT in vivo. Estrogen deficiency or over-activity may cause ovarian tissue aging or tumorigenesis, respectively, through estrogen regulation of telomere remodeling.

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Hormonal Control of the Cell Cycle in Ovarian Cells: Proliferation Versus Differentiation

Cited by 216 publications

References 66 publications

Molecular aspects of bovine cystic ovarian disease pathogenesis

Molecular aspects of bovine cystic ovarian disease pathogenesis

Estrogen actions in the ovary revisited

Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo

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