RGD Reference Report - Regulation of cyclin D2 expression and degradation by follicle-stimulating hormone during rat granulosa cell proliferation in vitro. - Rat Genome Database

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Regulation of cyclin D2 expression and degradation by follicle-stimulating hormone during rat granulosa cell proliferation in vitro.

Authors: Han, Y  Xia, G  Tsang, BK 
Citation: Han Y, etal., Biol Reprod. 2013 Mar 7;88(3):57. doi: 10.1095/biolreprod.112.105106. Print 2013 Mar.
RGD ID: 9685537
Pubmed: PMID:23349233   (View Abstract at PubMed)
DOI: DOI:10.1095/biolreprod.112.105106   (Journal Full-text)

Cyclin D2 (CCND2, encoded by Ccnd2) plays an important role in the induction of early-to-mid G1 phase transition and is required for granulosa cell proliferation during ovarian folliculogenesis. In the present study, we investigated the role of follicle-stimulating hormone (FSH) in the regulation of cyclin D2 expression and degradation during rat granulosa cell proliferation in vitro. FSH acutely increased granulosa cell Ccnd2 mRNA abundance and CCND2 protein content as well as proliferation. FSH-induced granulosa cell CCND2 protein content and proliferation were mimicked by forskolin and attenuated by inhibitors of protein kinase A (PKA; H89) and phosphatidylinositol 3-kinase (PI3K; LY294002) as well as PKA catalytic subunit (PRKACA) small interfering RNA (siRNA) and dominant-negative Akt (dn-Akt) but were not affected by mitogen-activated protein kinase kinase 1/2 (MEK1/2; U0126). Interestingly, FSH also enhanced CCND2 protein degradation in granulosa cells, a process involving a PKA-mediated ubiquitin-proteasome degradation pathway. Taken together, these results demonstrate that FSH acutely regulated CCND2 expression through both PKA and PI3K signaling pathways during granulosa cell proliferation and also accelerated its ubiquitination-proteasomal degradation, which may prevent overstimulation of granulosa cell proliferation and follicular growth.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell population proliferation  IMP 9685537 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkaca  (protein kinase cAMP-activated catalytic subunit alpha)


Additional Information