Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis

Nature. 1996 Dec 5;384(6608):470-4. doi: 10.1038/384470a0.


THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / genetics
  • Cell Division / physiology
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP / physiology
  • Cyclin D2
  • Cyclins / genetics
  • Cyclins / physiology*
  • Female
  • Follicle Stimulating Hormone / physiology*
  • Gene Dosage
  • Gene Expression Regulation*
  • Gene Targeting
  • Granulosa Cells / cytology
  • Humans
  • Infertility, Female / genetics
  • Male
  • Mice
  • Ovarian Neoplasms / metabolism
  • Ovary / cytology
  • Ovary / physiology*
  • RNA, Messenger / metabolism
  • Spermatogenesis / physiology
  • Testicular Neoplasms / metabolism
  • Testis / cytology
  • Testis / physiology*
  • Tumor Cells, Cultured


  • CCND2 protein, human
  • Ccnd2 protein, mouse
  • Cyclin D2
  • Cyclins
  • RNA, Messenger
  • Colforsin
  • Follicle Stimulating Hormone
  • Cyclic AMP