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

P Sicinski1, J L Donaher, Y Geng

  • 1Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.

Nature
|December 5, 1996
PubMed

Insights

The study reveals that cyclin D2 is essential for female fertility and male reproductive organ development in mice. Its absence causes sterility and hypoplastic testes, with implications for human ovarian and testicular cancers.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Reproductive Biology

Background:

  • D-type cyclins (D1, D2, D3) regulate the G1 phase of the mammalian cell cycle.
  • These cyclins are expressed redundantly in proliferating tissues, raising questions about their distinct roles.

Purpose of the Study:

  • To investigate the specific function of cyclin D2 in mammalian development and cell proliferation.
  • To understand the regulatory pathways controlling D-type cyclin expression.

Main Methods:

  • Gene targeting in embryonic stem cells to create cyclin D2-deficient mice.
  • Analysis of reproductive phenotypes in mutant males and females.
  • Investigation of cyclin D2 induction by follicle-stimulating hormone (FSH) in ovarian granulosa cells.
  • Examination of cyclin D2 mRNA levels in human ovarian and testicular tumors.

Main Results:

  • Cyclin D2-deficient females are sterile due to impaired ovarian granulosa cell proliferation in response to FSH.
  • Mutant males exhibit hypoplastic testes.
  • Cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway in granulosa cells.
  • Elevated cyclin D2 mRNA levels are found in some human ovarian and testicular tumors.

Conclusions:

  • Cyclin D2 plays a critical, non-redundant role in mammalian reproductive organ development.
  • Distinct intracellular signaling pathways regulate the expression of different D-type cyclins.
  • Cyclin D2 may be implicated in the development of certain human ovarian and testicular cancers.

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