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Exp Clin Endocrinol Diabetes 2004; 112(8): 451-457
DOI: 10.1055/s-2004-821205
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Ovarian Function and Morphology after Deletion of the DARPP-32 Gene in Mice

A. Mayerhofer1 , S. Fritz1 , S. Mani2 , T. Rajendra Kumar3 , A. Thalhammer1 , P. Ingrassia4 , A. A. Fienberg4 , P. Greengard4
  • 1Anatomisches Institut der Universität München, Munich, Germany
  • 2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
  • 3Department of Pathology, Baylor College of Medicine, Houston, TX, USA
  • 4Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA
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Publication History

Publication Date:
16 September 2004 (online)

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Abstract

A plethora of systemic and local signaling molecules regulate ovarian function, but how different signaling molecules interact within an ovarian target cell is not known. Here we report that endocrine cells of the ovary express a phosphoprotein, DARPP-32 (dopamine and cyclic AMP-regulated phosphoprotein of Mr 32,000), which integrates signaling molecules in neurons. We thus hypothesized that DARPP-32 might act in a similar way in ovarian endocrine cells and therefore studied whether DARPP-32 gene deletion has consequences for ovarian functions in mice. Reproductive performance of adult mutants did not differ from wild-type females, as judged from numbers of litters and pups delivered. Similar steroid levels in mutant and wild-type mice ruled out gross abnormalities in the hypothalamic-pituitary-ovarian axis. However, an analysis of ovarian morphology, using serially sectioned ovaries, revealed several differences. Ovaries of young adult mutant mice at 2 - 3 months contained luteinized follicles, but fewer corpora lutea. At 5 - 6 months, large cysts were found in mutant mice, as well as reduced numbers of preantral follicles and antral follicles. Interstitial cell hypertrophy and degeneration was marked in all mutant ovaries at this age. Thus, while the lack of DARPP-32 does not overtly alter reproductive performance in adult mice, it is associated with progressive alterations and derangements of growth and development of ovarian follicles, suggesting premature ovarian ageing. This implies that ovarian DARPP-32 is involved in follicular development, presumably by integrating effects of signaling molecules, which act together to ensure efficient follicular development.

Key words

Follicle - corpus luteum - neurotransmitter - hormone - signal transduction

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Professor of Molecular Anatomy, M. D. Artur Mayerhofer

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