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Science 287 (5455): 1053-1056

Copyright © 2000 by the American Association for the Advancement of Science

Requirement for DARPP-32 in Progesterone-Facilitated Sexual Receptivity in Female Rats and Mice

S. K. Mani, 1* A. A. Fienberg, 2dagger J. P. O'Callaghan, 3 G. L. Snyder, 2 P. B. Allen, 2 P. K. Dash, 4 A. N. Moore, 4 A. J. Mitchell, 1 J. Bibb, 2 P. Greengard, 2 B. W. O'Malley 1

DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.

1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
2 Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021, USA.
3 Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
4 Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, TX 77030, USA.
*   To whom correspondence should be addressed. E-mail: smani{at}bcm.tmc.edu

dagger    Present address: The Novartis Institute for Functional Genomics, San Diego, CA, USA.

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