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

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Science  11 Feb 2000:
Vol. 287, Issue 5455, pp. 1053-1056
DOI: 10.1126/science.287.5455.1053

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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.

  • * To whom correspondence should be addressed. E-mail: smani{at}

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

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