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Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice

Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice

Authors :
Bert W. O'Malley
James P. O'Callaghan
James A. Bibb
Patrick B. Allen
Gretchen L. Snyder
Andrea Mitchell
Allen A. Fienberg
Paul Greengard
Pramod K. Dash
Shailaja K. Mani
A. N. Moore
Source :
Science (New York, N.Y.). 287(5455)
Publication Year :
2000

Abstract

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 D 1 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.

Details

ISSN :
00368075
Volume :
287
Issue :
5455
Database :
OpenAIRE
Journal :
Science (New York, N.Y.)
Accession number :
edsair.doi.dedup.....b1d840e65e045d8ce919d0b24d5ef937