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
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DOI:
10.1126/science.287.5455.1053
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发表时间:
2000-02-11
期刊:
影响因子:
56.9
通讯作者:
O'Malley, BW
中科院分区:
文献类型:
--
作者:
Mani, SK;Fienberg, AA;O'Malley, BW
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.