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 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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
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Animals
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dopamine / pharmacology
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Dopamine Agonists / pharmacology
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Female
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Hypothalamus / metabolism
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Injections, Intraventricular
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nerve Tissue Proteins*
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Oligonucleotides, Antisense / pharmacology
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Phosphorylation
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Posture
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Progesterone / pharmacology*
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Proteins / genetics
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Proteins / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Progesterone / metabolism
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Serotonin / pharmacology
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Sexual Behavior, Animal / drug effects*
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Signal Transduction
Substances
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Dopamine Agonists
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Nerve Tissue Proteins
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Oligonucleotides, Antisense
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Phosphoproteins
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Proteins
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Receptors, Progesterone
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phosphoprotein phosphatase inhibitor 1
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Serotonin
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Progesterone
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Dopamine