Publication Date:
2000-02-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mani, S K -- Fienberg, A A -- O'Callaghan, J P -- Snyder, G L -- Allen, P B -- Dash, P K -- Moore, A N -- Mitchell, A J -- Bibb, J -- Greengard, P -- O'Malley, B W -- MH49662/MH/NIMH NIH HHS/ -- MH57442/MH/NIMH NIH HHS/ -- NS 35457/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1053-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. smani@bcm.tmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669419" target="_blank"〉PubMed〈/a〉
Keywords:
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology
;
Animals
;
Cyclic AMP/metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Dopamine/pharmacology
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Dopamine Agonists/pharmacology
;
Dopamine and cAMP-Regulated Phosphoprotein 32
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Female
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Hypothalamus/metabolism
;
Injections, Intraventricular
;
Male
;
Mice
;
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/*metabolism
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Phosphorylation
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Posture
;
Progesterone/*pharmacology
;
Proteins/genetics/metabolism
;
Rats
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Rats, Sprague-Dawley
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Receptors, Progesterone/metabolism
;
Serotonin/pharmacology
;
Sexual Behavior, Animal/*drug effects
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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