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

S K Mani; A A Fienberg; J P O'Callaghan; G L Snyder; P B Allen; P K Dash; A N Moore; A J Mitchell; J Bibb; P Greengard; B W O'Malley

doi:10.1126/science.287.5455.1053

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

Science. 2000 Feb 11;287(5455):1053-6. doi: 10.1126/science.287.5455.1053.

Authors

S K Mani¹, A A Fienberg, J P O'Callaghan, G L Snyder, P B Allen, P K Dash, A N Moore, A J Mitchell, J Bibb, P Greengard, B W O'Malley

Affiliation

¹ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. smani@bcm.tmc.edu

PMID: 10669419
DOI: 10.1126/science.287.5455.1053

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

Research Support, U.S. Gov't, P.H.S.

MeSH terms

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
Dopamine Agonists / pharmacology
Dopamine and cAMP-Regulated Phosphoprotein 32
Female
Hypothalamus / metabolism
Injections, Intraventricular
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins*
Oligonucleotides, Antisense / pharmacology
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Phosphorylation
Posture
Progesterone / pharmacology*
Proteins / genetics
Proteins / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Progesterone / metabolism
Serotonin / pharmacology
Sexual Behavior, Animal / drug effects*
Signal Transduction

Substances

Dopamine Agonists
Dopamine and cAMP-Regulated Phosphoprotein 32
Nerve Tissue Proteins
Oligonucleotides, Antisense
Phosphoproteins
Proteins
Receptors, Progesterone
phosphoprotein phosphatase inhibitor 1
Serotonin
Progesterone
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Dopamine

Grants and funding

etc