Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice.
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.
Mani
S K
SK
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. smani@bcm.tmc.edu
Fienberg
A A
AA
O'Callaghan
J P
JP
Snyder
G L
GL
Allen
P B
PB
Dash
P K
PK
Moore
A N
AN
Mitchell
A J
AJ
Bibb
J
J
Greengard
P
P
O'Malley
B W
BW
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011187:Posture; D011374:Progesterone / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D015398:Signal Transduction
D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D011506:Proteins; D011980:Receptors, Progesterone; C073882:phosphoprotein phosphatase inhibitor 1; D012701:Serotonin; D011374:Progesterone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine