[Abstract Title]. - Society for Neuroscience

Poster
278. Sex Differences I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 278.10/MM3
Topic: E.01.e. Sexual differences
Support: NIH MH52716-010 to MMM
Title: PGE2 mediates the perinatal organization of male sexual behavior: Is protein kinase A
signaling required?
Authors: *C. L. WRIGHT 1 , M. M. MCCARTHY 2,3 ;
1 Program Neurosci, Univ. Maryland, Baltimore, MD; 2 Program in Neurosci., 3 Departments of
Physiol. and Psychiatry, Univ. of Maryland, Sch. of Med., Baltimore, MD
Abstract: Masculinization of the brain and behavior is mediated by gonadal steroids during a
sensitive perinatal window. In the rat, estradiol aromatized from testosterone masculinizes the
brain by upregulating the cyclooxygenase enzymes (COX-1 & -2) and their major product,
prostaglandin E2 (PGE2), in the preoptic area. Consequently, PGE2 induces permanent changes
in preoptic area neuroanatomy, including a two-fold increase in the density of dendritic spines
and the level of spinophilin protein (Amateau and McCarthy, 2004, Nat. Neurosci.). Spinophilin
is enriched in dendritic spines and is an excellent proxy marker for dendritic spine formation. We
recently determined that the EP2 and EP4 receptors for PGE2 are necessary and sufficient for the
organization of male sexual behavior. EP2 and EP4 are coupled to Gs-proteins which increase
cAMP production by adenylyl cyclase and subsequently recruit protein kinase A (PKA)
phosphorylation of substrates. We have now tested if PKA signaling is necessary for the
induction of neonatal POA spinophilin protein and organization of male sexual behavior by
utilizing the cell permeable form of an AKAP-PKA binding inhibitor, Ht31. PKA signaling
depends upon its coupling to AKAP proteins which localize the enzyme near both adenylyl
cyclase and enzymatic targets. Ht31 mimics the AKAP binding sequence for PKA, dissociating
the two molecules. With PKA bound to Ht31, PKA is no longer near its substrate, thereby
inhibiting signaling. Neonatal females were injected intracerebroventricularly with Ht31 then
PGE2 on day of birth and half were assayed neonatally for the induction of spinophilin. The
remaining animals were grown until adulthood, implanted with silastic testosterone capsules, and
assessed for the expression of male sexual behavior. Treatment with Ht31 prevented the
induction of neonatal POA spinophilin protein in response to PGE2 exposure, suggesting that
PKA is necessary for changes in POA neuroanatomy including the formation of dendritic spines.
The pending behavioral results will determine if PKA signaling is necessary for the organization
of male sexual behavior in response to PGE2 exposure.