| First Author | Oberlander JG | Year | 2012 |
| Journal | Neuroscience | Volume | 226 |
| Pages | 397-410 | PubMed ID | 22989919 |
| Mgi Jnum | J:192470 | Mgi Id | MGI:5465226 |
| Doi | 10.1016/j.neuroscience.2012.09.014 | Citation | Oberlander JG, et al. (2012) Estrous cycle variations in GABA(A) receptor phosphorylation enable rapid modulation by anabolic androgenic steroids in the medial preoptic area. Neuroscience 226:397-410 |
| abstractText | Anabolic androgenic steroids (AAS), synthetic testosterone derivatives that are used for ergogenic purposes, alter neurotransmission and behaviors mediated by GABA(A) receptors. Some of these effects may reflect direct and rapid action of these synthetic steroids at the receptor. The ability of other natural allosteric steroid modulators to alter GABA(A) receptor-mediated currents is dependent upon the phosphorylation state of the receptor complex. Here we show that phosphorylation of the GABA(A) receptor complex immunoprecipitated by beta(2)/beta(3) subunit-specific antibodies from the medial preoptic area (mPOA) of the mouse varies across the estrous cycle; with levels being significantly lower in estrus. Acute exposure to the AAS, 17alpha-methyltestosterone (17alpha-MeT), had no effect on the amplitude or kinetics of inhibitory postsynaptic currents in the mPOA of estrous mice when phosphorylation was low, but increased the amplitude of these currents from mice in diestrus, when it was high. Inclusion of the protein kinase C (PKC) inhibitor, calphostin, in the recording pipette eliminated the ability of 17alpha-MeT to enhance currents from diestrous animals, suggesting that PKC-receptor phosphorylation is critical for the allosteric modulation elicited by AAS during this phase. In addition, a single injection of 17alpha-MeT was found to impair an mPOA-mediated behavior (nest building) in diestrus, but not in estrus. PKC is known to target specific serine residues in the beta(3) subunit of the GABA(A) receptor. Although phosphorylation of these beta(3) serine residues showed a similar profile across the cycle, as did phosphoserine in mPOA lysates immunoprecipitated with beta2/beta3 antibody (lower in estrus than in diestrus or proestrus), the differences were not significant. These data suggest that the phosphorylation state of the receptor complex regulates both the ability of AAS to modulate receptor function in the mPOA and the expression of a simple mPOA-dependent behavior through a PKC-dependent mechanism that involves the beta(3) subunit and other sites within the GABA(A) receptor complex. |
