In the ventral tegmental area, progestogens' membrane-mediated actions for lordosis of rats involve the second-messenger phospholipase C

Abstract

Steroid hormones have pervasive functional effects. Although steroids are generally known to have actions via binding to their cognate steroid receptors, it is becoming clearer that steroids can have non-traditional actions that do not require activation of cognate steroid receptors. We have found that progestogen-facilitated lordosis of rodents is enhanced by activation of dopamine type 1 (D1) or GABA(A) receptors and their downstream effectors, such as second messengers, in the ventral tegmental area (VTA). The role of phospholipase C in these effects is not clear. If progestins' actions through D1 and GABA(A) receptors in the VTA are mediated through PLC, then inhibiting PLC formation in the VTA, via infusions of U73122 (400nM/side), should reduce progestin (5alpha-pregnan-3alpha-ol-20-one; 3alpha,5alpha-THP; 100 or 200ng/side)-facilitated lordosis and its enhancement by D1 (SKF38393; 100ng/side) or GABA(A) (muscimol; 100ng/side) receptor agonists in ovariectomized, estradiol-primed rats. We found that 3alpha,5alpha-THP-, SKF38393-, and muscimol-facilitated lordosis was attenuated by infusions of the PLC inhibitor, U73122, but not vehicle, to the VTA. Thus, progestogens' non-traditional actions in the VTA to enhance lordosis through D1 and/or GABA(A) include activity of PLC.

Figure 1

In the VTA, SKF38393- or muscimol-mediated increases in 3α,5α -THP-facilitated lordosis quotients (LQs) of estradiol-primed rats are blocked by pre-treatment with the PLC inhibitor, U73122. # indicates a significant (P < 0.05) effect of 3α,5α -THP vs. vehicle infusions to enhance lordosis. * indicates a significant (P < 0.05) decrement produced by U73122 vs. vehicle infusions at that same 3α,5α -THP dosage (p<0.05). ** indicates a significant (P < 0.05) increase in 3α,5α -THP-facilitated lordosis following SKF38393 or muscimol compared to vehicle infusions (p<0.05).