Differential effect of kinase A and C blockers on lordosis facilitation by progesterone and its metabolites in ovariectomized estrogen-primed rats

Abstract

Dose response curves for lordosis behavior was obtained for progesterone (P) and its two ring A–reduced metabolites: 5α-pregnanedione (α-DHP) and 5α,3α-pregnanolone (5α,3α-Pgl) by infusing these progestins in the right lateral ventricle (rlv) of ovariectomized (ovx) estradiol–treated rats (2 μg estradiol benzoate; EB), 40 h before intracerebro–ventricular (icv) injection. Effective doses 50 (ED50) revealed that ring A–reduced progestins were more potent than P itself to induce lordosis behavior. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (ED50–ED60), were selected for testing the capacity of RpAMPS, a kinase A blocker, and H7, a kinase C blocker, to modify the response to the three progestins. rlv injection of RpAMPS significantly depressed the lordosis response to the two dose levels of P and α-DHP but failed to significantly inhibit that of 5α,3α-Pgl. The administration of H7 prevented the effect of both 5α–reduced progestins without affecting the response to P. The results suggest that P and its ring A–reduced metabolites stimulate lordosis behavior through different cellular mechanisms: P acting mainly through the cAMP-kinase system; α-DHP through both kinase A and kinase C signaling pathways and 5α,3α-Pgl through the kinase C system.