ABSTRACT
Dose-response curves for lordosis and proceptive behaviors were obtained for luteinizing hormone releasing hormone (LHRH), prostaglandin E2 (PGE2) and dibutyryl cyclic AMP (db-cAMP), by infusing them in the right lateral ventricle (i.c.v.) of ovariectomized (OVX) estradiol benzoate (E2B; 2 microg) treated rats. Two dose levels, one producing the maximal effect and the other one producing a submaximal response (approximately ED50) were selected for testing the capacity of Rp-cAMPS, a kinase A blocker, to modify the behavioral response to the three compounds. I.c.v. injections of Rp-cAMPS, significantly depressed both lordosis and proceptive responses induced by LHRH, PGE2 and db-cAMP. The results show that these agents use the cAMP-kinase A signaling pathway to elicit their stimulating effect on estrous behavior in the rat.
Subject(s)
Bucladesine/pharmacology , Cyclic AMP-Dependent Protein Kinases/physiology , Dinoprostone/pharmacology , Estrogens/pharmacology , Fertility Agents, Female/pharmacology , Gonadotropin-Releasing Hormone/pharmacology , Oxytocics/pharmacology , Sexual Behavior, Animal/drug effects , Animals , Cyclic AMP/analogs & derivatives , Cyclic AMP/pharmacology , Dose-Response Relationship, Drug , Estradiol/pharmacology , Female , Injections, Intraventricular , Ovariectomy , Posture , Rats , Signal Transduction/drug effects , Thionucleotides/pharmacologyABSTRACT
Dose response curves for lordosis behavior was obtained for progesterone (P) and its two ring A-reduced metabolites: 5alpha-pregnanedione (alpha-DHP) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl) by infusing these progestins in the right lateral ventricle (rlv) of ovariectomized (ovx) estradiol-treated rats (2 microg 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 alpha-DHP but failed to significantly inhibit that of 5alpha,3alpha-Pgl. The administration of H7 prevented the effect of both 5alpha-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; alpha-DHP through both kinase A and kinase C signaling pathways and 5alpha,3alpha-Pgl through the kinase C system.