title: Nonclassical mechanisms of progesterone action in the brain: II. Role of calmodulin-dependent protein kinase II in progesterone-mediated signaling in the hypothalamus of female rats.
abstract: In addition to the activation of classical progestin receptor-dependent genomic pathway, progesterone (P) can activate nonclassical, membrane-initiated signaling pathways in the brain. We recently demonstrated rapid P activation of second-messenger kinases, protein kinase A, and protein kinase C in the ventromedial nucleus (VMN) and preoptic area (POA) of rat brain. To determine whether P can activate yet another Ca+2 dependent kinase, we examined the rapid P modulation of calcium and calmodulin-dependent protein kinase II (CaMKII) in the VMN and POA in female rats. A rapid P-initiated activation of CaMKII basal activity was observed in the VMN but not the POA at 30 min. Estradiol benzoate (EB) priming enhanced this CaMKII basal activity in both the VMN and POA. CaMKII protein levels and phosphorylation of Thr-286 moiety on CaMKII, however, remained unchanged with EB and/or P treatments, suggesting that the changes in the CaMKII kinase activity are due to rapid P modulation of the kinase activity and not its synthesis or autoactivation. Furthermore, intracerebroventricular (icv) administration of a CaMKII-specific inhibitor, KN-93, 30 min prior to the P infusion, in EB-primed, ovariectomized female rats inhibited CaMKII activation but not protein kinase A and protein kinase C activities. Interestingly, icv administration of KN-93 30 min prior to P infusion (icv) resulted in a reduction but not total inhibition of P-facilitated lordosis response in EB-primed female rats. These observations suggest a redundancy or, alternately, a hierarchy in the P-regulated activation of kinase signaling cascades in female reproductive behavior.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Bhuvana
authors.initials: B
authors.lastname: Balasubramanian
authors.forename: Wendy
authors.initials: W
authors.lastname: Portillo
authors.forename: Andrea
authors.initials: A
authors.lastname: Reyna
authors.forename: Jian Zhong
authors.initials: JZ
authors.lastname: Chen
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Moore
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Dash
authors.forename: Shaila K
authors.initials: SK
authors.lastname: Mani
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D010052:Ovariectomy; D010766:Phosphorylation / Q000187:drug effects; D011301:Preoptic Area / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D004958:Estradiol; D011374:Progesterone; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C074283:estradiol 3-benzoate