Activation of protein kinase C in the hypothalamic ventromedial nucleus or the midbrain central gray facilitates lordosis.
Many neurotransmitters and neuropeptides can act through the hypothalamic ventromedial nucleus (VMN) or midbrain central gray (MCG) to facilitate lordosis. Since these lordosis-facilitating agents can also stimulate the phosphoinositide (PI) second-messenger pathway, it was hypothesized that direct activation of this pathway can also potentiate the behavior. To evaluate this possibility, a phorbol ester, TPA (12-O-tetradecanoyl phorbol 13-acetate), was used to activate a key enzyme, protein kinase C (PKC), of the PI pathway in ovariectomized (OVX) rats either primed or not primed with estrogen. These female rats were paired with males for mating tests before and after an intracerebral infusion of TPA, and both the lordosis quotient (LQ) and the lordosis strength (LS) were measured. Bilateral infusion of TPA (5 micrograms/0.5 microliter or 0.2 microgram/0.2 microliter, but not 0.1 microgram/0.2 microliter/side) into the VMN or MCG of estrogen-primed subjects facilitated both LQ and LS in 30 min, peaked at 60-90 min, and the facilitation lasted for more than 180 min. This facilitatory effect of TPA was: (1) not observed in OVX rats not primed with estrogen; (2) not observed if the infused TPA did not reach both sides of the VMN or MCG; (3) not mimicked by 4 alpha-phorbol 12,13-didecanoate, which does not activate PKC; (4) blocked by PKC inhibitors (H7 10 mM or staurosporine 1 microM, 0.2 microliter/side), which by themselves did not facilitate lordosis; and (5) was not affected by pretreatment of the progestin antagonist RU486.(ABSTRACT TRUNCATED AT 250 WORDS)
Kow
L M
LM
Rockefeller University, New York, NY 10021-6399.
Brown
H E
HE
Pfaff
D W
DW
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000008:administration & dosage / Q000494:pharmacology; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007263:Infusions, Parenteral; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D010052:Ovariectomy; D010703:Phorbol Esters / Q000494:pharmacology; D011187:Posture; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D000470:Alkaloids; D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; D015735:Mifepristone; D004958:Estradiol; D002784:Cholesterol; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate