17 beta-estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP.
The process by which 17 beta-estradiol rapidly modulates the excitability of neurons in the ventromedial hypothalamus, a facilitation center of female sexual behavior and satiety center of feeding behavior, through mediation by cyclic nucleotides, was investigated by intracellular recording from the guinea pig brain slice preparations. Two types of short-term responses were produced by depolarization with decreased K+ conductance and hyperpolarization with increased K+ conductance. These two responses were enhanced by the phosphodiesterase inhibitor, isobutylmethylxanthine. However, the specific adenylate cyclase activator, forskolin, enhanced only the depolarization. The analogue of cyclic adenosine 3',5'-monophosphate (cAMP), 8-bromo-cAMP, induced only depolarization, the ionic mechanism of which was similar to that of 17 beta-estradiol. In addition, the possibility of non-specific effects of cyclic nucleotides was precluded by an experiment using an analogue of cyclic guanosine 3',5'-monophosphate (cGMP), 8-bromo-cGMP, which hyperpolarized neurons. Thus, the present study strongly suggests that the production of depolarizing responses of neurons in the hypothalamus produced by estradiol is specifically mediated through cAMP.
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
T
T
Minami
Y
Y
Oomura
J
J
Nabekura
A
A
Fukuda
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004343:Drug Implants; D004553:Electric Conductivity; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D011188:Potassium / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives*
D004343:Drug Implants; D007093:Imidazoles; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D004958:Estradiol; C029899:imidazole; D013806:Theophylline; D000242:Cyclic AMP; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine