Interactions between cAMP, PGE2 and Luteinizing Hormone Releasing Hormone (LHRH) in the rat hypothalamus

FERNANDEZ-SOLARI J; PRESTIFILIPPO JP; MOHN CE; DE LAURENTIIS A; DE LA CAL C; MCCANN SM; RETTORI V

San Diego, California, USA

Congreso; XXXV International Congress of Physiological Sciences; 2006

La fecha correcta de presentación en el Congreso es 2005 pero ha sido modificada para que el sistema lo considere dentro de mi período informado que abarca desde julio de 2005 hasta diciembre de 2006, por ser mi primer informe presentado como Investigador Asistente. Gonadotropin secretion by the pituitary gland is mainly under the control of LHRH. The mechanism proposed by us for the release of LHRH from the hypothalamus is: NO stimulated by norepinephrine activates cyclooxygenase with increase in PGE2 production that activates adenylyl cyclase (AC) with increase in cAMP that activates the exocytosis of LHRH. Also, NO stimulates GABA release that inhibits LHRH release. Therefore, we studied the interactions between cAMP, PGE2 and LHRH. Medial basal hypothalami (6-7/group) from adult male rats were incubated for 30 min in Krebs-Ringer buffer in the presence of different drugs and cAMP, PGE and LHRH were measured by RIA. Forskolin (FRSK, 76 µM), an AC activator and PGE2 (10-7M) increased LHRH release (6 fold p<0.01 and 4 fold p<0.001), respectively. SQ22536 (10-5M), a specific inhibitor of AC, partially blocked the release of LHRH induced by PGE2 (p<0.001). N6-monobutyril-cAMP (10-5,10-4,10-3M) and FRSK decreased PGE content (1 fold p<0.01 and 3 fold p<0.05), respectively. LHRH (10-9M) decreased (p<0.05) PGE release and increased (p<0.01) cAMP content. Bicuculline (10-4M),a GABAergic antagonist, increased (p<0.05) both, PGE and cAMP content. These results indicate that PGE2 and cAMP represent two complementary pathways for LHRH release that are mutually regulated and under GABAergic inhibitory tone. cAMP exerts a negative feedback on the hypothalamic PGE2 content and LHRH decreases PGE release but increases cAMP content. (Supported by PICT 99, 5-6117)