The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen

C.SCORTICATI,; J.FERNANDEZ SOLARI,; A. DE LAURENTIIS,; C.MOHN,; PRESTIFILIPPO JP,; M.LASAGA,; A. SEILICOVICH; S BILLI,; A FRANCHI,

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2004 vol. 101 p. 11891 - 11896

0027-8424

Because -9-tetrahydrocannabinol (THC) inhibited luteinizing hormone- releasing hormone (LHRH) in male rats, we hypothesized that the endocannabinoid, anandamide (AEA), would act similarly. AEA microinjected intracerebroventricularly (i.c.v.) decreased plasma luteinizing hormone (LH) at 30 min in comparison to values in controls (P < 0.001). The cannabinoid receptor 1 (CB1-r)-specific antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)- 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)- 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)- 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)- 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated 4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated a significant elevation in plasma LH (P < 0.01). AEA (109 M) decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated decreased LHRH release from medial basal hypothalami incubated P < 0.001). The cannabinoid receptor 1 (CB1-r)-specific antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)- 4-methyl-1H