anandamide and Pituitary-Neoplasms

Patients with craniopharyngioma (CP) frequently suffer from morbid obesity. Endocannabinoids (ECs) are involved in weight gain and rewarding behavior but have not been investigated in this context.. Cross-sectional single-center study.. Eighteen patients with CP and 16 age- and sex-matched controls were included. Differences in endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and endocannabinoid-like molecules (oleoyl ethanolamide (OEA), palmitoylethanolamide (PEA), and arachidonic acid (AA) were measured at baseline and following endurance exercise. We further explored ECs-dynamics in relation to markers of HPA-axis activity (ACTH, cortisol, copeptin) and hypothalamic damage.. Under resting conditions, independent of differences in BMI, 2-AG levels were more than twice as high in CP patients compared to controls. In contrast, 2-AG and OEA level increased in response to exercise in controls but not in CP patients, while AEA levels decreased in controls. As expected, exercise increased ACTH and copeptin levels in controls only. In a mixed model analysis across time and group, HPA measures did not provide additional information for explaining differences in 2-AG levels. However, AEA levels were negatively influenced by ACTH and copeptin levels, while OEA levels were negatively predicted by copeptin levels only. There were no significant differences in endocannabinoids depending on hypothalamic involvement.. Patients with CP show signs of a dysregulated endocannabinoid system under resting conditions as well as following exercise in comparison to healthy controls. Increased 2-AG levels under resting conditions and the missing response to physical activity could contribute to the metabolic phenotype of CP patients.

Topics: Adrenocorticotropic Hormone; Adult; Arachidonic Acid; Arachidonic Acids; Case-Control Studies; Craniopharyngioma; Cross-Sectional Studies; Endocannabinoids; Endurance Training; Exercise; Female; Glycerides; Glycopeptides; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Middle Aged; Oleic Acids; Pituitary Neoplasms; Polyunsaturated Alkamides; Young Adult

Linoleoylamide is physiological constituent of neurons. The effects of this agent, also a sleep-inducing agent, on ion currents in pituitary GH(3) cells were investigated. Hyperpolarization-elicited K(+) currents in GH(3) cells bathed in a high-K(+), Ca(2+)-free solution were studied to determine the effects of linoleoylamide and other related compounds on the I(K(IR)) that was sensitive to inhibition by E-4031 and identified as an erg (ether-à-go-go-related-gene) current. Linoleoylamide suppressed the amplitude of I(K(IR)) in a concentration-dependent manner with an IC(50) value of 5 microM. Oleamide (20 microM) inhibited the amplitude of I(K(IR)), while neither arachidonic acid (20 microM) nor 14,15-epoxyeicosatrienoic acid (20 microM) had an effect on it. In GH(3) cells incubated with anandamide (20 microM) or arachidonic acid (20 microM), the linoleoylamide-induced inhibition of I(K(IR)) remained unaltered. In inside-out patches, arachidonic acid (20 microM) and 14,15-epoxyeicosatrienoic acid (20 microM) stimulated large-conductance Ca(2+)-activated K(+) channels; however, linoleoylamide (20 microM) had little or no effect on them. Under current-clamp mode, linoleoylamide (20 microM) increased the firing rate. In IMR-32 neuroblastoma cells, linoleoylamide also suppressed I(K(IR)). This study provides the evidence that linoleoylamide has a depressant effect on the erg current, and suggests that this effect may affect hormonal secretion.

Topics: 8,11,14-Eicosatrienoic Acid; alpha-Linolenic Acid; Amides; Animals; Arachidonic Acid; Arachidonic Acids; Calcium; Calcium Channels, L-Type; Dose-Response Relationship, Drug; Endocannabinoids; Humans; Hydantoins; Imidazoles; Imidazolidines; Infant, Newborn; Linoleic Acids; Membrane Potentials; Neuroblastoma; Patch-Clamp Techniques; Piperazines; Piperidines; Pituitary Neoplasms; Polyunsaturated Alkamides; Potassium Channels; Pyridines; Tumor Cells, Cultured