et al.. Pulsatile cerebrospinal fluid and plasma ghrelin in relation to growth hormone secretion and food intake in the sheep.. Journal of Neuroendocrinology, Wiley, 2008, 20 (10), pp.1138-46. 10.1111/j.1365-2826.2008 Pulsatile CSF and plasma ghrelin in relation with GH secretion and food intake in the sheep.Grouselle Dominique, * Chaillou Elodie, *Caraty Alain, Bluet-Pajot Marie-Therese, Zizzari Philippe, *Tillet Yves, Epelbaum Jacques. Key words : plasma, CSF, pulsatile patterns.
AddressesElodie Chaillou and Dominique Grouselle contributed equally to this work.The definitive version is available at www.blackwell-synergy.com
ABSTRACTAs in other species, exogenous administration of ghrelin, an endogenous ligand for the GH secretagogue receptors can stimulates feeding behaviour and GH secretion in the sheep. However the importance of endogenous ghrelin for these two functions as well as its central or peripheral origin remained to be established. In this study, CSF ghrelin concentrations were measured in five anoestrous ewes and found to be more than 1000-fold lower than circulating plasma levels, in keeping with the even lower concentration in hypothalamic as compared to abomasum tissue extracts. CSF and plasma ghrelin levels were measured every 10 minutes over a 6 hours sampling period in 5 unanesthetised ovariectomised-estradiol implanted ewes. Mean CSF ghrelin concentrations were 1400-fold lower than circulating plasma levels. Cluster analysis indicated that CSF ghrelin levels were markedly pulsatile with a greater number of peaks than plasma ghrelin. Pulsatility parameters were closer for GH and CSF ghrelin than between GH and plasma ghrelin. Plasma ghrelin and GH levels were significantly correlated in three out of five ewes but CSF ghrelin and GH in one ewe only. Half of the CSF ghrelin episodes were preceded by a ghrelin peak in plasma with a 22 min delay. Cross-correlations between plasma GH and plasma or CSF ghrelin did not reach significance but a trend towards cross-correlation was observed from 20 to 0 min between plasma and CSF ghrelin. At 09h00, when food was returned to ewes, voluntary food intake did not elicit a consistent change in plasma or CSF ghrelin levels. In contrast, a peripheral ghrelin injection (1 mg, i.v.) immediately stimulated food intake, feeding behaviour, and GH secretion. These effects were concomitant with a more than ten-fold increase in plasma ghrelin levels while CSF ghrelin values only doubled 40 to 50 minutes after the injection. This suggests that peripherally-injected ghrelin crosses the blood brain barrier but only in low amount 2/29 and with relatively slow kinetics when compared to its effects on GH release and food intake. Taken together, these results support the notion that, in the ovariectomised-oestradiol implanted sheep model, peripheral ghrelin injection rapidly induces GH secretion, food intake and feeding behaviour, probably by acting on GHS-R1 receptors located in brain regions in which the blood brain barrier is not complete such as, for instance, the arcu...
