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We previously reported that centrally-induced sympathetic activation in response to cold stress is associated with a polycystic ovarian condition in rats, and thyrotrophin-releasing hormone (TRH) released locally from the magnocellular region of the paraventricular nucleus (PVN) appears to be involved in this activation. Because TRH neurones express NMDA glutamate receptors, in the present study, we investigated the role of glutamate in the increased release of TRH from magnocellular neurones induced by cold stress and its relationship to ovarian neurotransmission. Animals with a push–pull cannula stereotaxically implanted into the magnocellular portion of the PVN were exposed to cold stress (4 °C for 64 h) and subjected to intracerebral perfusion. Perfusate fractions were obtained and analysed by high-performance liquid chromatography to measure glutamate and GABA levels. Glutamate, but not GABA, release increased significantly in animals perfused under cold exposure. In vivo administration of glutamate to the PVN increased TRH release. Injection of MK-801 into the magnocellular portion of the PVN reduced ovarian noradrenaline turnover and led to an increase in catecholamine concentration from the adrenal glands and celiac ganglia. Taken together, the results obtained in the present study strongly suggest that glutamate release from the magnocellular PVN is sensitive to cold stress and that glutamate acts through the NMDA receptor to mediate cold-induced TRH release. This in turn triggers hypothalamic-ovarian pathway activation, which might be responsible for the polycystic condition induced by cold stress and other ovarian pathologies characterised by increased sympathetic discharge. [ABSTRACT FROM AUTHOR]

As in other species, exogenous administration of ghrelin, an endogenous ligand for the growth hormone (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 the present study, cerebrospinal fluid (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 compared to abomasum tissue extracts. 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 09.00 h, when food was returned to ewes, voluntary food intake did not elicit a consistent change in plasma or CSF ghrelin levels. By contrast, a peripheral ghrelin injection (1 mg, i.v.) immediately stimulated feeding behaviour and GH secretion. These effects were concomitant with a more than ten-fold increase in plasma ghrelin levels, whereas CSF ghrelin values only doubled 40–50 min after the injection. This suggests that peripherally-injected ghrelin crosses the blood–brain barrier, but only in low amount and with relatively slow kinetics compared to its effects on GH release and food intake. Taken together, the results obtained in the present study support the notion that, in the ovariectomised-oestradiol implanted sheep model, peripheral ghrelin injection rapidly induces GH secretion, and feeding behaviour, probably by acting on growth hormone secretagogue receptor subtype 1 located in brain regions in which the blood–brain barrier is not complete (e.g. the arcuate nucleus). [ABSTRACT FROM AUTHOR]

Recent studies suggest thyrotrophin-releasing hormone (TRH) serves as a neurotransmitter and thereby provides a functional vegetative connection between the brain and the ovary. In the present study, magnocellular neurones of the paraventricular nucleus (PVN) in animals subjected to cold exposure were studied to determine the hypothalamic origin of the TRH involved in this pathway. In situ hybridisation analysis of hypothalamic tissue showed that cold exposure causes a two-fold increase in the total number of neurones expressing TRH mRNA in the PVN. Immunohistochemical studies showed that TRH peptide is localised to the magnocellular PVN and that the number of TRH immunoreactive cells increases two-fold following 64 h of cold exposure. Double-immunostaining for MAP-2 and TRH revealed that TRH peptide is localised in the perikarya of the magnocellular neurones. TRH release was measured in vivo from the magnocellular portion of the PVN using push–pull perfusion. Although controls exhibited a very low level of TRH release, animals subjected to cold showed a pulsatile-like TRH release profile with two different patterns of release: (i) low basal level with small bursts of TRH release and (ii) a profile with an up to seven-fold increase in TRH release compared to controls. The colocalisation of TRH with the specific somato-dendritic marker MAP-2 in processes of the magnocellular neurones suggested a local release of TRH. Additional studies demonstrated a reduction in ovarian noradrenaline content after 48 h of cold exposure, a feature indicative of nerve activation at the terminal organ. After 64 h of cold exposure, the ovarian noradrenaline returned to control values but the noradrenaline content of the coeliac ganglia was increased, suggesting a compensatory effect originating in the cell bodies of the sympathetic neurones that innervate the ovary. The correlation between the local release of TRH from dendrites within the magnocellular PVN in conditions of cold and the activation of the sympathetic nerves supplying the ovary raises the possibility that TRH contributes to the processing regulating sympathetic outflow and may thereby impact on the functional activity of the ovary. [ABSTRACT FROM AUTHOR]

Both growth hormone (GH)/insulin growth factor (IGF)-1 axis and energy balance have been implicated in longevity independently. The aim of the present study was to characterize the effect of a 72-h fasting period at 3 months of age in four different rat strains: (i) Wistar and (ii) Fischer 344 rats, which develop obesity with age, and (iii) Brown Norway and (iv) Lou C rats, which do not. Wistar rats ate more, were significantly bigger, and presented with higher plasma leptin and lower ghrelin levels and hypothalamic growth hormone-releasing hormone (GHRH) content than rats from the three other strains. Plasma insulin and IGF-1 levels were lower in Brown Norway and Lou C rats, and somatostatin content was lower in Brown Norway rats only. Glycaemia was lower in Lou C rats that displayed a lower relative food intake compared to Fischer and Wistar rats. Brown Norway rats showed a greater caloric efficiency than the three other strains. Concerning major hypothalamic neuropeptides implicated in feeding, similar amounts were detected in the four strains for neuropeptide Y, agouti-related peptide, galanin, melanin-concentrating hormone,α-melanocortin-stimulating hormone (α-MSH) and corticotropin-releasing hormone. Orexin A appeared to be slightly elevated in Fischer rats and cocaine amphetamine-regulated transcript (CART)55−102 diminished in Brown Norway. At the mRNA level, orexin A, GHSR1,α-MSH and CART expression were higher in Wistar and Lou C rats. Principal component analysis confirmed the presence of two main factors in thead libitumrat population; the first being associated with growth-related parameters and the second being associated with food intake regulation. Hypothalamic GHRH and somatostatin content were positively correlated with feeding-related neuropeptides such asα-MSH for GHRH, and orexin A and CART for both peptides. Plasma ghrelin levels were negatively correlated with leptin and IGF-1 levels. Finally, a 72-h fasting period affected minimally body weight, plasma IGF-1 and leptin levels in Lou C rats compared to the three other strains, and plasma insulin levels were less affected in Brown Norway rats. In conclusion, Wistar shorter life span is consistent with its already fatter phenotype at 3 months of age. In terms of IGF-1, glycaemia and leptin responses to fasting, the Lou strain, which presents with a low food intake/body weight and caloric efficiency, is the least affected. The link between food intake regulation, GH axis and ageing is further demonstrated by principal component analysis, where GHRH and somatostatin were found to be strongly associated with energy homeostasis parameters. [ABSTRACT FROM AUTHOR]