Biological actions of cholecystokinin

The use of pigs in neuroscience: modeling brain disorders.

Vocalization of farm animals as a measure of welfare

The hypothalamo-neurohypophysial system (HNS) is the major peptidergic neurosecretory system through which the brain controls peripheral physiology. The hormones vasopressin and oxytocin released from the HNS at the neurohypophysis serve homeostatic functions of water balance and reproduction. From a physiological viewpoint, the core question on the HNS has always been, "How is the rate of hormone production controlled?" Despite a clear description of the physiology, anatomy, cell biology, and biochemistry of the HNS gained over the last 100 years, this question has remained largely unanswered. However, recently, significant progress has been made through studies of gene identity and gene expression in the magnocellular neurons (MCNs) that constitute the HNS. These are keys to mechanisms and events that exist in the HNS. This review is an inventory of what we know about genes expressed in the HNS, about the regulation of their expression in response to physiological stimuli, and about their function. Genes relevant to the central question include receptors and signal transduction components that receive and process the message that the organism is in demand of a neurohypophysial hormone. The key players in gene regulatory events, the transcription factors, deserve special attention. They do not only control rates of hormone production at the level of the gene, but also determine the molecular make-up of the cell essential for appropriate development and physiological functioning. Finally, the HNS neurons are equipped with a machinery to produce and secrete hormones in a regulated manner. With the availability of several gene transfer approaches applicable to the HNS, it is anticipated that new insights will be obtained on how the HNS is able to respond to the physiological demands for its hormones.

Gene regulation in the magnocellular hypothalamo-neurohypophysial system.

Endotoxin is considered to be a systemic (immunological) stressor eliciting a prolonged activation of the hypothalamo-pituitary-adrenal (HPA) axis. The HPA-axis response after an endotoxin challenge is mainly due to released cytokines (IL-1, IL-6 and TNF-alpha) from stimulated peripheral immune cells, which in turn stimulate different levels of the HPA axis. Controversy exists regarding the main locus of action of endotoxin on glucocorticoid secretion, since the effect of endotoxin on this neuro-endocrine axis has been observed in intact animals and after ablation of the hypothalamus; however, a lack of LPS effect has been described at both pituitary and adrenocortical levels. The resulting increase in adrenal glucocorticoids has well-documented inhibitory effects on the inflammatory process and on inflammatory cytokine release. Therefore, immune activation of the adrenal gland by endotoxin is thought to occur by cytokine stimulation of corticosteroid-releasing hormone (CRH) production in the median eminence of the hypothalamus, which, in turn stimulates the secretion of ACTH from the pituitary. Acute administration of endotoxin stimulates ACTH and cortisol secretion and the release of CRH and vasopressin (AVP) in the hypophysial portal blood. During repeated endotoxemia, tolerance of both immune and HPA function develops, with a crucial role for glucocorticoids in the modulation of the HPA axis. A single exposure to a high dose of LPS can induce a long-lasting state of tolerance to a second exposure of LPS, affecting the response of plasma TNF-alpha and HPA hormones. Although there are gender differences in the HPA response to endotoxin and IL-1, these responses are enhanced by castration and attenuated by androgen and estrogen replacement. Estrogens attenuate the endotoxin-induced stimulation of IL-6, TNF-alpha and IL-1ra release and subsequent activation in postmenopausal women. There appears to be a temporal and functional relation between the HPA-axis response to endotoxin and nitric oxide formation in the neuro-endocrine hypothalamus, suggesting a stimulatory role for nitric oxide in modulating the HPA response to immune challenges.

Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis.

Restraint, but not frustration, induces prostaglandin-mediated hyperthermia in pigs

Heart rate and stress hormone responses of sheep to road transport following two different loading procedures

Prepubertal pigs (n = 8) treated with bacterial endotoxin (20 micrograms lipopolysaccharide; LPS) exhibited a sustained (4 h) hyperthermia, increased plasma concentrations of cortisol, prolactin, growth hormone and vasopressin, but no change in adrenaline or noradrenaline levels was observed. All these effects were prevented or attenuated when the animals were pretreated intravenously with the cyclo-oxygenase inhibitor indomethacin (IND; 2 mg/kg). Similarly, in pigs (n = 3 per treatment) given IND, LPS or IND + LPS, parallel changes in the neuronal expression of c-Fos were observed in hypothalamic regions concerned with thermoregulation, neurohypophysial secretion, and the control of pituitary-adrenocortical function. The stimulatory action of LPS in the median preoptic, supraoptic and paraventricular nuclei was prevented by IND, whereas IND given alone was without effect. These findings suggest that inducible cyclo-oxygenase pathways are responsible for the febrile and neuroendocrine effects of endotoxin in this species.

Cyclo-oxygenase mediation of endotoxin-induced fever, anterior and posterior pituitary hormone release, and hypothalamic c-Fos expression in the prepubertal pig.

Hyperthermia-associated changes in Fos protein in the median preoptic and other hypothalamic nuclei of the pig following intravenous administration of prostaglandin E2

R.F Parrott

Papers

Restraint, but not frustration, induces prostaglandin-mediated hyperthermia in pigs

Heart rate and stress hormone responses of sheep to road transport following two different loading procedures

Cyclo-oxygenase mediation of endotoxin-induced fever, anterior and posterior pituitary hormone release, and hypothalamic c-Fos expression in the prepubertal pig.

Hyperthermia-associated changes in Fos protein in the median preoptic and other hypothalamic nuclei of the pig following intravenous administration of prostaglandin E2

Effects of the 5-HT1A receptor agonist 8-OH-DPAT on operant food intake in food-deprived pigs.