Effect of endotoxin on the hypothalamic-pituitary-adrenal axis in sheep

Abstract

Endotoxin has been shown to stimulate ACTH and cortisol secretion through an action at the hypothalamic level. However, the nature of hypothalamic neurohormones, corticotropin-releasing hormone (CRH) and especially arginine vasopressin (AVP), involved in that regulation is still controversial. The purpose of this study was to determine the effects of an acute i.v. endotoxin administration on CRH and AVP secretion into hypophysial portal blood (HPB). The experiment has been performed in sheep since it is possible to collect HPB and quantify CRH and AVP secretion in this animal under physiological conditions. The release of both peptides into HPB was stimulated by endotoxin injection, the increase in portal AVP being more pronounced than that of CRH. An initial, transient, increase in jugular AVP concentrations was observed, probably due to the activation of magnocellular AVP neurons. In conclusion, our data indicate that the activation of the pituitaryadrenal axis after endotoxin injection is associated with an increased release of both CRH and AVP into HPB. Magnocellular AVP neurons are initially stimulated while parvocellular CRH and AVP neurons are stimulated throughout the experiment.

No Alteration in Serum Leptin Levels during Acute Endotoxemia in Sheep.

“…3). The rapid rise of plasma glucocorticoids after LPS administration is quite consistent with the previously reported results not only in rodents but also in live-stock animals including sheep [3,4]. Since serum ACTH level is also increased after LPS injection [3], the increased cortisol would be due, at least in part, to adrenocortical activation.…”

The effect of repeated endotoxin injections on gonadotropin secretion in ewes

“…It is held that inflammatory-dependent HPA axis activation plays an important role in the inhibition of reproduction, especially affecting LH release (Coleman et al, 1993;Debus et al, 2002). Immune stress stimulates not only cortisol release, but also other HPA axis components, increases the synthesis and release of arginine vasopressin and corticotropin-releasing hormone in the hypothalamus, stimulates secretion of adrenocorticotrophic hormone from the pituitary and corticosterone or cortisone from the adrenal cortex (Dadoun et al, 1998;Melmed, 2001). All of them exhibit inhibitory proprieties in relation to the HPG axis (Battaglia et al, 1998;Dobson et al, 2003;Maeda and Tsukamura, 2006).…”

Immune stress up regulates <i>TLR4</i> and <i>Tollip</i> gene expression in the hypothalamus of ewes

“…A study performed on sheep showed that peripheral immune challenge induced by LPS injection leads to elevation of the plasma cortisol level in sheep (Coleman et al, 1993). Immune stress stimulates not only the release of cortisol, but also of other HPA axis components, increases the synthesis and release of AVP and corticotropin-releasing factor (CRF) in the hypothalamus, stimulates secretion of ACTH from the pituitary and of corticosterone or cortisone from the adrenal cortex (Dadoun et al, 1998;Melmed, 2001). The activation of the stress axis may directly affect the level of TLR4 gene expression in the hypothalamus.…”

“…Some sickness symptoms, however, could be the result of hypothalamic-pituitary-adrenal axis (HPA axis) activation. Endotoxin is known as a profound stressor (Dadoun et al, 1998). It was previously reported that peripheral administration of LPS stimulates cortisol release in a variety of animal species, including sheep (Coleman et al, 1993).…”