Paradoxical responses of hypothalamic corticotropin-releasing factor (CRF) messenger ribonucleic acid (mRNA) and CRF-41 peptide and adenohypophysial proopiomelanocortin mRNA during chronic inflammatory stress.

Abstract

We have determined the time course of the neuroendocrine response of Piebald-Viral-Glaxo (PVG) rats during the development of mycobacterially induced adjuvant arthritis. Anterior pituitary POMC mRNA increased at the time of onset of mycobacterially induced arthritis, but, paradoxically, coincident with the first signs of arthritis there was a consistent fall in CRF mRNA in the hypothalamic paraventricular nucleus. Coincident with this fall in CRF message, there was a corresponding decrease in CRF-41 peptide release into the hypophysial portal blood (HPB). In contrast, however, vasopressin release into the HPB was increased. There was an increase in adrenal weight associated with the development of arthritis, reflecting chronic activation of the HPA axis, which was reflected by increased circulating corticosterone concentrations. The synthetic adjuvant CP20961, which has different antigenic determinants, also caused an increase in POMC mRNA in the anterior pituitary, a decrease in CRF mRNA in the hypothalamic paraventricular nucleus, and a decrease in CRF-41 peptide release into the HPB in PVG rats 28 days after the induction of the arthritis. The arginine vasopressin level was not significantly different from the control value. In Sprague-Dawley rats, mycobacterial adjuvant resulted in a similar increase in POMC mRNA in the anterior pituitary 28 days after injection of the adjuvant. In this strain of rat there was no corresponding change in CRF mRNA. While there are some strain differences in the degree of change in CRF mRNA, both strains showed a common paradox of a marked increase in adenohypophyseal POMC mRNA not associated with increased CRF mRNA or peptide release. In the PVG strain of rat, CRF actually appears to be inhibited. The mechanisms involved in this disparity are unclear.

Early-life exposure to endotoxin alters hypothalamic–pituitary–adrenal function and predisposition to inflammation

“…5) (4, 13). Although CRH and AVP mRNA generally both increase in response to acute stress, PVN CRH mRNA levels decrease and AVP mRNA levels increase in response to chronic inf lammation associated with AA (23)(24)(25)(26). In our current studies, we observed similar increments in PVN AVP mRNA and decrements in CRH mRNA in SALINE, ENDO, and HANDLED animals (Fig.…”

Human and murine pituitary expression of leukemia inhibitory factor. Novel intrapituitary regulation of adrenocorticotropin hormone synthesis and secretion.

“…Pituitary cytokine interactions may occur independently of CRH (62), and autocrine or paracrine modulation of ACTH secretion independent of changes in CRH may also occur during systemic stress (63). Nevertheless, the factors controlling LIF expression and action within the pituitary are not yet known.…”

Neurobiology of the stress response early in life: evolution of a concept and the role of corticotropin releasing hormone

“…55 Thus, in the mature rat, repeated variable-or immobilization-stress has been shown to increase CRH mRNA expression in PVN, [55][56][57] whereas chronic inflammatory stress has been shown to decrease CRH mRNA levels in this nucleus. 58 A potential basis for the varying effects of specific recurrent or chronic stressors on CRH synthesis may derive from the qualitative differences of each stressor (eg, physical and psychological components). 59 In the immature rat, the effect of a single acute stress on CRH mRNA expression in PVN differs from that of recurrent stress.…”