This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Battaglia, D. F. Articles by Karsch, F. J. Search for Related Content PubMed PubMed Citation Articles by Battaglia, D. F. Articles by Karsch, F. J.

Systemic Challenge with Endotoxin Stimulates Corticotropin-Releasing Hormone and Arginine Vasopressin Secretion into Hypophyseal Portal Blood: Coincidence with Gonadotropin-Releasing Hormone Suppression¹

Departments of Physiology (D.F.B., F.J.K.) and Biology (L.A.T.), Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Dr. Fred J. Karsch, Reproductive Sciences Program, University of Michigan, 300 North Ingalls Building, Room 1101 SW, Ann Arbor, Michigan 48109-0404. E-mail: fjkarsch{at}umich.edu

We tested the hypothesis that systemic immune/inflammatory challenge (endotoxin) activates the neuroendocrine stress axis centrally by stimulating the secretion of CRH and arginine vasopressin (AVP) into hypophyseal portal blood. In addition, we examined the temporal association between this stimulation of the stress neuropeptides and the inhibition of pulsatile GnRH and LH secretion. Using alert, normally behaving ewes, hypophyseal portal and peripheral blood were sampled simultaneously at 10-min intervals for 14 h. Temperature was monitored remotely by telemetry at the same interval. Endotoxin (400 ng/kg, iv bolus) or saline as a control was injected after a 4-h baseline period. Portal blood was assayed for CRH, AVP, and GnRH, and peripheral blood was assayed for cortisol, progesterone, and LH. In controls, hypophyseal portal CRH and AVP remained just above or at assay sensitivity, and cortisol showed a regular rhythmic pattern unaffected by saline and typical of basal secretion. In contrast, endotoxin potently stimulated CRH and AVP secretion into portal blood, and cortisol and progesterone into peripheral blood. Both CRH and AVP generally rose and fell simultaneously, although the peak of the AVP response was approximately 10-fold greater than that of CRH. The AVP in portal blood was not due to recirculation of hormone secreted into the peripheral circulation by the posterior pituitary gland, because the AVP increase in peripheral blood was negligible relative to the marked increase in portal blood. The stimulation of CRH and AVP coincided with significant suppression of GnRH and LH pulsatile secretion in these same ewes and with the generation of fever. We conclude that endotoxin induces central activation of the neuroendocrine stress axis, stimulating both CRH and AVP release into the hypophyseal portal blood of conscious, normally behaving ewes. This response is temporally coupled to inhibition of pulsatile GnRH and LH release as well as with stimulation of adrenal cortisol and progesterone secretion and generation of fever.

This article has been cited by other articles:

				E. Xiao, L. Xia-Zhang, N. Vulliemoz, J. Rivier, and M. Ferin Astressin B, a Corticotropin-Releasing Hormone Receptor Antagonist, Accelerates the Return to Normal Luteal Function after an Inflammatory-Like Stress Challenge in the Rhesus Monkey Endocrinology, February 1, 2007; 148(2): 841 - 848. [Abstract] [Full Text] [PDF]

				C. Porcher, V. Sinniger, A. Juhem, P. Mouchet, and B. Bonaz Neuronal activity and CRF receptor gene transcription in the brains of rats with colitis Am J Physiol Gastrointest Liver Physiol, October 1, 2004; 287(4): G803 - G814. [Abstract] [Full Text] [PDF]

				K. M. Breen, C. A. Stackpole, I. J. Clarke, A. V. Pytiak, A. J. Tilbrook, E. R. Wagenmaker, E. A. Young, and F. J. Karsch Does the Type II Glucocorticoid Receptor Mediate Cortisol-Induced Suppression in Pituitary Responsiveness to Gonadotropin-Releasing Hormone? Endocrinology, June 1, 2004; 145(6): 2739 - 2746. [Abstract] [Full Text] [PDF]

				H. Watanobe and Y. Hayakawa Hypothalamic Interleukin-1{beta} and Tumor Necrosis Factor-{alpha}, But Not Interleukin-6, Mediate the Endotoxin-Induced Suppression of the Reproductive Axis in Rats Endocrinology, November 1, 2003; 144(11): 4868 - 4875. [Abstract] [Full Text] [PDF]

				A. Beishuizen and L. G. Thijs Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis Innate Immunity, February 1, 2003; 9(1): 3 - 24. [Abstract] [PDF]

				N. Debus, K. M. Breen, G. K. Barrell, H. J. Billings, M. Brown, E. A. Young, and F. J. Karsch Does Cortisol Mediate Endotoxin-Induced Inhibition of Pulsatile Luteinizing Hormone and Gonadotropin-Releasing Hormone Secretion? Endocrinology, October 1, 2002; 143(10): 3748 - 3758. [Abstract] [Full Text] [PDF]

				T. G. Harris, D. F. Battaglia, M. E. Brown, M. B. Brown, N. E. Carlson, C. Viguie, C. Y. Williams, and F. J. Karsch Prostaglandins Mediate the Endotoxin-Induced Suppression of Pulsatile Gonadotropin-Releasing Hormone and Luteinizing Hormone Secretion in the Ewe Endocrinology, March 1, 2000; 141(3): 1050 - 1058. [Abstract] [Full Text] [PDF]

				K. J. Suter, W. J. Song, T. L. Sampson, J.-P. Wuarin, J. T. Saunders, F. E. Dudek, and S. M. Moenter Genetic Targeting of Green Fluorescent Protein to Gonadotropin-Releasing Hormone Neurons: Characterization of Whole-Cell Electrophysiological Properties and Morphology Endocrinology, January 1, 2000; 141(1): 412 - 419. [Abstract] [Full Text] [PDF]