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Title:   Author  item
                                            ADCOCK, REBECCA - UNIVERSITY OF TENNESSEEitem
                                            KATTESH, HENRY - UNIVERSITY OF TENNESSEEitem
                                            ROBERTS, MARY - UNIVERSITY OF TENNESSEEitem
                                            Carroll, Jeffery

                                                         - *Jeff Carroll*item
                                            SAXTON, ARNOLD - UNIVERSITY OF TENNESSEE
  Submitted to: Stress: The International Journal on Biology of Stress
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/10/2007
                                    Publication  Date: 8/1/2007
                                    Citation: Adcock, R., Kattesh, H., Roberts, M., Carroll, J.A., Saxton, A. 2007. Temporal relationships between plasma cortisol, corticosteriod-binding globulin (CBG), and the free cortisol index (FCI) in pigs in response to adrenal stimulation or suppression. Stress: The International Journal on Biology of Stress. 10(3):305-310.Interpretive Summary: The active form of cortisol within the circulation is considered to be that which is free, or unbound, and that which is loosely bound to albumin, thus allowing it to be biologically available to the cell. The majority of circulating cortisol in humans and swine is bound to its specific carrier glycoprotein, corticosteroid-binding globulin (CBG), where it not only transports, but also modulates cortisol availability within the circulation. In swine, more than 60% of cortisol in circulation is bound to porcine corticosteroid-binding globulin (pCBG), and is considered biologically inactive. Limitations exist when only total plasma cortisol levels are used to assess the stress response in swine in situations where pCBG changes significantly. The Free Cortisol Index (FCI), which is the ratio of total cortisol to CBG, has been shown to be a suitable estimate of the unbound or free fraction of cortisol in plasma. The objective of this study was to document the changes in plasma total cortisol, pCBG, and FCI in pigs over a 6-h period in response to adrenal stimulation or suppression. The results from this study demonstrate that by using pCBG measurement and the calculation of FCI, a more complete interpretation of the biological significance of fluctuating plasma cortisol levels in swine can be made. The significance of the observed plasma cortisol-CBG relationship reported here may reside in the calculation of the FCI. The FCI increased following adrenal stimulation, resulting from an increase in total cortisol and a decrease in pCBG concentrations. In the adrenal suppression group, the FCI decreased as a result of a suppression of total cortisol and an increase in pCBG. An increase in CBG synthesis corresponding with decreased cortisol levels may increase cortisol conservation by binding as much cortisol as possible. Since approximately 60% of total cortisol in circulation is bound to pCBG in the pig, the amount of cortisol that is available to cells may be misrepresented if the concentration of pCBG is not taken into consideration along with that of total cortisol. The FCI can provide a better understanding of assessing temporal changes in the adrenal response in animals than by measuring total plasma cortisol alone.
                                Technical Abstract: In swine, more than 60% of cortisol in circulation is bound to its carrier glycoprotein, porcine corticosteroid-binding globulin (pCBG), and is considered biologically inactive. Limitations exist when only total plasma cortisol levels are used to assess the stress response in swine in situations where pCBG changes significantly. The Free Cortisol Index (FCI), which is the ratio of total cortisol to CBG, has been shown to be a suitable estimate of the unbound, or free fraction, of cortisol in plasma. The objective of this study was to document the changes in plasma total cortisol, pCBG, and FCI in pigs over a 6-h period in response to adrenal stimulation or suppression. Twenty-four 8-wk old pigs, allotted in equal numbers, were administered ACTH, dexamethasone, or saline, and blood samples collected every 15 min over a 6 h period. In pigs treated with ACTH, the FCI increased (P < 0.001) in a fashion similar to that of total cortisol, while pCBG values remained stable. In dexamethasone treated pigs, both FCI and total cortisol decreased (P < 0.001) with a subsequent elevation in pCBG concentrations. An inverse relationship (P < 0.05) was observed between plasma cortisol and pCBG for saline (r = -0.36) and dexamethasone (r = -0.19) treated pigs for all samples collected following treatment administration. Plasma cortisol and pCBG values for ACTH treated pigs changed in a direct linear manner (r = 0.27; P = 0.007) in samples collected from 0.25 to 3.0 h. This study demonstrates that by using pCBG measurement and the calculation of FCI, a more complete interpretation of the biological significance of fluctuating plasma cortisol levels in swine can be made.


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