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Title:   Author  item
                                            ADCOCK, REBECCA - UNIVERSITY OF TENNESSEEitem
                                            KATTESH, HENRY - UNIVERSITY OF TENNESSEEitem
                                            ROBERTS, MARY - UNIVERSITY OF TENNESSEEitem
                                            SEXTON, ARNOLD - UNIVERSITY OF TENNESSEEitem
                                            Carroll, Jeffery

                                                         - *Jeff Carroll*
  Submitted to: Journal of Animal and Veterinary Advances
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 11/16/2005
                                    Publication  Date: 12/12/2005
                                    Citation: Adcock, R.J., Kattesh, H.G., Roberts, M.P., Saxton, A.M., Carroll, J.A. 2006. Relationships between plasma cortisol, corticosteroid-binding globulin (CBG) and the free cortisol index (FCI) in pigs over a 24 h period. Journal of Animal and Veterinary Advances. 5(1):85-91.Interpretive Summary: A circadian pattern of total cortisol is present in many species including man, horse, and pig. For the pig, this rhythm is characterized by peak amounts of circulating cortisol secreted in the morning with reduced levels during the afternoon and early evening. Cortisol exists in the bloodstream in biologically active and inactive forms. The active form consists of cortisol that 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 is tightly bound to its specific carrier glycoprotein, corticosteroid-binding globulin (CBG). The percentage of CBG-bound cortisol in circulation varies among species from 65% for swine to more than 90% for humans. A diurnal rhythm for CBG has been reported in both humans and rats. In humans, CBG binding capacity for cortisol paralleled oscillations for the diurnal rhythm of total cortisol with a lag time of approximately four hours. No lag time between oscillations of corticosterone and CBG have been observed in the circadian pattern of CBG in rats. During stressful situations, cortisol levels can increase while CBG levels may increase or decrease, leaving the free cortisol fractions to be inadequately represented. The free cortisol index (FCI), a ratio of circulating total plasma cortisol to CBG, has been demonstrated in human studies to be a reliable and easy to use measure of plasma free cortisol. The objectives of this study were to examine the relationship between the FCI and actual levels of circulating free cortisol over a 24 h period and to document changes in plasma total cortisol, percent free cortisol, free cortisol, porcine CBG (pCBG) and FCI in response to adrenal stimulation in pigs. The relationship between plasma free cortisol and the free cortisol index (FCI, the ratio of cortisol to CBG) was evaluated in eight 8-wk old pigs over a 24 h period and in response to administration of saline or ACTH. A high (P < 0.001) correlation was found between actual free cortisol and the FCI in both saline (r = 0.73) and ACTH (r = 0.85) treated pigs. A diurnal rhythm was apparent for total cortisol, free cortisol, percent free cortisol, pCBG, and the FCI. Total cortisol (P < 0.05), free cortisol (P < 0.05), and the FCI (P < 0.01) were elevated during the first four hours following administration of ACTH. Concentrations of pCBG differed (P < 0.001) over time and were higher (P < 0.01) for ACTH treated pigs over the 24 h period. The results from this study affirm the contention that FCI is a suitable estimate of free cortisol in swine. To our knowledge, this is the first experiment to measure plasma total cortisol, pCBG, percent cortisol, plasma free cortisol, and FCI over a 24 h period. It is also the first experiment to indicate the relationship between plasma cortisol and pCBG in swine immediately following acute stimulation or suppression of the adrenal gland. By factoring in CBG values through the application of the FCI, a more accurate portrayal of the availability of circulating cortisol is possible. The calculation of the FCI illustrates the amount of free cortisol available to cells without employing timeconsuming and expensive analytical procedures for the actual measure of free cortisol.
                                Technical Abstract: The relationship between plasma free cortisol and the free cortisol index (FCI, the ratio of cortisol to CBG) was evaluated in eight 8-wk old pigs over a 24 h period and in response to administration of saline or ACTH. A high (P < 0.001) correlation was found between actual free cortisol and the FCI in both saline (r = 0.73) and ACTH (r = 0.85) treated pigs. A diurnal rhythm was apparent for total cortisol, free cortisol, percent free cortisol, pCBG, and the FCI. Total cortisol (P < 0.05), free cortisol (P < 0.05), and the FCI (P < 0.01) were elevated during the first four hours following administration of ACTH. Concentrations of pCBG differed (P < 0.001) over time and were higher (P < 0.01) for ACTH treated pigs over the 24 h period. The results from this study affirm the contention that FCI is a suitable estimate of free cortisol in swine.


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