Albumin enhances negative feedback effect of cortisol on ACTH release from sheep pituitary cells

Albumin binds circulating glucocorticoids such as cortisol and consequently may modify the biological activity of these steroids by altering access to target cells. Because albumin is likely present in pituitary interstitial fluid, this study was designed to compare the negative feedback effect of cortisol on pituitary adrenocorticotropic hormone (ACTH) secretion from isolated sheep pituitary cells perifused with media containing 0.25% or 2% bovine serum albumin (BSA). Pituitary cells released less (P less than 0.05) immunoreactive ACTH in response to a 10-min treatment with 10 nM ovine corticotropin-releasing hormone (oCRH) after 45 min pretreatment with 0.5 microM cortisol when media contained 2% BSA vs. 0.25% BSA. A similar enhancement in negative feedback potency was observed when cells were treated with cortisol followed by 1 nM oCRH for 60 min, with an additional 10 min co-addition of arginine vasopressin. This potentiation was not observed when a noncortisol binding protein, ovalbumin, was substituted for BSA. However, the potentiating effect of albumin was present in perifused rat pituitary cells, indicating that the effect was not species specific. We conclude that albumin enhances the negative feedback potency of cortisol in anterior pituitary corticotrophs and that the process may operate under physiological conditions to enhance cell specific delivery of this steroid to appropriate targets.