Responsiveness of isolated adrenocortical cells from lean and obese Zucker rats to ACTH

Abstract

Morning plasma corticosterone concentrations have been reported to be elevated in obese Zucker rats compared with lean rats. The aim of this study was to determine if differences in adrenal sensitivity or maximal responsiveness to adrenocorticotropic hormone (ACTH)-(1-24) could account for this disparity. Serum and adrenal glands were collected from lean and obese, male and female Zucker rats (10-13 wk old) between 10:00 and 11:00 A.M. Adrenocortical cells were isolated and challenged with ACTH-(1-24). The serum corticosterone and ACTH concentrations were significantly greater in obese males compared with lean males (45.3 +/- 10.3 vs. 23.2 +/- 1.45 ng/ml and 156.6 +/- 15.3 vs. 113.3 +/- 9.4 pg/ml, respectively). Although serum corticosterone concentrations were similar in female rats, serum ACTH concentrations tended (P = 0.07) to be lower in obese female rats than in lean female rats (67.6 +/- 9.3 vs. 103.5 +/- 15.1 pg/ml, respectively). The median effective concentration (EC50) and the maximal corticosterone response per microgram of DNA of dose-response curves derived from lean and obese rats were not significantly different. Additionally, a morphometric evaluation of adrenal tissue from lean and obese rats suggested that cells of the zona glomerulosa were smaller in obese rats than in lean rats. Our data confirm that morning serum corticosterone concentrations are elevated in 10- to 13-wk-old male Zucker rats. This difference does not appear to be due to differences in the sensitivity or maximal secreting capacity of adrenocortical cells to ACTH.