Submitted on April 6, 2009
Revised on June 17, 2009
Accepted on June 17, 2009
Gender Defines the Age Dependence of Endogenous ACTH-Cortisol Dose Responsiveness
Daniel M. Keenan1, Ferdinand Roelfsema2, Bernard J. Carroll, Ali Iranmanesh3, and Johannes D. Veldhuis4*
1 University of Virginia
2 Leiden University Medical Center
3 Salem Veterans Affairs Medical Center
4 Mayo School of Graduate Medical Education, Center for Translational Science Activities
* To whom correspondence should be addressed. E-mail: veldhuis.johannes{at}mayo.edu.
Gender influences adrenal glucocorticoid responses to ACTH in experimental animals. Whether similar sex differences operate in humans is unknown. To test this notion, we estimated ACTH-cortisol dose-response properties analytically in 48 healthy adults (N = 22 women, N = 26 men), ages 18 - 77 yr, BMI 18 - 32 kg/m2, previously studied at two medical centers. Plasma ACTH and cortisol concentrations were measured every 10 min for 24 hr. The 145 sample pairs were used in each subject to estimate ACTH-cortisol drive via a logistic function. Statistical analyses revealed that 24-hr cortisol secretion (> 82% pulsatile) fell in men (r = -0.38, P = 0.028) and rose in women (r = +0.37, P = 0.045) with age (P = 0.01 gender effect). The mechanisms involved decreased ACTH efficacy with age in men (r = -0.35, P = 0.04), and increased ACTH efficacy with age in women (r = +0.42, P = 0.025) [P = 0.009 gender effect]. ACTH potency diminished with higher BMI in men (r = +0.38, P = 0.029) and in the cohort as a whole (r = 0.34, P = 0.0085). These outcomes demonstrate that gender, age and BMI modulate selective properties of endogenous ACTH-cortisol drive in humans, thereby indicating the need to control these three major variables in experimental comparisons.
