Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness

Daniel M. Keenan, Ferdinand Roelfsema, Bernard J. Carroll, Ali Iranmanesh, Johannes D. Veldhuis

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Sex 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, body mass index (BMI) 18-32 kg/m2, previously studied at two medical centers. Plasma ACTH and cortisol concentrations were measured every 10 min for 24 h. The 145 sample pairs were used in each subject to estimate ACTH-cortisol drive via a logistic function. Statistical analyses revealed that 24-h 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 sex 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 sex 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 sex, 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.

Original languageEnglish (US)
Pages (from-to)R515-R523
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2
StatePublished - Aug 2009


  • Adrenal
  • Aging
  • Men
  • Secretion
  • Sex
  • Women

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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