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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/R515    most recent 00200.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Keenan, D. M. Articles by Veldhuis, J. D. PubMed PubMed Citation Articles by Keenan, D. M. Articles by Veldhuis, J. D.

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

¹Department of Statistics, University of Virginia, Charlottesville, Virginia; ²Department of Endocrinology and Metabolic Diseases; Leiden University Medical Center, The Netherlands; ³Pacific Behavioral Research Foundation, Carmel, California; ⁴Endocrine Service, Medical Section, Salem Veterans Affairs Medical Center, Salem, Virginia; and ⁵Endocrine Research Unit, Mayo Medical School, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota

Submitted 27 March 2009 ; accepted in final form 17 June 2009

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.

adrenal; aging; sex; men; women; secretion