Gender determines ACTH recovery from hypercortisolemia in healthy older humans

Animesh Sharma, Paul Aoun, Jean Wigham, Sue Weist, Johannes D Veldhuis

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective Available clinical data raise the possibility that stress-adaptive mechanisms differ by gender. However, this notion has not been rigorously tested in relation to cortisol-mediated negative feedback. Materials/Methods Degree of ACTH inhibition during and recovery from an experimental cortisol clamp was tested in 20 healthy older subjects (age 60 ± 2.2 y). Volunteers received oral placebo or ketoconazole (KTCZ) to inhibit adrenal steroidogenesis along with i.v. infusions of saline or a low vs high physiological dose of cortisol in a prospectively randomized double-blind, placebo-controlled design. ACTH and cortisol concentrations were measured every 10 min during the feedback-clamp phase and thereafter (recovery or escape phase). Corticosteroid-binding globulin (CBG) was measured, and free cortisol concentrations were calculated. Results Gender did not determine mean ACTH concentrations during the saline or cortisol feedback-clamp phases per se. However, women had markedly impaired ACTH recovery after stopping both low- and high-dose cortisol infusions compared with men (P = 0.005, KTCZ/low-dose cortisol arm; and P = 0.006, KTCZ/high-dose cortisol arm). Decreased ACTH recovery in women was accompanied by lower total and free cortisol concentrations, pointing to heightened feedback inhibition of hypothalamo-pituitary drive of ACTH secretion as the main mechanism. Conclusions In summary, gender or a factor related to gender, such as sex steroids or body composition, determines recovery of ACTH secretion from cortisol-enforced negative feedback. Attenuated ACTH recovery in post-menopausal women may have relevance to sex differences in stress-related adaptations.

Original languageEnglish (US)
Pages (from-to)1819-1829
Number of pages11
JournalMetabolism: Clinical and Experimental
Volume62
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Adrenocorticotropic Hormone
Hydrocortisone
Ketoconazole
Placebos
Transcortin
Body Composition
Sex Characteristics
Volunteers
Healthy Volunteers
Steroids

Keywords

  • Aging
  • Cortisol
  • Feedback
  • Human

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Gender determines ACTH recovery from hypercortisolemia in healthy older humans. / Sharma, Animesh; Aoun, Paul; Wigham, Jean; Weist, Sue; Veldhuis, Johannes D.

In: Metabolism: Clinical and Experimental, Vol. 62, No. 12, 12.2013, p. 1819-1829.

Research output: Contribution to journalArticle

Sharma, Animesh ; Aoun, Paul ; Wigham, Jean ; Weist, Sue ; Veldhuis, Johannes D. / Gender determines ACTH recovery from hypercortisolemia in healthy older humans. In: Metabolism: Clinical and Experimental. 2013 ; Vol. 62, No. 12. pp. 1819-1829.
@article{6298b7ac86ed49449aa9d40c59c9f829,
title = "Gender determines ACTH recovery from hypercortisolemia in healthy older humans",
abstract = "Objective Available clinical data raise the possibility that stress-adaptive mechanisms differ by gender. However, this notion has not been rigorously tested in relation to cortisol-mediated negative feedback. Materials/Methods Degree of ACTH inhibition during and recovery from an experimental cortisol clamp was tested in 20 healthy older subjects (age 60 ± 2.2 y). Volunteers received oral placebo or ketoconazole (KTCZ) to inhibit adrenal steroidogenesis along with i.v. infusions of saline or a low vs high physiological dose of cortisol in a prospectively randomized double-blind, placebo-controlled design. ACTH and cortisol concentrations were measured every 10 min during the feedback-clamp phase and thereafter (recovery or escape phase). Corticosteroid-binding globulin (CBG) was measured, and free cortisol concentrations were calculated. Results Gender did not determine mean ACTH concentrations during the saline or cortisol feedback-clamp phases per se. However, women had markedly impaired ACTH recovery after stopping both low- and high-dose cortisol infusions compared with men (P = 0.005, KTCZ/low-dose cortisol arm; and P = 0.006, KTCZ/high-dose cortisol arm). Decreased ACTH recovery in women was accompanied by lower total and free cortisol concentrations, pointing to heightened feedback inhibition of hypothalamo-pituitary drive of ACTH secretion as the main mechanism. Conclusions In summary, gender or a factor related to gender, such as sex steroids or body composition, determines recovery of ACTH secretion from cortisol-enforced negative feedback. Attenuated ACTH recovery in post-menopausal women may have relevance to sex differences in stress-related adaptations.",
keywords = "Aging, Cortisol, Feedback, Human",
author = "Animesh Sharma and Paul Aoun and Jean Wigham and Sue Weist and Veldhuis, {Johannes D}",
year = "2013",
month = "12",
doi = "10.1016/j.metabol.2013.08.014",
language = "English (US)",
volume = "62",
pages = "1819--1829",
journal = "Metabolism: Clinical and Experimental",
issn = "0026-0495",
publisher = "W.B. Saunders Ltd",
number = "12",

}

TY - JOUR

T1 - Gender determines ACTH recovery from hypercortisolemia in healthy older humans

AU - Sharma, Animesh

AU - Aoun, Paul

AU - Wigham, Jean

AU - Weist, Sue

AU - Veldhuis, Johannes D

PY - 2013/12

Y1 - 2013/12

N2 - Objective Available clinical data raise the possibility that stress-adaptive mechanisms differ by gender. However, this notion has not been rigorously tested in relation to cortisol-mediated negative feedback. Materials/Methods Degree of ACTH inhibition during and recovery from an experimental cortisol clamp was tested in 20 healthy older subjects (age 60 ± 2.2 y). Volunteers received oral placebo or ketoconazole (KTCZ) to inhibit adrenal steroidogenesis along with i.v. infusions of saline or a low vs high physiological dose of cortisol in a prospectively randomized double-blind, placebo-controlled design. ACTH and cortisol concentrations were measured every 10 min during the feedback-clamp phase and thereafter (recovery or escape phase). Corticosteroid-binding globulin (CBG) was measured, and free cortisol concentrations were calculated. Results Gender did not determine mean ACTH concentrations during the saline or cortisol feedback-clamp phases per se. However, women had markedly impaired ACTH recovery after stopping both low- and high-dose cortisol infusions compared with men (P = 0.005, KTCZ/low-dose cortisol arm; and P = 0.006, KTCZ/high-dose cortisol arm). Decreased ACTH recovery in women was accompanied by lower total and free cortisol concentrations, pointing to heightened feedback inhibition of hypothalamo-pituitary drive of ACTH secretion as the main mechanism. Conclusions In summary, gender or a factor related to gender, such as sex steroids or body composition, determines recovery of ACTH secretion from cortisol-enforced negative feedback. Attenuated ACTH recovery in post-menopausal women may have relevance to sex differences in stress-related adaptations.

AB - Objective Available clinical data raise the possibility that stress-adaptive mechanisms differ by gender. However, this notion has not been rigorously tested in relation to cortisol-mediated negative feedback. Materials/Methods Degree of ACTH inhibition during and recovery from an experimental cortisol clamp was tested in 20 healthy older subjects (age 60 ± 2.2 y). Volunteers received oral placebo or ketoconazole (KTCZ) to inhibit adrenal steroidogenesis along with i.v. infusions of saline or a low vs high physiological dose of cortisol in a prospectively randomized double-blind, placebo-controlled design. ACTH and cortisol concentrations were measured every 10 min during the feedback-clamp phase and thereafter (recovery or escape phase). Corticosteroid-binding globulin (CBG) was measured, and free cortisol concentrations were calculated. Results Gender did not determine mean ACTH concentrations during the saline or cortisol feedback-clamp phases per se. However, women had markedly impaired ACTH recovery after stopping both low- and high-dose cortisol infusions compared with men (P = 0.005, KTCZ/low-dose cortisol arm; and P = 0.006, KTCZ/high-dose cortisol arm). Decreased ACTH recovery in women was accompanied by lower total and free cortisol concentrations, pointing to heightened feedback inhibition of hypothalamo-pituitary drive of ACTH secretion as the main mechanism. Conclusions In summary, gender or a factor related to gender, such as sex steroids or body composition, determines recovery of ACTH secretion from cortisol-enforced negative feedback. Attenuated ACTH recovery in post-menopausal women may have relevance to sex differences in stress-related adaptations.

KW - Aging

KW - Cortisol

KW - Feedback

KW - Human

UR - http://www.scopus.com/inward/record.url?scp=84887990752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887990752&partnerID=8YFLogxK

U2 - 10.1016/j.metabol.2013.08.014

DO - 10.1016/j.metabol.2013.08.014

M3 - Article

C2 - 24074810

AN - SCOPUS:84887990752

VL - 62

SP - 1819

EP - 1829

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

SN - 0026-0495

IS - 12

ER -