This study tested the hypothesis that the sexually dimorphic adrenocortical response to stress is already established before birth. Chronically instrumented late gestation pregnant sheep carrying 16 male and 15 female age-matched singleton fetuses were subjected to an acute episode of hypoxic stress. Maternal and fetal blood gases, adrenocorticotrophic hormone (ACTH), and cortisol were measured. In addition, six male and six female fetuses received the ACTH analog, Synacthen, and plasma cortisol was measured. During hypoxic stress, the increment in plasma cortisol was 2-fold greater in male versus females fetuses (30.6 ± 3.2 versus 14.3 ± 2.0 ng/mL; p < 0.001) mediated, in part, by greater adrenocortical sensitivity to ACTH. The data support the hypothesis tested and show that sex-specific differences in the cortisol stress response are present before birth with the output of cortisol being much greater in male than in female fetuses.
Dino A Giussani1,*, Andrew J W Fletcher1 and David S Gardner1,**
1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom
Correspondence: Dino A. Giussani, Ph.D., Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom; e-mail:
*D.A.G. is a Royal Society-Wolfson Research Merit Award holder. This work was supported by the British Heart Foundation, The BBSRC, The Sir Jules Thorn Trust, The Lister Institute, and The Sir Isaac Newton Trust.
**D.S.G. is currently at The School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RA, United Kingdom.
Pediatric Research (2011) 69, 118–122 Full paper here.