The odorous steroid androstadienone, a putative male chemo-signal, was previously reported to evoke sex differences in hypothalamic activation in adult heterosexual men and women. In order to investigate whether puberty modulated this sex difference in response to androstadienone, we measured the hypothalamic responsiveness to this chemo-signal in 39 pre-pubertal and 41 adolescent boys and girls by means of functional magnetic resonance imaging. We then investigated whether 36 pre-pubertal children and 38 adolescents diagnosed with gender dysphoria (GD; DSM-5) exhibited sex-atypical (in accordance with their experienced gender), rather than sex-typical (in accordance with their natal sex) hypothalamic activations during olfactory stimulation with androstadienone. We found that the sex difference in responsiveness to androstadienone was already present in pre-pubertal control children and thus likely developed during early perinatal development instead of during sexual maturation. Adolescent girls and boys with GD both responded remarkably like their experienced gender, thus sex-atypical. In contrast, pre-pubertal girls with GD showed neither a typically male nor female hypothalamic activation pattern and pre-pubertal boys with GD had hypothalamic activations in response to androstadienone that were similar to control boys, thus sex-typical. We present here a unique data set of boys and girls diagnosed with GD at two different developmental stages, showing that these children possess certain sex-atypical functional brain characteristics and may have undergone atypical sexual differentiation of the brain.
Keywords: androstadienone, chemo-signal, fMRI, gender dysphoria, hypothalamus, puberty, sex difference
Citation: Burke SM, Cohen-Kettenis PT, Veltman DJ, Klink DT and Bakker J (2014) Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents. Front. Endocrinol. 5:60. doi: 10.3389/fendo.2014.00060
Received: 21 November 2013; Accepted: 10 April 2014;
Published online: 28 May 2014.
Edited by:Hubert Vaudry, University of Rouen, France
Reviewed by:Alexander S. Kauffman, University of California San Diego, USA
Copyright: © 2014 Burke, Cohen-Kettenis, Veltman, Klink and Bakker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sarah M. Burke, Center of Expertise on Gender Dysphoria, Neuroscience Campus Amsterdam, Department of Medical Psychology, VU University Medical Center, De Boelelaan 1131, Amsterdam 1081 HX, Netherlands e-mail: firstname.lastname@example.org