Endogenous plasma estradiol in healthy men is positively correlated with cerebral cortical serotonin 2A receptor binding.
BACKGROUND
Sex-hormones influence brain function and are likely to play a role in the gender predisposition to mood and anxiety disorders. Acute fluctuations of sex-hormone levels including hormonal replacement therapy appear to affect serotonergic neurotransmission, but it is unknown if baseline levels affect serotonergic neurotransmission. This study was undertaken to examine if baseline levels of endogenous sex hormones are associated with cerebral serotonin 2A (5-HT(2A)) receptor binding in men.


METHODS
In a group of 72 healthy men (mean age 37.5 years ±17.4 SD, range 19.6-81.7) we studied the effect of plasma sex hormone levels on neocortical 5-HT(2A) receptor binding as imaged with [(18)F]altanserin PET. The effect of endogenous sex-hormone levels was evaluated by multiple linear regression analysis.


RESULTS
Mean neocortical 5-HT(2A) receptor binding was positively correlated with estradiol (p=0.0001), whereas no independent effects of testosterone could be demonstrated. Correction for other factors of importance for 5-HT(2A) receptor binding did not change the result. A voxel-based analysis suggested that there were no regional differences in the estradiol effect on cortical 5-HT(2A) receptor binding.


CONCLUSIONS
Our data show a positive correlation between endogenous plasma estradiol levels and cortical 5-HT(2A) receptor binding in healthy men, whereas, no independent effect of testosterone was demonstrated. We speculate that this association could be mediated through effects on gene transcription.
Frokjaer
Vibe G
VG
Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital, Copenhagen, Denmark. vibe@nru.dk
Erritzoe
David
D
Juul
Anders
A
Nielsen
Finn Arup
FA
Holst
Klaus
K
Svarer
Claus
C
Madsen
Jacob
J
Paulson
Olaf B
OB
Knudsen
Gitte M
GM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D004958:Estradiol / Q000097:blood*; D005462:Fluorine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D006262:Health; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D055815:Young Adult
D005462:Fluorine Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; D004958:Estradiol; C071983:altanserin; D007650:Ketanserin