Relation of progesterone and DHEAS serum levels to 5-HT1A receptor binding potential in pre- and postmenopausal women

Preclinical research and clinical experience point to a modulation of 5-HT1A receptor expression by gonadal steroid hormones. We examined the effect of estradiol, progesterone and DHEAS on serotonin neurotransmission in 16 premenopausal and 28 postmenopausal women, differentiating by reproductive status. By means of positron emission tomography and the radiotracer [carbonyl-11C]WAY-100635, the 5-HT1A receptor binding potential (BP) was quantified in 45 brain regions of interest. Median BP was used as a surrogate marker to estimate the whole brain effect of the steroid hormones on receptor binding. We found a strong negative effect of serum progesterone and DHEAS levels on 5-HT1A receptor binding in postmenopausal women both in the Median BP and on a regional level. Furthermore, there was a non-linear, U-shaped relationship between DHEAS levels and 5-HT1A receptor binding in the pooled sample. Presynaptic 5-HT1A receptor BP in the raphe nuclei was significantly explained in a non-linear way by both progesterone and DHEAS in the pooled sample. Our study confirms in humans a preclinically suggested relation of the steroid hormones progesterone and DHEAS to 5-HT1A receptor binding. We show differential effects of the hormones with regard to reproductive hormonal status. Non-linear, U-shaped relationships between hormone serum concentrations and serotonin neurotransmission might explain paradoxical effects of these hormones on mood.