Comparison of the Effects of Estradiol and Progesterone on Serotonergic Function

Department of Pharmacology, University of Texas Health Science Center at San Antonio, 78229-3900, USA.
Biological psychiatry (Impact Factor: 10.26). 01/2012; 71(7):633-41. DOI: 10.1016/j.biopsych.2011.11.023
Source: PubMed


Ovarian hormones may contribute to the vulnerability to depression, as well as to the response to antidepressants (ADs). Previously, we reported that acute systemic treatment with estradiol or progesterone blocked the ability of the selective serotonin reuptake inhibitor, fluvoxamine, to inhibit serotonin transporter function in ovariectomized rats. In this study, behavioral consequences, as well as receptor mechanisms underlying these hormonal effects, were investigated.
Using the forced swimming test, the acute effect of estradiol and/or progesterone on fluvoxamine's AD-like effects was investigated. Using in vivo chronoamperometry, the effect of local application of estradiol or progesterone into the hippocampus of ovariectomized rats on serotonin (5-HT) clearance, as well as on the ability of fluvoxamine to slow 5-HT clearance, were investigated.
The decreased immobility and increased swimming caused by fluvoxamine in the forced swimming test was blocked in rats treated with estradiol and/or progesterone. Local application of estradiol, but not progesterone, slowed 5-HT clearance and both hormones blocked the ability of fluvoxamine to slow 5-HT clearance. Use of hormone receptor agonists and antagonists, revealed that the effects of estradiol are mediated by activation of membrane, as well as nuclear estrogen receptors (ER). The AD-like effect of estradiol involved ER beta and G-protein coupled receptor 30, whereas its blockade of fluvoxamine's effects was ER alpha-mediated. The effects of progesterone occurred solely by activation of intracellular progesterone receptors.
Targeting of ER beta or G-protein coupled receptor 30 might reveal a strategy to permit beneficial effects of estrogen without its deleterious effect on selective serotonin reuptake inhibitor efficacy.

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    • "Since most regions showed similar SERT asymmetry in male and female control subjects, it seems that assumed differences in adult hormonal levels did not profoundly affect SERT asymmetry. This, however, differs from studies indicating strong effects of sex steroids on serotonin function (Benmansour et al. 2012; Robichaud and Debonnel 2005; Rubinow et al. 1998). However, in the midCC, our data show a rightward asymmetry for MC but not for FC and MtF transsexuals (Fig. 3). "
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