%0 Journal Article
%T An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology
%A Leszek A Rybaczyk
%A Meredith J Bashaw
%A Dorothy R Pathak
%A Scott M Moody
%A Roger M Gilders
%A Donald L Holzschu
%J BMC Women's Health
%D 2005
%I BioMed Central
%R 10.1186/1472-6874-5-12
%X We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone.Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation.In mammalian females, estrogen that acts extracellularly is primarily produced in the reproductive organs, and concentrations in blood serum and other tissues change over the lifespan and within the ovarian cycle[1]. The most active and most studied form of estrogen in mammals is 17-¦Â estradiol (hereafter E2), although less active forms are also present [2]. Changes in E2 typically occur in conjunction with changes in progesterone, and are to some degree dependent on progesterone priming. In this paper, we will primarily focus on physiological levels of E2 assuming the presence of progesterone between puberty and menopause, and assuming its absence after menopause. Differences in estrogen concentrations are associated with physiological changes affecting the central nervous system (CNS), skeletal, vascular, and immune systems. The mechanisms producing some of these changes have yet to be fully elucidated [3].Estrogen receptors and s
%U http://www.biomedcentral.com/1472-6874/5/12