An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: 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. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy

Several anthropometric measurements and breast cancer risk: results of the E3N cohort study.

OBJECTIVE: To investigate the association between various anthropometric characteristics and breast cancer. DESIGN: Longitudinal prospective cohort study. Follow-up between 1995 and 2000.Subjects:In total, 69 116 women (age: 45-70 years; mean follow-up: 3.6 years), 275 premenopausal and 860 postmenopausal incident invasive breast cancers. MEASUREMENTS: Self-reported height, weight, breast, thorax, waist and hip circumferences and calculated body mass index (BMI) and waist-to-hip ratio (WHR) at baseline. RESULTS: A slight increase in risk with increasing height was found. Weight, BMI, thorax and waist circumferences and WHR were negatively related to breast cancer risk among premenopausal women. The relationships became non significant after additional adjustment for BMI. An increased risk of premenopausal breast cancer with an android body shape (WHR>0.87) might possibly be confined to obese women. Among postmenopausal women, all anthropometric measurements of corpulence were positively associated with breast cancer risk but became non significant after additional adjustment for BMI. No difference in risk of postmenopausal breast cancer according to HRT use was observed. CONCLUSION: The study confirmed that adiposity was negatively associated to premenopausal breast cancer risk and positively associated to postmenopausal breast cancer risk. Further studies will be needed to specify clearly the association between WHR and breast cancer risk, particularly before menopause