JES-Sponsored Symposia

2010 Endocrine journal  
Sex differences in structure and function of the brain are organized developmentally in a variety of species. In mammals, androgen secreted from the testis masculinizes the brain during a critical period of perinatal development. This steroid action causes permanent and irreversible changes in the brain. Recent evidence, however, implicates that independent of gonadal steroid, genetic sex of brain cells directly influences their sexual phenotype. Sexual differentiation of the brain is therefore
more » ... brain is therefore an area of research that is attracting intense interest. On the other hand, in teleosts, very little is known about sexual differentiation of the brain. Their phenotypic sex can be manipulated by treatment with exogenous steroid hormones even after reaching sexual maturity. In addition, not a few teleost species can spontaneously change their phenotypic sex under certain circumstances. These facts suggest that teleosts have a unique mechanism of brain sexual differentiation, which enables them to hold remarkable sexual plasticity throughout life. We used medaka (Oryzias latipes) as a model organism to elucidate the general and comparative aspects of sexual differentiation of the vertebrate brain. We screened for genes exhibiting sexually dimorphic patterns of expression in the medaka brain. One of the genes identified to be expressed predominantly in female was found to be cyp19a2. It encodes aromatase, a key steroidogenic enzyme that catalyzes the final step of estrogen biosynthesis. The expression and regulation of this gene will be discussed in the context of sexual differentiation of the medaka brain. Sex differences have been reported in structural volumes, gray/white matter partitions, functional connectivity and patterns of cerebral activation. These observations are important, as they suggest that the skewed sex distribution in several common neuropsychiatric conditions (affective, autistic disorder, ADHD, schizophrenia) may be attributed to sexual dimorphism of the brain. The underlying mechanisms are unknown. Tentative effects of fetal programming will be discussed, along with systematic survey of the current information from various brain imaging studies. Incidence of cardiovascular events in hypertensive patients with diabetes and/or obesity: Subanalysis of the CASE-J trial Objectives: The metabolic syndrome is now appreciated as an important risk factor for cardiovascular events. Here, we examined the incidence of cardiovascular events in relation to the presence of diabetes (DM) and/or obesity.Method: The CASE-J trial compared the effects of candesartan and amlodipine on the incidence of CV events in 4,728 high-risk Japanese hypertensive patients. We examined the cardiovascular events rate in them stratified by presence or absence of DM, body mass index (BMI) at baseline, and both. The mean follow-up period was 3.2 years.Results: The cardiovascular events rate was 25.5/1,000 patients years in patients with DM and 11.8/1,000 patients years in those without DM, being significantly higher in the former patients. The stratified analysis by BMI at baseline revealed that the cardiovascular events rate was 19.5/1,000 patients years in BMI < 22 kg/m 2 , 14.8 in 22 ≤ BMI <25, 18.6 in 25 ≤ BMI <27.5, and 19.9 in 27.5 ≤ BMI. The incidence of events in patients with both DM and obesity (25 ≤ BMI), corresponding to the metabolic syndrome, was 25.2/1,000 patients years and those without both DM and obesity was 10.8/1,000 patients years.Conclusion: DM was strongly associated with the risk of CV events. There was a U-shaped relation between BMI and the incidence of CV events. This subanalysis confirmed that the incidence of cardiovascular events in hypertensive patients with DM and obesity was 2.7-fold higher than those without them.
doi:10.1507/endocrj.57.s311 fatcat:mgvrxbtvizekbcby3764eanwdq