これまでの研究と今後の目標

It has been revealed that reproductive function and metabolic function interact with each other. Disturbance of metabolic/nutritional conditions suppress reproductive functions and consequently induce ovulatory disorder and infertility. Some hypothalamic neuroendocrine factors are involved in these alterations. Conversely, gonadal hormonal milieu affects metabolic/nutritional functions and stress response, and these actions of androgens are drastically changed by estrogen milieu. These interactions may play pivotal role in homeostasis and adaption to some adverse conditions

Effects of verapamil and lidocaine on two components of the re-entry circuit of verapamil-sensitive idiopathic left ventricular tachycardia

AbstractOBJECTIVESWe characterized pharmacologically the slow conduction zone of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) with regard to the late diastolic potential (LDP).BACKGROUNDWe showed that the slow conduction zone of ILVT could be divided into two components by LDP; that is, the distal component with a tachycardia-dependent conduction delay property and the proximal one without it.METHODSElectrophysiologic studies were performed in eight consecutive patients. The LDP was recorded during left ventricular (LV) mapping during ILVT. Entrainment was performed from the right ventricular outflow tract while recording LDP. The effects of lidocaine (1 mg/kg body weight) and verapamil (0.5 or 1.0 mg) were examined during entrainment.RESULTSThe LDPs preceding the Purkinje potential (PP) were serially recorded from the upper third to the middle of the LV septum along the narrow longitudinal line. The ventricular tachycardia (VT) cycle length increased after lidocaine (p < 0.05), and further after verapamil (p < 0.05). The increments in the VT cycle length after administration of the drugs strongly correlated with those in LDP-PP (r > 0.9 for both drugs). The interval from the ventricular potential to LDP was unchanged after administration of the drugs. In one patient, verapamil terminated VT by local conduction block between LDP and PP. The LDP-PP measured during entrainment increased after lidocaine, and further after verapamil, whereas the interval from the stimulus to LDP remained unchanged.CONCLUSIONSThe component distal to LDP is mainly calcium channel-dependent and partly depressed sodium channel-dependent. The proximal component is considered to be sodium channel-dependent (normal)

Effects of oxytocin in postmenopausal rats

Recent studies have revealed that the administration of oxytocin has beneficial effects on the regulation of body weight, food intake, and metabolic functions, especially in obese individuals. Obesity is common in women after the menopause and drives many components of metabolic syndrome. Weight gain in menopausal women has been frequently reported. Although obesity and associated metabolic disorders are frequently observed in peri- and postmenopausal women, there are few medical interventions for these conditions. In this study, we evaluated the effects of chronic oxytocin administration on appetite, body weight, and fat mass in peri- and postmenopausal female rats. Sixteen naturally premenopausal or menopausal rats were intraperitoneally injected with oxytocin (1,000 μg/day) for 12 days. The daily changes in their body weight and food intake were measured at the same time as the oxytocin and vehicle injections. Intraperitoneally administering oxytocin for 12 days significantly reduced food intake, body weight, and visceral adipocyte size. In addition, oxytocin administration caused reductions in serum triglyceride and low-density lipoprotein-cholesterol levels, while it did not disturb hepatic or renal functions or locomotor activity. This is the first study to show the effects of oxytocin on the metabolic and feeding functions of peri- and postmenopausal female rats. Oxytocin might be a useful treatment for metabolic disorders caused by the menopause or aging

Activin stimulated follicular growth

As the follicular environment transits from being activin dominant to inhibin dominant during folliculogenesis, it is assumed that activin plays an important role in the early stage of follicular growth. We examined the effects of activin on morphological, biochemical and molecular changes in isolated preantral follicles. Preantral follicles were mechanically isolated from 14-day old female C57BL/6 mice. Each follicle was cultured and observed for 14 days using an in vitro follicle culture system containing FSH, FSH + activin A and FSH + inhibin in the culture medium. We subsequently examined FSH receptor (FSH-R) mRNA expression in isolated follicle cultures with or without activin on days 0 and 2. Activin was observed to significantly stimulate follicle enlargement on days 2, 4, 6 and 8, accelerate morphological changes and increase estradiollevels in culture medium on days 4, 12 and 14. In contrast, inhibin did not alter follicular growth. Additionally, activin stimulated the expression of FSH-R mRNA in isolated granulosa cells. It was demonstrated that activin stimulated the growth of preantral follicles, mainly during the early stage of folliculogenesis, by inducing FSH-R expression, in an isolated follicle culture system

経皮的冠動脈形成・ステント留置術症例における動脈硬化指標と日常作業活動度の解析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 山崎 力, 東京大学教授 小野 稔, 東京大学准教授 江頭 正人, 東京大学講師 赤澤 宏, 東京大学講師 大門 雅夫University of Tokyo(東京大学

Effects of chronic testosterone administration on the degree of preference for a high-fat diet and body weight in gonadal-intact and ovariectomized female rats

Energy balance and reproductive functions are closely linked in some species. The sex hormones (estrogens and androgens) are involved in the regulation of appetite, metabolism, body weight (BW), and body composition in mammals. Previously, we showed that the effects of testosterone on BW, appetite, and fat weight were markedly affected by alterations to the gonadal hormonal milieu. In this study, we examined whether testosterone administration changes food preferences and whether these effects of testosterone depend on gonadal status in female rats. We also evaluated the underlying mechanisms responsible for these effects, focusing on hypothalamic inflammation and endoplasmic reticulum (ER) stress. In gonadal-intact (sham) female rats, chronic testosterone administration promoted a preference for a high-fat diet (HFD) and increased BW gain, fat weight, and adipocyte size, whereas no such effects were observed in ovariectomized (OVX) rats. Testosterone administration increased hypothalamic interleukin-1 mRNA expression in the sham rats, but not the OVX rats. On the contrary, testosterone administration decreased the hypothalamic mRNA levels of ER stress-response genes in the OVX rats, but not the sham rats. These testosterone-induced alterations in OVX rats might represent a regulatory mechanism for preventing hypothalamic inflammation and the overconsumption of a HFD. In conclusion, testosterone’s effects on food preferences and the subsequent changes were affected by gonadal status. Testosterone-induced changes in hypothalamic inflammatory cytokine production and ER stress might be related to these findings

monochorionic dizygotic twin with some blood chimerism

We report a very rare case of monochorionic dizygotic twins conceived spontaneously. The fetuses were sex-discordant in ultrasonography in spite of monochorionic twins. After birth, the girl and boy showed normal phenotypes but they showed blood chimerism in karyotype and blood group type

Sonographic size of newborn testis

Purpose : It is essential to determine normative data of testicular size and penile length in newborn infants in order to assess the development during the fetal period. In this study, we evaluated testicular volumes using ultrasonography and also measured penile lengths in Japanese newborn infants. We also examined the associations of the development of these organs with factors including placental weight and anthropometric data. Methods : One hundred and fifteen full-term male newborn infants were recruited for this study. Testicular size was measured by ultrasonography. Results : Mean testicular volumes were 187.4 mm3 in the right testis and 185.4 mm3 in the left testis, and there was no significant difference between the right and left testicular volumes. Right and left testicular volumes showed positive and significant correlations with body lengths and weights. Testicular volumes in the right and left sides were not significantly associated with penile lengths. In 4 groups according to gestational weeks, testicular volume increased significantly with advance of gestational weeks in the left testis. Conclusion : We determined testicular volumes using ultrasonography in Japanese newborn infants. We believe that the results for newborn infants provide important information for assessment of the development of fetal testicular volume

The effects of ovariectomy and lifelong high-fat diet

In females, ovarian hormones play pivotal roles in metabolic, appetite, and body weight regulation. In addition, it has been reported that ovarian hormones also affect longevity in some species. Recently, it was found that the consumption of a high-fat diet aggravates ovariectomy-associated metabolic dysregulation in female rodents. The aim of this study was to investigate the hypothesis that long-term high-fat diet consumption and ovariectomy interact to worsen body weight regulation and longevity in female rats. At 21 days of age, female rats were weaned and randomly divided into two groups, one of which was given the high-fat diet, and the other was supplied with standard chow. At 23 weeks of age, each group was further divided into ovariectomized and sham-operated groups, and then their body weight changes, food intake, and longevity were measured until 34 months of age. The sham – high-fat diet rats exhibited greater body weight changes and higher feed efficiency than the sham – standard chow rats. On the other hand, the ovariectomized – high-fat diet and ovariectomized - standard chow rats displayed similar body weight changes and feed efficiency. The sham – high-fat diet and ovariectomized – standard chow rats demonstrated similar body weight changes and feed efficiency, indicating that the impact of ovariectomy on the regulation of body weight and energy metabolism might be similar to that of high-fat diet. Contrary to our expectations, ovariectomy and high-fat diet consumption both had small favorable effects on longevity. As the high-fat diet used in the present study not only had a high fat content, but also had a high caloric content and a low carbohydrate content compared with the standard chow, it is possible that the effects of the high-fat diet on body weight and longevity were partially induced by its caloric/carbohydrate contents. These findings indicate that the alterations in body weight and energy metabolism induced by ovariectomy and high-fat diet might not directly affect the lifespan of female rats

GnIH and Stress-Induced Reproductive Dysfunction

Physical and psychological stressors suppress hypothalamic–pituitary–gonadal axis activity and sexual behavior and consequently induce reproductive dysfunction. Recently, it has been shown that gonadotropin-inhibitory hormone (GnIH), also called RFamide-related peptide 3 (RFRP) in mammals, which is a potent inhibitory regulator of gonadotropin-releasing hormone (GnRH) and gonadotropin, is involved in stress-induced reproductive dysfunction. GnIH/Rfrp (the gene coding RFRP-3) expression and activity are increased by psychological and immune stress, and this alteration suppresses GnRH and gonadotropin secretion. Glucocorticoid acts as a mediator that interacts between stress and hypothalamic GnIH/RFRP-3. GnIH/RFRP-3 also plays important roles in stress-induced suppression of sexual behavior and infertility, and genetic silencing of GnIH/Rfrp completely recovers sexual behavior and fertility. This review summarizes what is currently known about the roles of GnIH in stress-induced reproductive dysfunction