Kotaro Kunimi

β-Microseminoprotein/prostatic secretory protein is a member of immunoglobulin binding factor family

Human seminal plasma contains a factor that binds human IgG, designated as immunoglobulin binding factor (IgBF). Under reducing condition IgBF interacts with anti-Leu-11b, a murine monoclonal antibody raised against human FcgammaRIII/CD16. IgBF shows no binding activity under non-reducing condition. Three components having IgBF activity were separated by HPLC and their amino acid sequences determined. The main IgBF showed structural identity to beta-microseminoprotein (beta-MSP), prostatic secretory protein of 94 amino acids (PSP94) and beta-inhibin. The slight variation in the reported sequences of these proteins has been attributed to analytical error. In the present study the molecular masses of main IgBF and beta-MSP/PSP94 were found to be identical by mass spectrometry. In addition, a large component of IgBF and a shorter beta-MSP consisting of 93 amino acids were identified. The binding of beta-MSP for human IgG and anti-Leu-11b antibody is demonstrable only under reducing condition, determined by Western blot analysis. The present data clearly show that IgBF is a family composed of at least three isoforms. One of the members is beta-MSP/PSP94. This family should be designated as IgBF.

Association of circulating adiponectin with testosterone in women during the menopausal transition

OBJECTIVE We examined (1) the change in circulating adiponectin in women during the menopausal transition and (2) the associations of adiponectin levels with estrogen, androgen and sex hormone-binding globulin (SHBG) in women during the menopausal transition. METHODS We conducted a cross-sectional study in 235 healthy women and divided them into 7 stages by menstrual regularity and follicle-stimulating hormone (FSH) level. Serum levels of adiponectin, estradiol, total testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and SHBG were measured. Levels of free and bioavailable testosterone were calculated by using total testosterone, albumin and SHBG. RESULTS Serum adiponectin levels showed a U-curve, levels being low in early and late menopausal transition and gradually becoming higher after menopause. Adiponectin levels were negatively correlated with levels of free testosterone, bioavailable testosterone and DHEA-S and were positively correlated with SHBG in postmenopausal women for whom more than 1 year had passed since menopause. Adiponectin level was not correlated with estradiol level. CONCLUSION Circulating adiponectin level shows a U-curve during the menopausal transition and adiponectin level is associated with levels of free and bioavailable testosterone and DHEA-S in postmenopause.

Different circulating levels of monocyte chemoattractant protein-1 and interleukin-8 during the menopausal transition

OBJECTIVE The aim of the present study was to clarify the changes in circulating cytokines and chemokines in women during the menopausal transition by using a detailed classification. MATERIALS AND METHODS A total of 554 women were recruited for this study from the outpatient clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. We divided the women into seven stages by menstrual regularity and FSH level: mid-reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause, early postmenopause and late postmenopause. We measured serum concentrations of nine cytokines (IL-1β, IL-5, IL-6, IL-7, IL-8, IL-10, TNF-α, MIP-1β and MCP-1). RESULTS Serum IL-8 concentrations in postmenopausal women were significantly (p = 0.001) higher than those in women in the mid- or late reproductive stage and women in early or late menopausal transition. Serum MCP-1 levels in women in late menopausal transition and postmenopause were significantly (p < 0.001) higher than those in women in the mid- or late reproductive stage and women in early menopausal transition. MCP-1 level showed a significant positive correlation (r = 0.215, p < 0.01) with FSH level in women in menopausal transition. CONCLUSION By using a detailed classification of menopausal transition, patterns of changes in IL-8 and MCP-1 levels during the menopausal transition were found to be different. IL-8 level showed a high level after menopause, while MCP-1 level showed a high level in menopausal transition. MCP-1 may be sensitive to hormonal change and may be involved in the development of estrogen deficiency diseases.

Prepubertal exposure to glucocorticoid delays puberty independent of the hypothalamic Kiss1-GnRH system in female rats

Secretion of glucocorticoids is widely known as a key endocrine response to stresses. Prenatal dexamethasone administration induces intrauterine growth retardation and delayed onset of puberty in female rats independent of the hypothalamic Kiss1‐gonadotropin‐releasing hormone (GnRH) system. The aim of this study was to evaluate the influence of chronic intracerebroventricular (central, CD) or subcutaneous (peripheral, PD) dexamethasone administration to prepubertal female rats on the onset of puberty and body weight change. Rats administered dexamethasone from day 25 to day 34 (CD and PD) showed significantly reduced body weight gain throughout the experimental period and delayed onset of vaginal opening compared with rats administered saline centrally (CS) or peripherally (PS). At 34 days old, hypothalamic Kiss1r mRNA levels were significantly lower with CD than with CS. No significant differences were seen between rats administered saline and rats administered dexamethasone with regard to hypothalamic Kiss1, GnRH and NPY mRNA levels or serum LH levels. Serum leptin concentrations were higher in CD and PD than in the controls (CS and PS). These results suggest that the delayed onset of puberty induced by prepubertal dexamethasone administration occurs independent of the hypothalamic Kiss1‐GnRH system.

Associations of estrogen and testosterone with insulin resistance in pre- and postmenopausal women with and without hormone therapy.

Background Estrogen deficiency due to natural menopause or surgical menopause has been suggested to have an adverse effect on insulin resistance. Testosterone and sex hormone–binding globulin (SHBG) as well as estrogen are also associated with insulin resistance in women. However, to date, the associations of estradiol, testosterone and SHBG with insulin resistance according to estrogen level have not been clarified. Objectives We examined the associations of estradiol, testosterone and SHBG with insulin resistance in pre- and in postmenopausal women and postmenopausal women who had received hormone therapy to clarify whether the associations differ depending on the estrogen status. Patients and Methods Twenty premenopausal women and thirty-two postmenopausal women were enrolled in this study. Fifteen postmenopausal women received oral conjugated equine estrogen (CEE) (0.625 mg) everyday for 12 months. Serum levels of estradiol, testosterone, SHBG and insulin and plasma levels of glucose were measured. Results Serum estradiol levels tended to have a negative correlation with homeostasis model assessment of insulin resistance (HOMA-IR) in premenopausal women but not in postmenopausal women. On the other hand, free testosterone levels tended to have a positive correlation with HOMA-IR in postmenopausal women but not in premenopausal women. Serum SHBG levels showed significant negative correlations with HOMA-IR in both pre- and postmenopausal women. SHBG level was significantly increased, free testosterone level was significantly decreased and HOMA-IR was significantly decreased at 12 months after CEE administration. However, there were no significant correlations of changes between estradiol, SHBG or free testosterone and HOMA-IR. Conclusions The associations of sex steroid hormones with insulin resistance are different depending on the estrogen status.

Identification of the human sperm protein that interacts with sperm-immobilizing antibodies in the sera of infertile women

OBJECTIVE To identify the target antigen of sperm-immobilizing antibodies present in the circulation of infertile women. DESIGN Laboratory research. SETTING Academic research laboratory. PATIENT(S) Twenty-nine infertile women with sperm-immobilizing antibodies, 22 infertile women with other disorders, and 20 fertile women. INTERVENTION(S) Titers of antibodies to the sperm protein, rSMP-B, were determined by ELISA using as substrate the synthetic peptide segment (rSMP-230) that corresponds with the hydrophilic domain of rSMP-B. Tests for sperm immobilization and zona pellucida penetration were performed using the human IVF system. MAIN OUTCOME MEASURE(S) Human sera with sperm-immobilizing activity were assayed for the presence of antibodies to rSMP-230. Polyclonal antibodies to rSMP-230 were assessed for the same biologic activities as sperm-immobilizing antibodies. RESULT(S) Antibodies to rSMP-230 were detected in 10 (34%) of 29 sera obtained from women with immunologic infertility. In contrast, only one serum sample (2%) from women without sperm-immobilizing activity had a low titer of antibodies to rSMP-230. Polyclonal antibodies to rSMP-230 completely immobilized human sperm in the presence of complement and blocked sperm penetration across the zona pellucida. CONCLUSION(S) The human sperm protein, rSMP-B, probably is the target antigen of sperm-immobilizing antibodies.

Arterial stiffness is increased in young women with endometriosis

Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.

Difference in the ratio of high-molecular weight (HMW) to total adiponectin and HMW adiponectin in late post-menopausal women.

Objective: High-molecular weight (HMW) isoform level and HMW ratio have been shown to be better predictors of insulin sensitivity and metabolic syndrome than total adiponectin level. We examined the changes in circulating levels of HMW adiponectin and ratios of HMW to total adiponectin in women during the menopausal transition. Methods: We conducted a cross-sectional study in 217 healthy women and divided them into 4 stages: 58 women in pre-menopausal, 69 women in perimenopausal, 62 women in early post-menopausal and 28 women in late post-menopausal phase. Serum levels of total adiponectin and HMW adiponectin were measured by an enzyme-linked immunosorbent assay. Results: In late post-menopausal women, HMW adiponectin level was significantly higher than that in peri-menopausal women and the HMW to total adiponectin ratio was significantly lower than that in early post-menopausal women. In peri-menopausal women, HMW adiponectin level was significantly lower than that in pre-menopausal women and HMW to total adiponectin ratio was significantly lower than the ratios in pre-menopausal and early post-menopausal women. Conclusion: The ratio of HMW to total adiponectin is low in late post-menopausal women, though both levels of total and HMW adiponectin were high after menopause in our cross-sectional study.

Changes in insulin sensitivity during GnRH agonist treatment in premenopausal women with leiomyoma

OBJECTIVE The purpose of this study was to determine (1) the influence of estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist administration on insulin sensitivity as well as hormones and factors related to insulin resistance and (2) the differences in the influence for these parameters by the degree of basal insulin sensitivity. METHODS Thirty-five women diagnosed with leiomyoma were enrolled in this study. Serum levels of fasting glucose, insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular inflammatory markers and cytokines before and at 6months after commencement of GnRH agonist administration were examined. RESULTS In all women, levels of insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly changed. However, in women who had a low HOMA-IR before treatment, levels of insulin, glucose and HOMA-IR showed significant increases and total testosterone level showed a significant decrease. In women who had a high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased and levels of highly sensitive C-reactive protein, soluble intercellular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly increased. CONCLUSION Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment.