The role of serum adiponectin levels in women with polycystic ovarian syndrome.

PURPOSE OF INVESTIGATION: The aim of this study was to measure serum adiponectin concentrations in women with polycystic ovarian syndrome (PCOS) and to assess possible correlations between adiponectin and the hormonal or metabolic parameters of this syndrome. MATERIALS AND METHODS: Serum adiponectin levels were evaluated in 20 women with PCOS and 22 women without PCOS whose age and body mass index (BMI) matched the patients. The levels of fasting blood glucose, fasting insulin, gonadotropin, and sex steroid hormones were evaluated in both groups. The homeostasis model assessment (HOMA) score was also calculated. The serum adiponectin levels were assayed by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: Serum adiponectin levels were significantly lower in obese women than in normal-weight women, and they were also significantly lower in PCOS patients with HOMA scores greater than 1.7 compared with those with HOMA scores lower than 1.7. When the subjects were divided in two groups based on serum adiponectin levels (> 40 microg/ml, < 40 microg/ml), 65% of patients with PCOS were included in the lower adiponectin group (p < 0.05). In addition, gonadotropin levels were increased, dependent on the adiponectin levels in women with PCOS. CONCLUSION: Adiponectin is regarded as a possible link between adiposity and insulin resistance (IR). From this data, the secretions of gonadotropin are implicated in the levels of adiponectin in women with PCOS. It is suggested that adiponectin may play an important role in the pathogenesis of PCOS.

Involvement of resistance to apoptosis in the pathogenesis of endometriosis.

Endometriosis, a disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue. Increasingly, endometriosis is also becoming recognized as a condition in which ectopic endometrial cells exhibit abnormal proliferative and apoptotic regulation in response to appropriate stimuli. Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggests that, in healthy women, endometrial cells expelled during menstruation do not survive in ectopic locations because of programmed cell death, while decreased apoptosis may lead to the ectopic survival and implantation of these cells, resulting in the development of endometriosis. Both the inability of endometrial cells to transmit a 'death' signal and the ability of endometrial cells to avoid cell death have been associated with increased expression of anti-apoptotic factors and decreased expression of pre-apoptotic factors. This paper is a review of the recent literature focused on the differential expression of apoptosis-associated molecules in the normal endometria of women without endometriosis, and in the eutopic and ectopic endometria of women with endometriosis. The role of apoptosis in the pathogenesis of endometriosis and the basic and clinical research on the current medical treatment for endometriosis from the view of apoptosis will be discussed.

Human oviductal epithelial cells express Toll-like receptor 3 and respond to double-stranded RNA: Fallopian tube-specific mucosal immunity against viral infection.

BACKGROUND: The aim of this study was to evaluate the site-specific immunoregulatory mechanisms against viral infection in human Fallopian tubes. METHODS: We therefore investigated the effects of double-stranded RNA (dsRNA) on the production of interleukin (IL)-6, IL-8 and granulocyte chemotactic protein-2 (GCP-2) by cultured oviductal epithelial cells (OECs) using enzyme-linked immunosorbent assays. Phosphorylation of inhibitor kappaB-alpha (IkappaB-alpha) protein after dsRNA stimulation and the expression of Toll-like receptor (TLR) 3 in these cells were also evaluated by western blot analysis. RESULTS: Polyriboinosinic:polyribocytidylic acid (poly I:C), a synthetic dsRNA that antagonizes TLR3, stimulated the secretion of IL-6, IL-8 and GCP-2 by OECs. Poly I:C-induced production of these cytokines by OECs was inhibited by the pretreatment of these cells with anti-TLR3 antibody. The phosphorylation of IkappaB-alpha protein was detected in OECs after stimulation by poly I:C. The expression of TLR3 was also detected in OECs. CONCLUSION: These results suggest that the epithelial cells of the human Fallopian tube have evolved a unique, site-specific mechanism for recognizing viral infection. TLR3-mediated production of proinflammatory cytokines and chemokines in OECs in response to viral dsRNA may be important for antiviral immunity in the human female reproductive tract.

Beta-hydroxyisovalerylshikonin induces apoptosis and G0/G1 cell-cycle arrest of endometriotic stromal cells: a preliminary in vitro study.

BACKGROUND: Most of the current medical treatments for endometriosis aim to down-regulate the estrogen activity. However, a high recurrence rate after medical treatments has been the most significant problem. Beta-hydroxyisovalerylshikonin (beta-HIVS) is an ATP non-competitive inhibitor of protein-tyrosine kinases and is considered an apoptosis-inducing agent. The aim of this study is to evaluate the effects of beta-HIVS on the proliferation, cell cycle and apoptosis of endometriotic stromal cells. METHODS: We investigated the effects of beta-HIVS on cultured ovarian endometriotic cyst stromal cells (ECSC) by a modified methylthiazoletetrazolium (MTT) assay, a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and internucleosomal DNA fragmentation assays. The effect of beta-HIVS on the cell cycle of ECSC was determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSC using western blot analysis. RESULTS: Beta-HIVS significantly inhibited the proliferation and DNA synthesis of ECSC and induced apoptosis and G0/G1 phase cell-cycle arrest of these cells. Down-regulation of the B-cell lymphoma/leukaemia-2 (Bcl-2) expression with the activation of caspase-3, caspase-8 and caspase-9 was observed in ECSC after beta-HIVS treatment. CONCLUSIONS: These results suggest that beta-HIVS induces apoptosis of ECSC by suppressing anti-apoptotic proteins. Although our present findings are preliminary, beta-HIVS could potentially be a therapeutic agent for the treatment of endometriosis.

Association between Vogt-Koyanagi-Harada syndrome and HLA-DR1 and -DR4 in Hispanic patients living in southern California.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is associated with human leukocyte antigen (HLA)-B54, -DR4, -DR beta 1*0405, -DQ4, and -DR53 in Japanese patients. Disease-associated HLA specificities may differ among races. This study examined HLA associations with VKH syndrome in Hispanic patients living in southern California, a racial subgroup at increased risk for the disease. METHODS: Human leukocyte antigen specificities were determined on 25 Hispanic patients with VKH syndrome and compared with HLA specificities of 217 healthy Hispanic control subjects. Inclusion criteria for study patients were nontraumatic panuveitis with exudative retinal detachments, with or without extraocular manifestations. Tests were performed using standard cytotoxic assays. RESULTS: HLA-DR4 was present in 14 (56%) patients with VKH syndrome and in 62(29%) control subjects (relative risk = 1.96). HLA-DR1 was present in 9 (36%) patients with VKH syndrome and in 19 (9%) control subjects (relative risk = 4.11). HLA-DR1 and DR4 share a common epitope within the DR beta 1 gene. HLA-DR1 and/or DR4 were present in 21 (84%) patients with VKH syndrome and in 76 (35%) control subjects (relative risk = 2.40). CONCLUSIONS: HLA-DR1 and -DR4 were found in a significantly disproportionate number of Hispanic patients with VKH syndrome living in southern California. HLA-DR4, although not HLA-DR1, has been previously associated with VKH syndrome in other groups. These associations suggest a common immunogenic predisposition to VKH among different racial groups, and suggest that a common epitope shared by DR1 and DR4 may be involved in the pathogenesis of the disease.