The anterior pituitary gland is composed of five types of hormone-producing cells plus folliculostellate (FS) cells, which do not produce classical anterior pituitary hormones. FS cells are interconnected by cytoplasmic processes and encircle hormone-producing cells or aggregate homophilically. Using living-cell imaging of primary culture, we recently reported that some FS cells precisely extend their cytoplasmic processes toward other FS cells and form interconnections with them. These phenomena suggest the presence of a chemoattractant factor that facilitates the interconnection. In this study, we attempted to discover the factor that induces interconnection of FS cells and succeeded in identifying chemokine (CXC)-L12 and its receptor CXCR4 as potential candidate molecules. CXCL12 is a chemokine of the CXC subfamily. It exerts its effects via CXCR4, a G protein-coupled receptor. The CXCL12/CXCR4 axis is a potent chemoattractant for many types of neural cells. First, we revealed that CXCL12 and CXCR4 are expressed by FS cells in rat anterior pituitary gland. Next, to clarify the function of the CXCL12/CXCR4 axis in FS cells, we observed living anterior pituitary cells in primary culture with specific CXCL12 inhibitor or CXCR4 antagonist and noted that extension of cytoplasmic processes and interconnection of FS cells were inhibited. Finally, we examined FS cell migration and invasion by using Matrigel matrix assays. CXCL12 treatment resulted in markedly increased FS cell migration and invasion. These data suggest that FS cells express chemokine CXCL12 and its receptor CXCR4 and that the CXCL12/CXCR4 axis evokes interconnection of FS cells.

Objectives To measure current Hg, Cd, and Pb exposure in Japanese children, and to estimate dietary intakes of foods responsible for high body burden. Methods Blood, hair, and urine samples were collected from 9 to 10-year-old 229 children in Asahikawa and measured for Hg, Cd, and Pb in these matrices. Diet history questionnaire was used to estimate intake of marine foods and other food items. Hg level was measured by cold vapor atomic absorption spectrometry. Cd and Pb levels were determined with inductively coupled plasma mass spectrometry. Results Geometric mean (GM) of blood Hg, Cd, and Pb was 4.55 lg/L, 0.34 lg/L, and 0.96 lg/dL, respectively. Urinary Cd level was 0.34 lg/g creatinine (GM) and hair Hg was 1.31 lg/g (GM). Approximately one-third (35 %) of blood samples had Hg level above the U.S. EPA reference dose (RfD; 5.8 lg/L). Hair Hg level exceeded U.S. EPA RfD (1.2 lg/g) in 59 % samples. Children in the upper quartile of blood Hg level had significantly higher intake of large predatory fish species compared to those in the lower quartile of blood Hg. Conclusions Those with high blood Hg level may be explained by more frequent intake of big predatory fish. Cd and Pb exposure is generally low among Japanese children. As no safety margin exists for Pb exposure and high exposure to MeHg is noted in Japanese population; periodic biomonitoring and potential health risk assessment should continue in high-risk populations, notably among children.

Folliculostellate (FS) cells in the anterior pituitary gland are believed to have multifunctional properties. Using transgenic rats that express green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that FS cells in primary culture exhibited marked proliferation in the presence of laminin, an extracellular matrix (ECM) component of the basement membrane. In a process referred to as matricrine action, FS cells receive ECM as a signal through their receptors, which results in morphological and functional changes. In this study, we investigated matricrine signaling in FS cells and observed that the proliferation of FS cells is mediated by integrin b1, which is involved in various signaling pathways for cell migration and proliferation in response to ECM. Then, we analyzed downstream events of the integrin b1 signaling pathway in the proliferation of FS cells and identified caveolin 3 as a potential candidate molecule. Caveolin 3 is a membrane protein that binds cholesterol and a number of signaling molecules that interact with integrin b1. Using specific small interfering RNA of caveolin 3, the proliferation of FS cells was inhibited. Furthermore, caveolin 3 drove activation of the mitogen-activated protein kinase (MAPK) signaling cascades, which resulted in upregulation of cyclin D1 in FS cells. These findings suggest that matricrine signaling in the proliferation of FS cells was transduced by a caveolin 3-mediated integrin b1 signaling pathway and subsequent activation of the MAPK pathway.

Objective: Currently, there are many efforts to find functional nutrients for obesity management, and the green coffee extract is a potential candidate. This study aimed to examine the effect of low dose administration of green coffee extract on body weight, serum lipids, and TNF-α level in high-fat diet-induced obese rats. Results: Administration of green coffee extract to high-fat diet-induced obese male Wistar rats (Rattus norvegicus) reduced body weight, total serum cholesterol, and triglyceride at the dose of 10, 20, and 40 mg/kg BW/day; lowered serum LDL-cholesterol at the treatment dose of 20 mg/kg BW/day (p < 0.05). The effective dose to decrease serum TNF-α level was 40 mg/kg BW/day, while the effective dose to improve the lipid profile was 10 mg/kg BW/day. These results support the potential use of green coffee extract as a functional nutrient in the management of obesity.