GnRH (gonadotropin-releasing hormone) is well-known as the central regulator of the reproductive system through its stimulation of gonadotropin release from the pituitary. Progress in studies on GnRH demonstrated that GnRH has both inhibitory and stimulatory effects on cell proliferation depending on the cell type, and the mechanisms of these effects have been intensively studied. However, even human GnRH receptors which mediate GnRH stimulation have not been completely identified. In the present study, we showed that the inhibitory and stimulatory effects of GnRH on colony-formation using four cell lines and have demonstrated that the inhibitory and stimulatory effects of GnRH exhibit distinctly different patterns of ligand sensitivity. This result strongly suggests that the two opposite effects of GnRH occur via different types of GnRH receptors, however expressional analyses of human GnRH receptors did not exhibit the significantly different pattern between negatively and positively responding cell lines. Then, in order to identify the GnRH receptors involved in the two opposite effects, effects of GnRH were analysed under the conditions that human GnRH receptors were knocked down by the technique of RNA interference. Consequently, it was found that human type II GnRH receptor mediates GnRH stimulation and its splice variant determines the direction of the response to GnRH. These results are the first clear evidence for the functionality of human type II GnRH receptor. Therefore our novel findings are quite noticeable and will greatly contribute to the studies on the mechanisms of the effects of GnRH on cell proliferation in the future.
The incidence of hip fractures is increasing in Japan and is high among women older than 70 years. While osteoporosis has been identified as one of the causative factors of fracture, atypical femoral fracture has emerged as a potential complication of bisphosphonate therapy. Atypical femoral fracture is prevalent among Asian women and has been attributed to morphological parameters. Age-related decreases in the morphological parameters of the femoral diaphysis, such as cortical bone thickness, cortical cross-sectional area, and the cortical index, were reported in Japanese women prior to bisphosphonate drugs being approved for treatment. Thus, in the present study, the relationships between biomechanical and morphological parameters were analyzed using a CT-based finite element method.
1 July 2005 in The Journal of Steroid Biochemistry and Molecular Biology
A morphological analysis of ancient human bones is essential for understanding life history, medical history, and genetic characteristics. In addition to external measurements, a three‐dimensional structural analysis using CT will provide more detailed information. The present study examined adult male human skeletons excavated from Hegi cave, Nakatsu city, Oita Prefecture. CT images were taken from the femurs of adult males (Initial/Early Jomon Period (n = 10) and Late Jomon Period (n = 5)). Cross‐sectional images of the diaphysis from below the lesser trochanter to above the adductor tubercle were obtained using the method established by Imamura et al. (2019) and Imamura et al. (2021). Using Excel formulas and macros, the area of cortical bone, thickness, and degree of curvature were quantitatively analyzed. The results were compared with data on modern Japanese. The maximum thickness of cortical bone in the diaphysis and the degree of the anterior curvature were significantly greater in Late Jomon humans than in the other groups. In contrast to modern humans, the majority of Jomon femurs showed the S‐shaped curvature with the medial side at the top position and the lateral side at the lower position. The present results demonstrate that Late Jomon humans had a wider range of activity than the other groups and also provide insights into diseases in the hip and knee joints of Jomon humans.
30 September 2024 in Journal of Orthopaedic Research