Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin f3 subunit to the follitropin (8 subunit (biologic Communicated by Oliver H. Lowry, February 5, 1992 ABSTRACT Follitropin (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. FSH is used clinically to stimulate follicular maturation for in vitro fertilization and treatment of anovulatory women. One issue regarding the clinical use of FSH is its short half-life in the circulation. To address this point, we constructed chimeric genes containing the sequence encoding the C-terminal peptide of the chorionic gonadotropin 13 subunit (CG1) fused to the translated sequence of the human FSH P subunit (FSH(8). This region of CGI3 is important for maintaining the prolonged plasma half-life of human CG dimer. The presence of the C-terminal peptide sequence did not significantly affect assembly of FSH(3 with the a subunit or secretion of the dimer. In vitro receptor binding and steroidogenic activity of dimer bearing the FSHf-Cterminal peptide chimera were the same as wild-type FSH.However, both the in vivo potency and half-life in circulation of the dimer bearing either one or two C-terminal peptide units were enhanced. Dimers containing FSH(-CGI3 chimeras could serve as potent FSH agonists for clinical use, and the present strategy may have wide applications for enhancing the in vivo half-life of diverse proteins.
The parental origin of the missing short arm of the X chromosome has an impact on overweight, kidney, eye, and lipids, which suggests a potential effect of an as-yet-undetermined X chromosome gene imprinting.
Light-at-night (LAN) is a worldwide problem co-distributed with breast cancer prevalence. We hypothesized that exposure to LAN is coincided with a decreased melatonin (MLT) secretion level, followed by epigenetic modifications and resulted in higher breast cancer tumors growth-rate. Accordingly, we studied the effect of LAN exposure and exogenous MLT on breast cancer tumors growth-rate. 4T1 cells were inoculated into BALB/c short day-acclimated mice, resulting in tumors growth. Growth rates were followed under various light exposures and global DNA methylations were measured. Results demonstrated the positive effect of LAN on tumors growth-rate, reversed by MLT through global DNA methylation.
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