We examined the expression of the protein and mRNA of the newly cloned isoform of human gonadotrophin-releasing hormone (GnRH-II) in the normal human endometrium during the menstrual cycle. Nested RT-PCR and sequence analysis revealed that two spliced variants of GnRH-II mRNA were expressed during the entire menstrual cycle, with the shorter transcript having a 21 nucleotide deletion in the region coding for GnRH-associated peptide. Using immunohistochemistry, we identified immunoreactive GnRH-II in both stromal and glandular epithelial cells during the entire menstrual phase. The immunostaining intensity was stronger during the early and mid-secretory phase compared with the proliferative and late-secretory phase. A large amount of immunoreactive GnRH-II was localized in the apical pole of the glandular lumen. Our results show that the second isoform of GnRH (GnRH-II) is expressed in the human endometrium during the entire menstrual phase. We also suggest that an increased expression of endometrial GnRH-II peptide, noted during the early and mid-secretory phase, may play an important role in human embryo implantation.
p53, one of the most important tumor suppressor proteins, plays an essential role in regulating the cell cycle and apoptosis by sensing the integrity of genome. Therefore, the level of p53 protein is critical for normal cellular homeostasis, and is known to be subtly regulated by ubiquitination and deubiquitination systems. Numerous genetic alterations of p53 have been reported in all types of tumors. In hematopoietic tumors, the mutations of p53 gene are rare compared with solid tumors, which showed more than 50% frequency for p53 mutations. According to this characteristic feature of hematological tumors, the therapeutic strategy for targeting the level of p53 may be valuable in anti-cancer treatment of hematological tumors. Herein, we deal with the posttranslational regulation of p53 via its specific ubiquitinating enzymes (Mdm2, Mdmx, COP1, Pirh2, ARF-BP1/Mule, and CHIP) and a deubiquitinating enzyme, herpesvirusassociated ubiquitin-specific protease (HAUSP). In this article, we review the regulatory mechanism of p53 via ubiquitination and deubiquitination system and suggest the several possible therapeutic strategies of targeting HAUSP, a deubiquitinating enzyme for p53, for treating hematopoietic tumors. Contents
This study was aimed to evaluate the efficacy of a single administration of long-acting gonadotrophin-releasing hormone agonist (GnRHa) as compared with daily administrations of short-acting GnRHa in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) cycles. The mean dosage of recombinant follicle-stimulating hormone (rFSH) required for COH (2,354.5±244.2 vs. 2,012.5±626.1 IU) and the rFSH dosage per retrieved oocyte (336.7±230.4 vs. 292.1±540.4 IU) were significantly higher in the long-acting GnRHa group (N=22) than those in the short-acting GnRHa group (N=28) (p<0.05). However, the mean number of visit to the hospital that was required before ovum pick-up (3.3±0.5 vs. 22.2±2.0) and the frequency of injecting GnRHa and rFSH (12.8±1.2 vs. 33.5±3.5) were significantly decreased in the long-acting GnRHa group (p<0.0001). The clinical pregnancy rate, implantation rate, and early pregnancy loss rate were not significantly different between the 2 groups. So, we suggest that a single administration of long-acting GnRHa is a useful alternative for improving patient's convenience with clinical outcomes comparable to daily administrations of short-acting GnRHa in COH for IVF-ET cycles.
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