57 research outputs found
The evolution and nomenclature of GnRH-type and corazonin-type neuropeptide signaling systems
The work of the authors reported in this review was supported by grants from the BBSRC (BB/M001644/1; BB/M001032/1), the Leverhulme Trust (RGP-2013-351) and the China Scholarship Council
Recommended from our members
Immunocytochemical Localization of Growth Hormone-Releasing Factor in the Rat Hypothalamus
Recommended from our members
Abstract 4769: Growth hormone-releasing hormone (GHRH) antagonist attenuates cell motility of human endometrial cancer by down-regulating Twist and N-Cadherin expression
Recommended from our members
Treatment of experimental DMBA induced mammary carcinoma with Cetrorelix (SB-75): a potent antagonist of luteinizing hormone-releasing hormone
Recommended from our members
Corticotropin Releasing Factor (CRF): Origin and Course of Afferent Pathways to the Median Eminence (ME) of the Rat Hypothalamus
8–10 days after making various lesions in the rat hypothalamus, the presence of corticotropin releasing factor (CRF) immunoreactive neural structures was studied in paraffin and vibratome sections with CRF immunocytochemistry. (1) Bilateral anterolateral deafferentation of the medial basal hypothalamus (MBH) caused complete disappearance of CRF immunoreactivity from the median eminence (ME) in brains where the posterior edge of the cut reached the level of the pituitary stalk. A shorter cut resulted in positive immunostaining caudal to the caudal edge of the cut. (2) Unilateral deafferentation of the MBH caused significant decrease in CRF immunostaining in the ipsilateral ME. (3) Unilateral posterolateral deafferentation of the MBH caused no changes in CRF immunostaining in the rostral ME, while fewer CRF-containing processes were observed in the more caudal regions. (4) A horizontal cut ventral to the paraventricular nuclei (PVN) caused a slight decrease in the number of CRF-immunoreactive profiles in the ME. A wider and complete unilateral horizontal cut resulted in a significant decrease in CRF immunoreactivity on the operated side. Following various surgical interventions, hormone accumulation in cell bodies was detected in the paraventricular, periventricular preoptic, dorsomedial, periventricular, lateral and posterior hypothalamic, and premammillary nuclei. Fibers arising from most of these nuclei formed a fan-like projection to the ME. The majority of the CRF-fibers ran through the lateral tract of the fan, and reached the ME by the lateral-basal retrochiasmatic area (LBRCA). Scattered fibers were detected in the lateral-basal hypothalamus as far caudally as the level of the pituitary stalk. Unilateral anterolateral and horizontal cuts did not result in complete disappearance of CRF immunoreactivity from the ipsilateral ME, indicating the existence of CRF-fibers of contralateral origin in the ME
Recommended from our members
hormone-releasing hormone (GHRH) antagonist on ovarian cancer cells through the EGFR-Akt pathway
Background: Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various human cancers. Methods: MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results: In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV)1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR) level and the phosphorylation of Akt (p-Akt), suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions: The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells
Recommended from our members
Antitumor effects of the cytotoxic luteinizing hormone-releasing hormone analog AN-152 on human endometrial and ovarian cancers xenografted into nude mice
Recommended from our members
Growth hormone-releasing hormone antagonist induces apoptosis of human endometrial cancer cells through PKCδ-mediated activation of p53/p21
The growth hormone-releasing hormone (GHRH) antagonists have been shown to inhibit growth of human cancer cells, but the underlying molecular mechanisms and their actions have not been fully investigated. In this study, we first showed that GHRH-R splice variant 1 (SV1) was expressed in two human endometrial cancer cell lines, Ishikawa and ECC-1. By using MTT assay, immunoblotting for cleaved caspase-3 and TUNEL assays, we found that cell growth inhibition and apoptosis were induced in GHRH antagonist, JMR-132-treated cells by activating PKCδ and could be inhibited by treatment with PKC inhibitor, GF109203X. In addition, activation and protein expression of p53 as well as the expression of its downstream effector, p21, were increased by JMR-132 treatment. Moreover, JMR-132-induced p53 and p21 expression were diminished by treatment with PKC inhibitor. Knockdown of endogenous p53 and p21 by siRNAs abolished the JMR-132-induced cell growth inhibition and apoptosis. This study demonstrates a novel mechanism in which GHRH antagonist-induced cell growth inhibition and apoptosis through PKCδ-mediated activation of p53/p21 in human endometrial cancer cells. These findings may suggest the feasibility of GHRH antagonists as a therapeutic approach for human cancer
Recommended from our members
Biological effects and receptor binding affinities of new pseudononapeptide bombesin/GRP receptor antagonists with N-terminal d-Trp or d-Tpi
- …