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DC Field | Value | Language |
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dc.contributor.author | Markovic, D | - |
dc.contributor.author | Chen, J | - |
dc.contributor.author | Hillhouse, EW | - |
dc.contributor.author | Grammatopoulos, DK | - |
dc.date.accessioned | 2014-05-19T14:48:29Z | - |
dc.date.available | 2014-05-19T14:48:29Z | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | Endocrinology, 151(10), 4959 - 4968, 2010 | en_US |
dc.identifier.issn | 0013-7227 | - |
dc.identifier.uri | http://press.endocrine.org/doi/full/10.1210/en.2010-0622 | en |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/8454 | - |
dc.description | Copyright © 2010 by The Endocrine Society. | en_US |
dc.description.abstract | Two types of CRH receptors mediate the diverse biological functions of CRH and CRH-related peptides. The type 1 CRH-R (CRH-R1) is extensively targeted by pre-mRNA splicing mechanisms that give rise to multiple mRNA splice variants. RT-PCR amplification of CRH-R1 sequences from human myometrium yielded cDNAs that encode a novel CRH-R1 splice variant with structural characteristics identical with CRH-R1β except a 14-amino acid deletion in the seventh transmembrane domain characteristic of the CRH-R1d. Transient expression of the hybrid CRH-R1 variant (CRH-R1β/d) in human embryonic kidney 293 cells revealed primarily intracellular expression, although some plasma membrane protein expression was also detectable. CRH bound to CRH-R1β/d with affinity comparable with the CRH-R1β; however, it was unable to stimulate adenylyl cyclase or other second messengers. Using a semiquantitative RT-PCR assay, CRH-R1β/d mRNA transcript was detected in human pregnant, but not nonpregnant, myometrium as early as 31 wk of gestation. Furthermore, in human pregnant myometrial cells, the relative expression of CRH-R1β and CRH-R1β/d mRNA appeared to be regulated by steroids; CRH-R1β/d mRNA expression was increased by estradiol-17β, whereas CRH-R1β mRNA levels were increased by progesterone. Progesterone also substantially increased CRH-R1α mRNA levels and cellular responsiveness to CRH as determined by increased agonist binding and cAMP production as well as resistance to CRH-R heterologous desensitization by phorbol esters. These results provide novel evidence for distinct patterns of CRH-R1 splicing and identify specific steroid-mediated regulation of CRH-R1 variant expression, which might be important for modulating CRH actions during human pregnancy and labour. | en_US |
dc.description.sponsorship | Wellcome Trust | en_US |
dc.language.iso | en | en_US |
dc.publisher | Endocrine Society | en_US |
dc.subject | Corticotropin-releasing hormone (CRH) | en_US |
dc.subject | CRH receptors | en_US |
dc.subject | CRH peptides | en_US |
dc.subject | Human pregnant myometrium | en_US |
dc.title | Identification of a novel corticotropin-releasing hormone type 1β-like receptor variant lacking exon 13 in human pregnant myometrium regulated by estradiol-17β and progesterone | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1210/en.2010-0622 | - |
pubs.organisational-data | /Brunel | - |
pubs.organisational-data | /Brunel/Brunel Active Staff | - |
pubs.organisational-data | /Brunel/Brunel Active Staff/School of Health Sciences & Social Care | - |
pubs.organisational-data | /Brunel/Brunel Active Staff/School of Health Sciences & Social Care/Biological Sciences | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Centre for Cell and Chromosome Biology | - |
Appears in Collections: | Biological Sciences Publications Dept of Life Sciences Research Papers |
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