The corticotropin releasing hormone gene is expressed in human placenta

Grino, Michel; Chrousos, George P.; Margioris, Andrew N.

doi:10.1016/s0006-291x(87)80261-9

Cited by 182 publications

(82 citation statements)

References 19 publications

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“…Whereas in previous studies non-quantitative or semi-quantitative methods were applied (e.g. Grino et al 1987, Petraglia et al 1993, 1996, Clifton et al 1998, Watanabe et al 1999, Florio et al 2000, Wetzka et al 2003 we investigated differential mRNA expression patterns by using real-time quantitative RT-PCR. CRH and CRH-BP mRNA was mainly expressed by placenta.…”

Section: Discussionmentioning

confidence: 99%

mRNA expression profiles for corticotrophin-releasing hormone, urocortin, CRH-binding protein and CRH receptors in human term gestational tissues determined by real-time quantitative RT-PCR

Sehringer

Hp²,

Simon³

et al. 2004

Journal of Molecular Endocrinology

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Increasing maternal plasma levels of corticotrophin-releasing hormone (CRH) during the last weeks of pregnancy suggest that this stress hormone plays an important role in the control of human parturition. Little is known about the quantitative contribution of gestational tissues (other than placenta) to intrauterine formation of CRH, urocortin and CRH-binding protein (CRH-BP), or about the distribution of CRH receptors within the uterus.We have investigated the mRNA expression of CRH, urocortin, CRH-BP and CRH receptors 1 and 2 (CRH-R1 and -R2) in gestational tissues by real-time RT-PCR. Placenta, myometrium and choriodecidua were collected after uncomplicated pregnancies at term, before the onset of labour. Distribution of CRH-R1 and CRH-R2 protein was also investigated by immunostaining with receptor subtype-specific antibodies.The placenta was identified as the main site of CRH and CRH-BP mRNA expression, displaying mRNA levels >1000 and >20 times higher than those found in the myometrium and choriodecidua respectively (P<0·05 in each case). mRNA expression of urocortin was low in all tissues investigated. Myometrium and choriodecidua expressed relevant amounts of both receptor subtypes, whereas the CRH receptor population in placenta consisted mainly of CRH-R2.The high expression of CRH in placenta and the substantial expression of CRH receptors in choriodecidua and myometrium suggested that CRH derived from placenta exerts direct or indirect actions on these tissues. Neither CRH produced by myometrium or choriodecidua nor urocortin from other intrauterine sources seem to play a major role in the control of labour.

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Section: Discussionmentioning

confidence: 99%

mRNA expression profiles for corticotrophin-releasing hormone, urocortin, CRH-binding protein and CRH receptors in human term gestational tissues determined by real-time quantitative RT-PCR

Sehringer

Hp²,

Simon³

et al. 2004

Journal of Molecular Endocrinology

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“…Although both Grino et al (8) and ourselves (9, 12) have found that the human term placenta secretes mainly the hCRH,,-size form in vitro, the placenta may also secrete such larger forms in vivo. Similar larger forms of CRH-IR have been found in the blood plasma of pregnant women (2-4) although it is not known if they are also bioactive.…”

Section: Large Crh-ir Is Bioactive 97mentioning

confidence: 86%

“…It has been shown that the hormone, first isolated in ovine hypothalami (7) and responsible for the release of adrenocorticotrophin (ACTH), /?-endorphin (PEP) and related peptides from the anterior pituitary (7), is present in human placental extracts (1)(2)(3). The discovery of messenger RNA transcripts in the human placenta (8) and the demonstration of bioactive placental CRH-IR (1) and its release from placental cells in vitro (8,9) indicate placental synthesis and secretion of the peptide. With the discovery of a specific CRH binding protein in the human blood circulation (lo), it has been postulated that the elevated CRH-1R during pregnancy is proteinbound and not bioactive, to account for an absence of a significant elevation of plasma ACTH during pregnancy (1 1).…”

mentioning

confidence: 99%

Large Molecular Weight Immunoreactive Corticotrophin‐Releasing Hormone has Bioactivity on Superfused Ovine Pituitary Cells

Chan

Thomson

Madsen

et al. 1990

J Neuroendocrinology

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“…There have not been noted any sex or age differences in plasma ACTH or F responses to CRH (10). Moreover, although ACTH response to CRH is not influenced by the hour of the day, the corresponding F response is maximized late in the afternoon (11).…”

Section: Introductionmentioning

confidence: 85%

“…Peripheral CRH has been found in the adrenal medulla, testes, ovaries, cardiovascular system, gastrointestinal tract, pancreas, lung, spinal cord, endometrium, and placenta (11)(12)(13)(14)(15)(16), as well as in diverse inflammatory sites (1,17,18). Peripheral sensory afferent type C fibers and postganglionic sympathetic nerves also express CRH (19) and have been suggested as one more source of immune CRH.…”

Section: Introductionmentioning

confidence: 99%

Corticotropin releasing hormone and the immune/inflammatory response

Mastorakos¹,

Karoutsou²,

Mizamtsidi³

2006

eur j endocrinol

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Hypothalamic corticotropin-releasing hormone (CRH) acts as the major physiologic ACTH secretagog. Moreover, CRH is distributed in the brain and spinal cord, adrenal medulla, testes, ovaries, gastrointestinal tract, pancreas, myometrium, endometrium, placenta, and diverse inflammatory sites. Immunoreactive CRH has been found in the cytoplasm of immune accessory cells (macrophages, endothelial cells, and tissue fibroblasts), and in inflammatory sites of both acute and chronic inflammation (synovial lining cell layers and blood vessels from the joints of patients with rheumatoid arthritis and osteoarthritis). Additionally, the local presence of CRH in the uveitic eyes, cytoplasm of inflammatory cells (macrophages, lymphocytes, and polymorphonuclear cells) infiltrating the iris, ciliary body, vitreous, retina, and choroid appears to be of pivotal importance in the process of experimental autoimmune uveoretinitis. Traditionally, hypothalamic CRH has been considered to act indirectly in an anti-inflammatory fashion, since the end product of the hypothalamic-pituitaryadrenal axis is cortisol, a well-known anti-inflammatory compound. However, CRH produced at peripheral inflammatory sites has been shown to participate in an autocrine/paracrine stimulation of inflammation. Thus, CRH may have a peripheral, primarily activating role on the immune system. The mechanisms of the CRH-mediated component of the immune/inflammatory response are still unclear. CRH in inflammatory sites seems to be involved in the activation of the Fas/Fas ligand system. Furthermore, locally produced embryonic and endometrial CRH plays a role in both the aseptic inflammatory process of implantation and the anti-rejection process that protects the fetus from the maternal immune system. There are two types of G-protein-coupled CRH receptors (CRH-R1 and CRH-R2). Pyrrolopyrimidine compounds, such as antalarmin, have been developed as CRH-R1 receptor antagonists. Confirming the peripheral pro-inflammatory actions of CRH, antalarmin has been shown to suppress experimental aseptic inflammation. Thus, antalarmin may represent the first in a new class of anti-inflammatory agents operating through CRH-R1. Studies of CRH genetics have provided new insights on the pathogenesis of rheumatoid arthritis in humans. DNA variation across the CRH genecontaining region has been examined in families with multiple cases of rheumatoid arthritis. Transmission Disequilibrium Test analysis showed significant association at the CRH locus.European Journal of Endocrinology 155 S77-S84

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The corticotropin releasing hormone gene is expressed in human placenta

Cited by 182 publications

References 19 publications

mRNA expression profiles for corticotrophin-releasing hormone, urocortin, CRH-binding protein and CRH receptors in human term gestational tissues determined by real-time quantitative RT-PCR

mRNA expression profiles for corticotrophin-releasing hormone, urocortin, CRH-binding protein and CRH receptors in human term gestational tissues determined by real-time quantitative RT-PCR

Large Molecular Weight Immunoreactive Corticotrophin‐Releasing Hormone has Bioactivity on Superfused Ovine Pituitary Cells

Corticotropin releasing hormone and the immune/inflammatory response

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