The Prevention of Preterm Labour - Corticotropin Releasing Hormone Type 1 Receptors as a Target for Drug Design and Development

Keller, P. A.; Kirkwood, Kimberly S.; Morgan, Jody; Westcott, Stephen A.; McCluskey, Adam

doi:10.2174/1389557033488105

Cited by 11 publications

(10 citation statements)

References 44 publications

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“…However, it has been shown by a series of in vitro studies, that CRH is released from cultured human placenta cells in a dose-dependent manner in response to cortisol, catecholamines, oxytocin, angiotensin-II and both types of interleukin-1. 28,29 In our present study the increased CRH production may result from increased TNF-α concentrations. Furthermore, the stronger association between TNF-α and CRH levels that was observed in our study among women with preterm labor may indicate that a critical level of CRH should be reached for the initiation of labor.…”

Section: Discussionsupporting

confidence: 52%

Association between serum tumor necrosis factor‐α and corticotropin‐releasing hormone levels in women with preterm labor

Vitoratos

Papadias

Makrakis

et al. 2006

J of Obstet and Gynaecol

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Section: Discussionsupporting

confidence: 52%

Association between serum tumor necrosis factor‐α and corticotropin‐releasing hormone levels in women with preterm labor

Vitoratos

Papadias

Makrakis

et al. 2006

J of Obstet and Gynaecol

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“…The actions of placental-derived CRH and CRHrelated agonists during human pregnancy are exceedingly complex. The suggestion that CRH may act as a "placental clock" determining the length of pregnancy is extremely attractive and in certain cases of threatened pregnancy, such as pre-term labour, might warrant the use of preventative measures to adjust the function of this "clock" (64,65). Specific CRH-R antagonists for potential pharmacological interventions are available; however, characterization of their biological and physiological roles is not yet, complete.…”

Section: Discussionmentioning

confidence: 99%

The role of CRH receptors and their agonists in myometrial contractility and quiescence during pregnancy and labour

Grammatopoulos¹

2007

Front Biosci

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The mechanism of human labor remains a scientific enigma. Corticotropin-releasing hormone (CRH), a hypothalamic peptide that controls the response of the body to stress and which is also produced by the placenta and intrauterine tissues during pregnancy is potentially involved in the onset of labor. CRH is part of a family of mammalian peptides that includes the urocortins (UCNs), which are also expressed by the placenta and intrauterine tissues. During human pregnancy, CRH appears to target multiple feto-maternal tissues, including the myometrium, implicating CRH in the regulation of the transition from relaxation to active uterine contractions. The myometrial actions of CRH are mediated via a wide network of specific G-protein coupled membrane-bound receptors. These receptors have various functional properties, depending on the receptor subtype, the ability of agonists to activate specific signalling cascades and the stage of pregnancy. In addition, their function is dependent upon other intracellular signals via communication between signalling cascades, suggesting potential multiple roles of CRH and other CRH-like peptides during pregnancy and labor. This review will provide the current concepts about the role of CRH and UCNs and their myometrial receptors during pregnancy, labor and delivery.

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“…2) (both type 1 and type 2) whose activity and expression appears to be dynamically regulated during pregnancy and labour. Their role is not fully understood, although their presence in the myometrium coupled to the pattern of placental CRH secretion, which peaks at term and the onset of labour, led many investigators to propose that the placental CRH ⁄ myometrial CRH-R system is actively involved in the onset of labour (32). However, subsequent studies primarily based on in vitro cellular and molecular models raised the possibility that the primary role of this system is to prevent premature myometrial contractions, and to allow pregnancy to reach term when the delivered foetus will have more chances of survival.…”

Section: Placental Vascular Tonementioning

confidence: 99%

Placental Corticotrophin‐Releasing Hormone and its Receptors in Human Pregnancy and Labour: Still a Scientific Enigma

Grammatopoulos

2008

J Neuroendocrinology

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It is now accepted that, in humans, placental corticotrophin‐releasing hormone (CRH) is involved in the mechanisms controlling the onset of labour; however, the precise biological role in foeto–maternal tissues remain enigmatic. Maternal plasma levels of CRH rise exponentially as pregnancy progresses towards term and peak during labour; however, evidence to link this with an active role in the onset and progression of labour, is still inconclusive. Certainly, one of the tissues targeted by CRH is the myometrial smooth muscle, which expresses a plethora of specific CRH receptors. This finding implicates CRH in the mechanisms preparing the myometrial microenvironment for the onset of labour and possibly in the regulation of active contractility during labour. Other gestational tissues also targeted by CRH include the placenta, foetal membranes and foetal adrenals, where CRH might regulate distinct physiological functions, ranging from control of vascular tone to adrenal steroidogenesis and prostaglandin synthesis and activity. Given the unique, among mammals, pattern of human placental CRH secretion and CRH receptor expression and signalling during pregnancy and labour, there are only limited biological tools available to delineate the actions of CRH in foeto–maternal tissues, primarily based on in vitro characterisation of the signalling and molecular events driven by CRH. This review will set in context the current concepts about the role of CRH and its receptors during pregnancy and labour, focusing on the unresolved questions and paradoxes that currently exist.

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The Prevention of Preterm Labour - Corticotropin Releasing Hormone Type 1 Receptors as a Target for Drug Design and Development

Cited by 11 publications

References 44 publications

Association between serum tumor necrosis factor‐α and corticotropin‐releasing hormone levels in women with preterm labor

Association between serum tumor necrosis factor‐α and corticotropin‐releasing hormone levels in women with preterm labor

The role of CRH receptors and their agonists in myometrial contractility and quiescence during pregnancy and labour

Placental Corticotrophin‐Releasing Hormone and its Receptors in Human Pregnancy and Labour: Still a Scientific Enigma

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