Cycle and age-related changes in corticotropin-releasing hormone levels in human endometrium and ovaries

Corticotropin-releasing hormone (CRH) exerts an anti-inflammatory effect indirectly, via cortisole production, and a proinflammatory effect directly on immune cells. The aim of the present work was to examine the effect of CRH on macrophage-derived cytokines both in vitro and in vivo. For the in vitro experiments we used two types of macrophages: (i) the RAW264.7 monocyte/macrophage cell line and (ii) thioglycolate-elicited peritoneal macrophages from BALB/c mice. We have found that CRH enhanced lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), and IL-6 production. For the in vivo experiments we have used the LPS-induced endotoxin shock model in BALB/c mice, an established model for systemic inflammation in which macrophages are the major source of the proinflammatory cytokines responsible for the development of the shock. Administration of antalarmin, a synthetic CRH receptor 1 (CRHR1) antagonist, prior to LPS prolonged survival in a statistically significant manner. The effect was more evident at the early stages of endotoxin shock. CRHR1 blockade suppressed LPS-induced elevation of the macrophagederived cytokines TNF-␣, IL-1␤, and IL-6, confirming the role of CRH signals in cytokine expression. In conclusion, our data suggest that CRH signals play an early and crucial role in augmenting LPS-induced proinflammatory cytokine production by macrophages. Our data suggest that the diffuse neuroendocrine system via CRH directly affects the immune system at the level of macrophage activation and cytokine production.Corticotropin-releasing hormone (CRH) affects the immune system. This effect can be indirect, via the end products of the two major axes of the adaptive response to stress, regulated by CRH, i.e., cortisole of the hypothalamus-pituitary-adrenals (HPA) axis and catecholamines of the sympathetic system (13). CRH also affects the immune system in a direct manner. Indeed, CRH is released at the site of inflammation by nerve terminals and epithelial cells, affecting resident immune cells (13,33). It should be noted that while the indirect effect of CRH is anti-inflammatory, its direct paracrine effect is definitely proinflammatory. Thus, blockade of its paracrine effect by specific anti-CRH serum attenuates the inflammatory response in several models of inflammation in vivo (15, 33). A major immune target of CRH is the mast cell (13, 25). However, in addition to mast cells a growing list of immune cells exhibits specific CRH binding sites. Thus, mouse splenocytes (34), human peripheral blood monocytes and lymphocytes (24), and monocytes/macrophages and Th cells (2) have CRH receptors. CRH receptors are also present in inflamed synovium (9) and inflamed subcutaneous tissues (19). CRHR1 expression is upregulated by lipopolysaccharide (LPS) stimulation (22). The aim of the present work was to study the effect of CRH on macrophages, the main source of the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), and IL-6, which initiate the in...

show abstract

“…to 10 Ϫ9 M (29,36). Treatment of cells for 24 h in the presence of LPS stimulated the secretion of TNF-␣, IL-1␤, and IL-6.…”

Section: ϫ6mentioning

confidence: 99%

Corticotropin-Releasing Hormone Augments Proinflammatory Cytokine Production from Macrophages In Vitro and in Lipopolysaccharide-Induced Endotoxin Shock in Mice

Agelaki¹,

Tsatsanis²,

et al. 2002

View full text Add to dashboard Cite

show abstract

“…However, polycystic ovaries present diminished amounts of CRH immunoreactivity, suggesting that decreased ovarian CRH might be related to the anovulation of polycystic ovarian syndrome (13). Finally, the concentration of CRH is higher in the premenopausal than the postmenopausal ovaries, indicating that ovarian CRH may be related to normal ovarian function during the reproductive life span (49).…”

Section: Ovarian Crhmentioning

confidence: 97%

Peripheral corticotropin-releasing hormone is produced in the immune and reproductive systems: actions, potential roles and clinical implications

Kalantaridou

Makrigiannakis²,

Zoumakis³

et al. 2007

Front Biosci

View full text Add to dashboard Cite

Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, has been identified in various organ systems, including the immune and the female and male reproductive systems. CRH-like immunoreactivity has been reported in peripheral inflammatory sites and in a number of reproductive organs, including the ovaries, endometrial glands, decidualized endometrial stroma, placenta, decidua, and the testes. Therefore, "immune" and "reproductive" CRH are forms of "tissue" CRH; i.e., CRH found in peripheral tissues. Immune CRH plays a direct immunomodulatory role as an autocrine/paracrine mediator of inflammation. Immune CRH participates in several experimental inflammations and, in humans, in inflamed tissues from patients with autoimmune and inflammatory diseases. One of the early effects of immune CRH is the degranulation of mast cells and the release of histamine and several inflammatory cytokines. Reproductive CRH is regulating reproductive functions with an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of labor. Circulating placental CRH is responsible for the physiologic hypercortisolism of the latter half of pregnancy. Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.

show abstract

“…36 In the human periphery, CRF is expressed in adrenals (cortex and core), testis, placenta, 36,37 intestines, spleen, thymus, skin, pancreas, leucocytes, 38,39 endometrium, 40 ovaries 41 and heart. 42 In the rat, extra-hypothalamic CRF has been detected in the myenteric plexus and nervous fibers of the submucosal plexus in intestines and other tissues, such as testis, 43 ovaries, 44 thymus, spleen 45 and adrenals.…”

Section: Crf Neuropeptides and Receptors In The Peripherymentioning

confidence: 99%

The corticotropin releasing factor system in the liver: expression, actions and possible implications in hepatic physiology and pathology

Paschos¹,

Chouridou²,

Koureta³

et al. 2013

View full text Add to dashboard Cite

The corticotropin-releasing factor (crF) system plays a crucial regulatory role in the adaptation to exogenous and endogenous stress stimuli, as well as homeostasis. Apart from the central nervous system (cNs), the members of this neuropeptide family extend their actions in the periphery, where they may affect various body systems independently, stimulating peripheral crF receptors via vagal and/or autocrine/paracrine pathways. Here, we review all findings concerning the expression and role of the crF system in human liver, but also in other species. Direct and indirect regulatory data are also analyzed in order to draw conclusions about possible physiological/pathophysiological implications. Although data supporting any clinical significance are still limited and further research in the field is necessary, scientific interest in the crF system is particularly active, with multiple ongoing clinical studies evaluating the activity of crF ligands in medical conditions involving other organs. Thus, new knowledge with therapeutic potential appears to be steadily accumulating.

show abstract

Cycle and age-related changes in corticotropin-releasing hormone levels in human endometrium and ovaries

Cited by 18 publications

References 0 publications

Corticotropin-Releasing Hormone Augments Proinflammatory Cytokine Production from Macrophages In Vitro and in Lipopolysaccharide-Induced Endotoxin Shock in Mice

Corticotropin-Releasing Hormone Augments Proinflammatory Cytokine Production from Macrophages In Vitro and in Lipopolysaccharide-Induced Endotoxin Shock in Mice

Peripheral corticotropin-releasing hormone is produced in the immune and reproductive systems: actions, potential roles and clinical implications

The corticotropin releasing factor system in the liver: expression, actions and possible implications in hepatic physiology and pathology

Contact Info

Product

Resources

About