The gene encoding for the novel transacting factor proopiomelanocortin corticotropin-releasing hormone responsive element binding protein 1 (PCRH-REB-1) is constitutively expressed in rat pituitary and in discrete brain regions containing CRH or CRH receptors: pathophysiological implications.

Stress during childhood and adolescence has implications for the extent of depression and psychotic disorders in maturity. Stressful events lead to the regression of synapses with the loss of synaptic spines and in some cases whole dendrites of pyramidal neurons in the prefrontal cortex, a process that leads to the malfunctioning of neural networks in the neocortex. Such stress often shows concomitant increases in the activity of the hypothalamic–pituitary–adrenal system, with a consequent elevated release of glucocorticoids such as cortisol as well as of corticotropin-releasing hormone (CRH) from neurons. It is very likely that it is these hormones, acting on neuronal and astrocyte glucocorticoid receptors (GRs) and CRH receptors, respectively, that are responsible for the regression of synapses. The mechanism of such regression involves the loss of synaptic spines, the stability of which is under the direct control of the activity of N-methyl-d-aspartate (NMDA) receptors on the spines. Glutamate activates NMDA receptors, which then, through parallel pathways, control the extent in the spine of the cytoskeletal protein F-actin and so spine stability and growth. Both GR and CRH receptors in the spines can modulate NMDA receptors, reducing their activation by glutamate and hence spine stability. In contrast, glucocorticoids, probably acting on nerve terminal and astrocyte GRs, can release glutamate, so promoting NMDA receptor activation. It is suggested that spine stability is under dual control by glucocorticoids and CRH, released during stress to change the stability of synaptic spines, leading to the malfunctioning of cortical neural networks that are involved in depression and psychoses.

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Identification and characterization of a corticotrophin-releasing hormone receptor in human placenta

Acta Endocrinologica ◽

10.1530/eje.0.1330591 ◽

1995 ◽

Vol 133 (5) ◽

pp. 591-597 ◽

Cited By ~ 28

Author(s):

Vicki L Clifton ◽

Phillip C Owens ◽

Phillip J Robinson ◽

Roger Smith

Keyword(s):

Human Placenta ◽

Binding Sites ◽

Hormone Receptor ◽

Human Myometrium ◽

Scatchard Analysis ◽

Releasing Hormone ◽

Rat Pituitary ◽

Identification And Characterization ◽

Crh Receptors

Clifton VL, Owens PC, Robinson PJ, Smith R. Identification and characterization of a corticotrophinreleasing hormone receptor in human placenta. Eur J Endocrinol 1995;133:591–7. ISSN 0804–4643 Corticotrophin-releasing hormone (CRH) causes vasodilatation in the human fetal–placental circulation and has paracrine actions in placental tissue, suggesting that CRH receptors may be present in the human placenta. We have now identified and characterized placental CRH binding sites and compared them to those described previously in human myometrium and rat pituitary. Radiolabelled ovine CRH binding to placental membranes was pH-, time-, temperature- and divalent cation-dependent and was reversible in the presence of 1 μmol/l unlabelled ovine CRH. Scatchard analysis of placentae delivered vaginally or by elective caesarean section revealed dissociation constants (Kd) of 214.5 ± 84 pmol/l (N = 8) and 45.4 ± 23.9 pmol/l (N = 9), respectively. The Kd for caesarean placental binding sites was similar to that of human myometrium (59.6 pmol/l, N = 3) and rat pituitary (82.5 pmol/l, N = 3) receptors. However, in vaginally delivered placentae the CRH binding sites had a much lower affinity (p < 0.05). The receptor densities (Bmax) of vaginally delivered and caesarean-delivered placentae were 28.6 ± 9.6 and 6.1 ± 2.8 fmol/mg, respectively (p < 0.05). Chemical cross-linking studies using disuccinimidyl suberate indicated that the molecular weight of the CRH receptor in the placenta and rat pituitary is 75 kD. We conclude that there is a high-affinity population of CRH binding sites in the human placenta that are physicochemically similar to pituitary and myometrial CRH receptors. The CRH receptor properties in the placenta change in response to labour, when CRH levels in maternal blood are highest, suggesting that placental CRH may regulate its receptor. R Smith, Endocrinology Unit, John Hunter Hospital, Locked Bag 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia

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Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes

Reproduction Fertility and Development ◽

10.1071/rd10341 ◽

2011 ◽

Vol 23 (6) ◽

pp. 780 ◽

Cited By ~ 11

Author(s):

Magdalena Ciechanowska ◽

Magdalena Łapot ◽

Tadeusz Malewski ◽

Krystyna Mateusiak ◽

Tomasz Misztal ◽

...

Keyword(s):

Gene Expression ◽

Pituitary Gland ◽

Anterior Pituitary ◽

Follicular Phase ◽

Gnrh Receptor ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Gonadotrophin Releasing Hormone ◽

Lh Secretion ◽

Crh Receptors

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo–pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo–anterior pituitary unit.

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The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation

Biomedicines ◽

10.3390/biomedicines8120623 ◽

2020 ◽

Vol 8 (12) ◽

pp. 623

Author(s):

Haiyan Zheng ◽

Ji Yeon Lim ◽

Jae Young Seong ◽

Sun Wook Hwang

Keyword(s):

Signal Transmission ◽

Brain Regions ◽

Pain Modulation ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Inhibitory Function ◽

Peripheral Pain ◽

Functional Profiles ◽

Pituitary Adrenal Axis

Peripheral nociceptors and their synaptic partners utilize neuropeptides for signal transmission. Such communication tunes the excitatory and inhibitory function of nociceptor-based circuits, eventually contributing to pain modulation. Corticotropin-releasing hormone (CRH) is the initiator hormone for the conventional hypothalamic-pituitary-adrenal axis, preparing our body for stress insults. Although knowledge of the expression and functional profiles of CRH and its receptors and the outcomes of their interactions has been actively accumulating for many brain regions, those for nociceptors are still under gradual investigation. Currently, based on the evidence of their expressions in nociceptors and their neighboring components, several hypotheses for possible pain modulations are emerging. Here we overview the historical attention to CRH and its receptors on the peripheral nociception and the recent increases in information regarding their roles in tuning pain signals. We also briefly contemplate the possibility that the stress-response paradigm can be locally intrapolated into intercellular communication that is driven by nociceptor neurons. Such endeavors may contribute to a more precise view of local peptidergic mechanisms of peripheral pain modulation.

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