CCKergic System, Hypothalamus-Pituitary-Adrenal (HPA) Axis, and Early-Life Stress (ELS)

Tang, Mingxi; Joseph, Anu; Chen, Qian; Jiao, Jianwei; Tang, Yaping

doi:10.5772/52042

Cited by 2 publications

(8 citation statements)

References 144 publications

(142 reference statements)

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“…Because of the paucity of studies of the effects of CCK on birds, the studies referenced here were conducted in mammals. CCK is an enteroendocrine hormone associated with hunger and anxiety ( 41 , 42 ). In female rock doves exposed to restraint stress, CCK increases in the pituitary but does not respond to exogenous CORT treatment.…”

Section: Discussionmentioning

confidence: 99%

Isolating the Role of Corticosterone in the Hypothalamic-Pituitary-Gonadal Transcriptomic Stress Response

et al. 2021

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Investigation of the negative impacts of stress on reproduction has largely centered around the effects of the adrenal steroid hormone, corticosterone (CORT), and its influence on a system of tissues vital for reproduction—the hypothalamus of the brain, the pituitary gland, and the gonads (the HPG axis). Research on the action of CORT on the HPG axis has predominated the stress and reproductive biology literature, potentially overshadowing other influential mediators. To gain a more complete understanding of how elevated CORT affects transcriptomic activity of the HPG axis, we experimentally examined its role in male and female rock doves (Columba livia). We exogenously administrated CORT to mimic circulating levels during the stress response, specifically 30 min of restraint stress, an experimental paradigm known to increase circulating CORT in vertebrates. We examined all changes in transcription within each level of the HPG axis as compared to both restraint-stressed birds and vehicle-injected controls. We also investigated the differential transcriptomic response to CORT and restraint-stress in each sex. We report causal and sex-specific effects of CORT on the HPG transcriptomic stress response. Restraint stress caused 1567 genes to uniquely differentially express while elevated circulating CORT was responsible for the differential expression of 304 genes. Only 108 genes in females and 8 in males differentially expressed in subjects that underwent restraint stress and those who were given exogenous CORT. In response to elevated CORT and restraint-stress, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary. The known functions of these genes suggest potential influence of elevated CORT on immune function and prolactin synthesis. Gene expression unique to each sex indicated that elevated CORT affected more gene transcription in females than males (78 genes versus 3 genes, respectively). To our knowledge, this is the first study to isolate the role of CORT in HPG genomic transcription during a stress response. We present an extensive and openly accessible view of the role corticosterone in the HPG transcriptomic stress response. Because the HPG system is well conserved across vertebrates, these data have the potential to inspire new therapeutic strategies for reproductive dysregulation in multiple vertebrate systems, including our own.

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Section: Discussionmentioning

confidence: 99%

Isolating the Role of Corticosterone in the Hypothalamic-Pituitary-Gonadal Transcriptomic Stress Response

et al. 2021

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“…An example of one gene of interest that is associated with limbic activation of the stress response is CCK (cholecystokinin). CCK is an enteroendocrine hormone associated with hunger and anxiety (Chen et al, 2010; Tang et al, 2012). In female rock doves exposed to restraint stress, CCK increases in the pituitary but does not respond to exogenous CORT treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In female rock doves exposed to restraint stress, CCK increases in the pituitary but does not respond to exogenous CORT treatment. Acute and chronic stress in the paraventricular nucleus (PVN) of the hypothalamus has been associated with increased expression of CCK (Tang et al, 2012), which may act as a neurotransmitter or neuromodulator in the brain (Hill et al, 1987) and interact with multiple neurotransmitter systems (e.g., dopaminergic, serotonergic, GABAergic; Tang et al, 2012). CCK may also interact with the HPA axis, including corticotropin-releasing factor (CRF), to modulate stress-related physiological responses and behaviors (Tang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Acute and chronic stress in the paraventricular nucleus (PVN) of the hypothalamus has been associated with increased expression of CCK (Tang et al, 2012), which may act as a neurotransmitter or neuromodulator in the brain (Hill et al, 1987) and interact with multiple neurotransmitter systems (e.g., dopaminergic, serotonergic, GABAergic; Tang et al, 2012). CCK may also interact with the HPA axis, including corticotropin-releasing factor (CRF), to modulate stress-related physiological responses and behaviors (Tang et al, 2012). Its predominance throughout the brain and limbic system suggests a role in the interaction between neurotransmitter systems, the HPA axis, and the limbic system during stress (Hill et al, 1987; Tang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…CCK may also interact with the HPA axis, including corticotropin-releasing factor (CRF), to modulate stress-related physiological responses and behaviors (Tang et al, 2012). Its predominance throughout the brain and limbic system suggests a role in the interaction between neurotransmitter systems, the HPA axis, and the limbic system during stress (Hill et al, 1987; Tang et al, 2012). Thus, the function of CCK as a neuromodulator and in the stress response could have wide-ranging physiological and endocrinological impacts.…”

Section: Discussionmentioning

confidence: 99%

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Isolating the role of corticosterone in the hypothalamic-pituitary-gonadal genomic stress response

Austin

Harris

Booth

et al. 2020

Preprint

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The negative impacts of stress on reproduction have long been studied. A large focus of investigation has centered around the effects of the adrenal steroid hormone corticosterone (CORT) on a system of tissues vital for reproduction, the hypothalamus of the brain, the pituitary gland, and the gonads (the HPG axis). Investigations of the role of CORT on the HPG axis have predominated the stress and reproductive biology literature, potentially overshadowing other influential mediators. To gain a more complete understanding of how elevated CORT, characteristic of the stress response, affects the activity of the HPG axis, we experimentally examined its role at the level of the genome in both male and female rock doves (Columba livia). We exogenously administrated CORT to mimic circulating levels during the stress response, specifically 30 min of restraint stress, an experimental paradigm known to increase circulating corticosterone in vertebrates. We examined all changes in genomic transcription within the HPG axis as compared to both restraint-stressed birds and vehicle-injected controls, as well as between the sexes. We report causal and sex-specific effects of CORT on the HPG stress response at the level of the transcriptome. Restraint stress caused 1567 genes to uniquely differentially express while elevated circulating CORT was responsible for the differential expression of 304 genes. Only 108 genes in females and 8 in males differentially expressed in subjects who underwent restraint stress and those who were given exogenous CORT. In response to CORT elevation characteristic of the stress response, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary. The known functions of these genes suggest potential influence of elevated CORT on immune function and prolactin synthesis. Gene expression unique to each sex indicated that elevated CORT affected more gene transcription in females than males (78 genes versus 3 genes, respectively). To our knowledge, this is the first study to isolate the role of CORT in HPG genomic transcription during a stress response. These results provide novel targets for new lines of further investigation and therapy development. We present an extensive and openly accessible view of the role corticosterone in the HPG genomic stress response, offering novel gene targets to inspire new lines of investigation of stress-induced reproductive dysfunction. Because the HPG system is well-conserved across vertebrates, these data have the potential to inspire new therapeutic strategies for reproductive dysregulation in multiple vertebrate systems, including our own.

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CCKergic System, Hypothalamus-Pituitary-Adrenal (HPA) Axis, and Early-Life Stress (ELS)

Cited by 2 publications

References 144 publications

Isolating the Role of Corticosterone in the Hypothalamic-Pituitary-Gonadal Transcriptomic Stress Response

Isolating the Role of Corticosterone in the Hypothalamic-Pituitary-Gonadal Transcriptomic Stress Response

Isolating the role of corticosterone in the hypothalamic-pituitary-gonadal genomic stress response

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