A quantitative study of the pulsatile parameters of CRH-41 secretion in unanesthetized free-moving rats

Ixart, G.; Barbanel, Gérard; Nouguier-Soulé, J; Assenmacher, I

doi:10.1007/bf00228516

Cited by 41 publications

(36 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, studies in the sheep have shown that ultradian rhythms of ACTH and CORT are maintained even after the hypothalamus has been surgically disconnected from the pituitary (Engler et al 1990), suggesting there must be a hypothalamic-independent pulse generator. Further supporting this idea is the observation that in the rat there is a mismatch between the frequency of CRH pulses (w3 pulses/h) (Ixart et al 1991) and the near-hourly frequency of ACTH and CORT oscillations (Carnes et al 1988a).…”

Section: The Origin Of Glucocorticoid Pulsatilitymentioning

confidence: 92%

“…Furthermore, episodic release of CRH has been shown in macaque (Mershon et al 1992), sheep (Caraty et al 1988, Engler et al 1989, and the rat (Ixart et al 1991(Ixart et al , 1994. The evidence of pulsatility of CRH led to the acceptance that the ultradian release of CORT was driven by a hypothalamic CRH pulse generator.…”

Section: The Origin Of Glucocorticoid Pulsatilitymentioning

confidence: 99%

See 1 more Smart Citation

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Spiga¹,

Walker²,

Gupta³

et al. 2015

Journal of Endocrinology

View full text Add to dashboard Cite

A pulsatile pattern of secretion is a characteristic of many hormonal systems, including the glucocorticoid-producing hypothalamic-pituitary-adrenal (HPA) axis. Despite recent evidence supporting its importance for behavioral, neuroendocrine and transcriptional effects of glucocorticoids, there has been a paucity of information regarding the origin of glucocorticoid pulsatility. In this review we discuss the mechanisms regulating pulsatile dynamics of the HPA axis, and how these dynamics become disrupted in disease. Our recent mathematical, experimental and clinical studies show that glucocorticoid pulsatility can be generated and maintained by dynamic processes at the level of the pituitary-adrenal axis, and that an intra-adrenal negative feedback may contribute to these dynamics.

show abstract

Section: The Origin Of Glucocorticoid Pulsatilitymentioning

confidence: 92%

Section: The Origin Of Glucocorticoid Pulsatilitymentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Spiga¹,

Walker²,

Gupta³

et al. 2015

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Although there is some evidence for pulsatility of CRH (1,2), our recent work suggests that ACTH and CORT pulsatility is predominantly generated by a subhypothalamic oscillator within the pituitary-adrenal system (3,4). The amplitude of these pulses varies in a circadian manner with larger pulses occurring at the start of the active phase (morning in humans, evening in rodents).…”

mentioning

confidence: 98%

“…contributed equally to this work. 2 To whom correspondence should be addressed. Email: f.spiga@bristol.ac.uk.…”

mentioning

confidence: 99%

Dynamic responses of the adrenal steroidogenic regulatory network

Spiga

Zavala

Walker

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The hypothalamic-pituitary-adrenal axis is a dynamic system regulating glucocorticoid hormone synthesis in the adrenal glands. Many key factors within the adrenal steroidogenic pathway have been identified and studied, but little is known about how these factors function collectively as a dynamic network of interacting components. To investigate this, we developed a mathematical model of the adrenal steroidogenic regulatory network that accounts for key regulatory processes occurring at different timescales. We used our model to predict the time evolution of steroidogenesis in response to physiological adrenocorticotropic hormone (ACTH) perturbations, ranging from basal pulses to larger stress-like stimulations (e.g., inflammatory stress). Testing these predictions experimentally in the rat, our results show that the steroidogenic regulatory network architecture is sufficient to respond to both small and large ACTH perturbations, but coupling this regulatory network with the immune pathway is necessary to explain the dissociated dynamics between ACTH and glucocorticoids observed under conditions of inflammatory stress. T he hypothalamic-pituitary-adrenal (HPA) axis is a stressresponsive neuroendocrine system that controls circulating levels of the vital glucocorticoid (CORT) hormones corticosterone (in rodents) and cortisol (in humans). These are steroids synthesized by the adrenal gland in response to stimulation by adrenocorticotropic hormone (ACTH), which is secreted by the anterior pituitary in response to corticotrophin-releasing hormone (CRH) and arginine vasopressin released from hypothalamic paraventricular neurons. These neurons receive circadian inputs from the suprachiasmatic nucleus and are activated in response to stress. Via the bloodstream, CORT accesses target tissues where it mediates metabolic, cognitive, and immune responses. CORT also regulates its own production through negative feedback inhibition of ACTH and CRH secretion from the pituitary and hypothalamus, respectively. To mount an effective response to stress, CORT must be secreted rapidly by the adrenal glands. However, because of its lipophilic nature, CORT cannot be prestored in vesicles and must therefore be rapidly synthesized de novo in response to ACTH stimulation.Under basal, unstressed conditions, ACTH and CORT exhibit ultradian oscillations. Although there is some evidence for pulsatility of CRH (1, 2), our recent work suggests that ACTH and CORT pulsatility is predominantly generated by a subhypothalamic oscillator within the pituitary-adrenal system (3, 4). The amplitude of these pulses varies in a circadian manner with larger pulses occurring at the start of the active phase (morning in humans, evening in rodents). Under normal physiological conditions, CORT secretion is tightly correlated with ACTH (5). However, there are a number of conditions where a dynamic dissociation between these hormones occurs (reviewed in ref. 6). For example, there is evidence that proinflammatory cytokines released during inflammation can poten...

show abstract

“…Indeed, there is evidence for episodic release of CRH from macaque hypothalamic explants (Mershon et al 1992) and for rapid changes in CRH in the median eminence of rats (Ixart et al 1991) and portal blood of sheep (Caraty et al 1988). There is, however, a mismatch between the higher frequency of CRH pulses than the ACTH/CORT pulses, and Engler et al (1990) also demonstrated the maintenance of ACTH and cortisol pulses in the sheep even after disconnection of the pituitary from hypothalamic portal blood.…”

Section: The Origin Of Hpa Pulsatilitymentioning

confidence: 99%

Rhythms Within Rhythms: The Importance of Oscillations for Glucocorticoid Hormones

Lightman

2016

Research and Perspectives in Endocrine Interactions

View full text Add to dashboard Cite

The circadian activity of the hypothalamic-pituitary-adrenal (HPA) axis is made up from an underlying oscillatory rhythm of ACTH and glucocorticoid pulses that vary in amplitude but not frequency over the 24 h. This oscillatory activity is not the result of a hypothalamic oscillator but emerges as a natural consequence of the feedforward:feedback interaction between the pituitary corticotropes and the glucocorticoid-secreting cells of the adrenal cortex. This oscillatory activity has resulted in adaptations in the way tissues read their 'digital' ligand signal. The adrenal cortex is relatively insensitive to constant signals of ACTH but responds briskly to the equivalent amount of ACTH administered in a pulsatile manner. Similarly glucocorticoid-responsive tissues such as the brain and the liver are able to read the oscillating signals of cortisol or corticosterone secretion, with differential biochemical and functional responses to different patterns of ligand presentation. During a prolonged acute stress there is a major change in the pituitary-adrenal relationship, with a marked increase in the sensitivity of the adrenal to small changes in ACTH, so that following cardiac surgery small oscillations in ACTH result in massive swings in cortisol. This response appears to be due to a change both in the ACTH signalling pathway and in the endogenous activators and inhibitors of glucocorticoid synthesis.

show abstract

A quantitative study of the pulsatile parameters of CRH-41 secretion in unanesthetized free-moving rats

Cited by 41 publications

References 23 publications

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Dynamic responses of the adrenal steroidogenic regulatory network

Rhythms Within Rhythms: The Importance of Oscillations for Glucocorticoid Hormones

Contact Info

Product

Resources

About