Episodic secretion of ACTH in rats

Carnes, Molly; Brownfield, Mark S.; Kalin, Ned H.; Lent, Stephanie J.; Barksdale, Charles M.

doi:10.1016/0196-9781(86)90216-0

Cited by 43 publications

(17 citation statements)

References 34 publications

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“…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 Pulsatilitysupporting

confidence: 49%

“…With respect to HPA axis rhythmicity, pulsatility of ACTH has been described in the rat (Carnes et al 1986(Carnes et al , 1988a, sheep (Apostolakis et al 1992) and human (Henley et al 2009a). 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.…”

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

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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.

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Section: The Origin Of Glucocorticoid Pulsatilitysupporting

confidence: 49%

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

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“…ACTH injection resulted in a rapid and transient increase in plasma ACTH ( Fig. 2A) with a peak concentration comparable to the peak of endogenous ultradian ACTH pulses (26,27). This was accompanied by a rapid and dynamic increase in CORT secretion, detectable in both adrenal tissue (A-CORT; Fig.…”

Section: Resultsmentioning

confidence: 99%

Dynamic responses of the adrenal steroidogenic regulatory network

Spiga

Zavala

Walker

et al. 2017

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

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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...

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“…Contrary to the corticosterone data, ACTH levels showed no diurnal variation during the different Ringer's infusions ( p Ͼ 0.5), although variability during the CT10 experiment was considerably higher than at any other time of the day (16.8 Ϯ 2.8 vs 6.8 Ϯ 1.9, 7.6 Ϯ 2.3, 10.6 Ϯ 1.1, and 11.0 Ϯ 2.4 pg/ml). A number of previous studies have reported diurnal variations in plasma ACTH levels Carnes et al, 1989;Bagdy et al, 1991;Kwak et al, 1992;Ixart et al, 1993), but quite a few others failed to detect significant diurnal variations (Wilkinson et al, 1979;Akana et al, 1986;Carnes et al, 1986;Cascio et al, 1987;Kwak et al, 1993;Suemaru et al, 1995). Important factors that may contribute to the difficulty of finding a circadian ACTH rhythm are the low amplitude of the rhythm, the episodic secretion of ACTH, the sampling protocol used (Carnes et al, 1986;Turek and Van Cauter, 1988;Carnes et al, 1989), and the assay variability (e.g., CT times in different assays).…”

Section: Discussionmentioning

confidence: 99%

A Diurnal Rhythm of Stimulatory Input to the Hypothalamo–Pituitary–Adrenal System as Revealed by Timed Intrahypothalamic Administration of the Vasopressin V₁Antagonist

et al. 1996

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The mammalian suprachiasmatic nuclei (SCN) contain an endogenous pacemaker that generates daily rhythms in behavior and secretion of hormones. We hypothesized that the SCN imposes its circadian rhythm on the rest of the brain via a rhythmic release of its transmitters in its target areas. Previously, we demonstrated a pronounced inhibitory effect of vasopressin (VP), released from SCN terminals in the dorsomedial hypothalamus, on the release of the adrenal hormone corticosterone. In the present study, microdialysis-mediated intracerebral administration of the VP V 1 -receptor antagonist was used to pursue the study of the mechanisms underlying the circadian control of basal corticosterone release. Using timed administrations of the VP antagonist divided equally over the day/night cycle, we were able to uncover the existence of an additional stimulatory input from the SCN to the hypothalamopituitary-adrenal (HPA) axis. Peak activity of this stimulatory SCN input takes place during the second half of the light period, after the daily peak of VP secretion, with a delay of ϳ4 -6 hr. In all likelihood, the inhibitory and stimulatory circadian input via separate mechanisms affects corticosterone release. Together, these two opposing circadian control mechanisms of the HPA axis enable a precise timing of the circadian peak in corticosterone release.

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Episodic secretion of ACTH in rats

Cited by 43 publications

References 34 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

A Diurnal Rhythm of Stimulatory Input to the Hypothalamo–Pituitary–Adrenal System as Revealed by Timed Intrahypothalamic Administration of the Vasopressin V₁Antagonist

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Episodic secretion of ACTH in rats

Cited by 43 publications

References 34 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

A Diurnal Rhythm of Stimulatory Input to the Hypothalamo–Pituitary–Adrenal System as Revealed by Timed Intrahypothalamic Administration of the Vasopressin V1Antagonist

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A Diurnal Rhythm of Stimulatory Input to the Hypothalamo–Pituitary–Adrenal System as Revealed by Timed Intrahypothalamic Administration of the Vasopressin V₁Antagonist