Pulsatile ACTH secretion: Variation with time of day and relationship to cortisol

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

doi:10.1016/0196-9781(88)90268-9

Cited by 57 publications

(25 citation statements)

References 33 publications

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“…In response to a stressor of mock capture, morning cortisol values for M. fascicularis rose from 30 μg/dl to 46 μg/dl [27]. ACTH values in the present study averaged 63 pg/mg, compared with morning values of 47-56 pg/ml for male M. mulatta [7] and afternoon values of 15-32 pg/ml for male M. mulatta [6]. In female macaques (M. mulatta, M. fascicularis, M. radiata), plasma ACTH and cortisol levels rose significantly after exposure to acute stressors (awake venipuncture, hand-capture, transport, telemetry jacket); values (average of morning and afternoon) were ∼40 pg/ml baseline and ∼67 pg/ml stressed for ACTH, and ∼27 μg/dl baseline and 50 μg/dl stressed for cortisol [8].…”

Section: Acth Cortisol and Dysregulation Indexcontrasting

confidence: 54%

“…However, opioid levels can also be influenced by these factors, yet significant BET, BEC, and BEN effects were found. In macaques, both ACTH and cortisol vary with time of day, being higher in the morning [7]. The plasma cortisol values in the present study averaged 38 μg/dl, compared with baseline morning values of 27 μg/dl from M. mulatta [2,5] and ∼23 μg/dl from M. fascicularis [10].…”

Section: Acth Cortisol and Dysregulation Indexcontrasting

confidence: 51%

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Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

et al. 2007

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Frequent or severe abnormal behavior may be associated with the release of endorphins that positively reinforce the behavior with an opiate euphoria or analgesia. One line of research exploring this association involves the superhormone, proopiomelanocortin (POMC). The products of POMC appear to be dysregulated in some human subjects who exhibit self-injurious behavior (SIB). Macaque monkeys have POMC very similar to humans, and some laboratory macaques display SIB or frequent stereotypies. We investigated associations between plasma levels of three immunoreactive POMC fragments with possible opioid action and abnormal behavior ratings in macaques. In 58 adult male and female macaques (24 Macaca fascicularis and 34 M. nemestrina), plasma levels of intact beta-endorphin (βE) and the N-terminal fragment (BEN) were significantly higher in animals with higher levels of abnormal behavior. The C-terminal fragment (BEC) was significantly higher in males but unrelated to ratings of abnormal behavior. Levels of ACTH, cortisol, and (βE-ACTH)/βE dysregulation index were unrelated to abnormal behavior. None of the POMC products differed significantly by subjects' species, age, or weight. The finding that intact betaendorphin is positively related to abnormal behavior in two species of macaque is consistent with some previous research on human subjects and nonprimates. The positive relation of the N-terminal fragment of βE to abnormal behavior is a new finding.

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Section: Acth Cortisol and Dysregulation Indexcontrasting

confidence: 54%

Section: Acth Cortisol and Dysregulation Indexcontrasting

confidence: 51%

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

et al. 2007

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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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“…The prominent diurnal peak in circulating levels of adrenal steroids before the onset of the daily period of increased activity has been described in numerous species, including rats (Guillemin et al, 1959;McCarthy et al, 1960), monkeys (Perlow et al, 1981;Carnes et al, 1988), domestic animals (Lincoln et al, 1982;Klemcke et al, 1989;Lefcourt et al, 1993;Irvine and Alexander, 1994), and humans (Van Cauter, 1990;Linkowski et al, 1993). In diurnal species such as the human and the pig, plasma glucocorticoid levels are high in the early morning and then decline, reaching a nadir in the evening.…”

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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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Pulsatile ACTH secretion: Variation with time of day and relationship to cortisol

Cited by 57 publications

References 33 publications

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

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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Pulsatile ACTH secretion: Variation with time of day and relationship to cortisol

Cited by 57 publications

References 33 publications

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

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