Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice.
Journal of Clinical InvestigationPublished 15 June 1997Open access
Louis J. Muglia, Lauren Jacobson, Stacie Weninger, Christina Luedke, Donald S. Bae, Ki‐Heon Jeong
Citations118
SJR quartileQ1
SJR score4.72
SNIP2.17
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.
Abstract
The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (CRH)-deficient mice generated by homologous recombination in embryonic stem cells. CRH-deficient mice have lost normal circadian variations in plasma ACTH and glucocorticoid while maintaining normal circadian locomotor activity. Constant peripheral infusion of CRH produced marked diurnal excursions of plasma glucocorticoid, indicating that CRH acts in part as a permissive factor for other circadian modulators of adrenocortical activity. The presence of atrophic adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH concentration suggests that the diurnal increase in ACTH is essential to maintain normal adrenal function.
Keywords
MedicineNeuroscience
ScienceCharacterization of a 41-Residue Ovine Hypothalamic Peptide That Stimulates Secretion of Corticotropin and β-Endorphin
3,968 Citations1981Wylie Vale, Joachim Spiess +2 more
Proceedings of the National Academy of SciencesCircadian Rhythms in Drinking Behavior and Locomotor Activity of Rats Are Eliminated by Hypothalamic Lesions
2,015 Citations1972Friedrich K. Stephan, Irving H. Zucker
Bilateral electrolytic lesions in the suprachiasmatic nuclei permanently eliminated nocturnal and circadian rhythms in drinking behavior and locomotor activity of albino rats.
NatureUrocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor
1,493 Citations1995Joan Vaughan, Cynthia J. Donaldson +11 more
This work characterized another mammalian member of the CRF family and localized its urotensin-like immunoreactivity to, and cloned related complementary DNAs from, a discrete rat midbrain region, and deduced a peptide that is related to u Rotensin and CRF, which is named urocortin, which could be an endogenous ligand for type-2 CRF receptors.
ScienceElevated Concentrations of CSF Corticotropin-Releasing Factor-Like Immunoreactivity in Depressed Patients
1,487 Citations1984Charles B. Nemeroff, Erik Widerlöv +7 more
Findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.
Endocrine ReviewsCorticosteroid Inhibition of ACTH Secretion*
1,227 Citations1984Maureen Keller‐Wood, Mary F. Dallman
There is some evidence that suggests that whereas comparator elements are not reset during stress, a comparator element is reset during the course of the circadian rhythm so that different basal levels of steroid are achieved.
Elsevier eBooksRegulation of ACTH Secretion: Variations on a Theme of B
660 Citations1987Mary F. Dallman, Susan F. Akana +4 more
This chapter discusses the regulation of function in the adrenocortical system, which may be activated by traumatic stimuli or by psychological stimuli—in man, examinations, or mental arithmetic, or medical school admissions exams; in rats, unexpected decreases in food rewards.
NatureCorticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need
536 Citations1995Louis J. Muglia, Lauren Jacobson +2 more
It is reported here that corticotropin-releasing hormone-deficient mice reveal a fetal glucocorticoid requirement for lung maturation, suggesting that the major role of glucocORTicoid is during fetal rather than postnatal life.
Journal of Clinical InvestigationModulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.
438 Citations1991Eve Van Cauter, John D Blackman +4 more
The studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by cortisol and growth hormone.
EndocrinologyFood and Water Restriction Shifts Corticosterone, Temperature, Activity and Brain Amine Periodicity
381 Citations1974Dorothy T. Krieger
It is demonstrated that presence of normal light-dark alteration is not sufficient for the maintenance of normal circadian periodicity of plasma corticosteroid levels, and a reversal of AM/PM ratios of hippocampal norepinephrine and of serotonin levels in these animals is demonstrated.
Journal of NeuroscienceCircadian timekeeping in BALB/c and C57BL/6 inbred mouse strains
319 Citations1990WJ Schwartz, P. V. Zimmerman
The results indicate that 1 or more genetic loci influence the value of tauDD, and a large difference in mean tau DD between 2 of the strains, BALB/cByJ and C57BL/6J, allowed further characterization of the origins and inheritance of the polymorphic expression of this circadian pacemaker property.
ScienceSuprachiasmatic Nuclear Lesions Do Not Abolish Food-Shifted Circadian Adrenal and Temperature Rhythmicity
296 Citations1977Dorothy T. Krieger, Herbert Hauser +1 more
Findings suggest the existence of an additional "clock" that may be involved in the generation of the rhythm in animals with lesions of the suprachiasmatic nuclei who are arrhythmic under normal conditions.
Psychological MedicineAdrenal secretion during major depression in 8- to 16-year-olds, I. Altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation
280 Citations1996Ian M. Goodyer, J. Herbert +4 more
Brain ResearchLoss of circadian rhythm in sleep-wakefulness cycle in the rat by suprachiasmatic nucleus lesions
271 Citations1975Nobuo Ibuka, Hiroshi Kawamura
American Journal of Physiology-Endocrinology and MetabolismCircadian modulation of glucose and insulin responses to meals: relationship to cortisol rhythm
238 Citations1992Eve Van Cauter, E Timothy Shapiro +2 more
Time of day did not significantly influence maximum postmeal increment in insulin secretion rate or duration of insulin secretory response, but total and 2-h areas under curve were 25-50% greater in the evening than in the morning.
EndocrinologyAdrenal Sensitivity to Adrenocorticotropin Varies Diurnally*
210 Citations1981Masanori Kaneko, Kuniko Kaneko +2 more
The results together with previous data showing that the magnitude and time course of the adrenal cAMP response to ACTH changes diurnally strongly suggest that ACTH receptor affinity or coupling with adenylate cyclase changesdiurnally.
Journal of EndocrinologyEFFECTS OF LESIONS OF THE SUPRACHIASMATIC NUCLEI AND OF p-CHLOROPHENYLALANINE ON THE CIRCADIAN RHYTHMS OF ADRENOCORTICOTROPHIC HORMONE AND CORTICOSTERONE IN THE PLASMA, AND ON LOCOMOTOR ACTIVITY OF RATS
178 Citations1979A. Szafarczyk, G. Ixart +3 more
The proposition that both the suprachiasmatic nuclei and the serotoninergic system play an irreplaceable role in the mechanism of ACTH secretory rhythms is supported.
EndocrinologyChronic Administration of Corticotropin-Releasing Factor Increases Pituitary Corticotroph Number*
177 Citations1987Barry J. Gertz, Liliana N. Contreras +4 more
The data indicate that long term administration of CRF is capable of increasing the number of pituitary corticotrophs, and supports the view that the corticOTroph hyperplasia occurring after adrenalectomy, in unusual cases of ectopic CRF production, and in rare instances of Cushing's disease is a proliferative response to CRF.
American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyNycthemeral rhythm in adrenal responsiveness to ACTH
171 Citations1978Mary F. Dallman, William C. Engeland +4 more
It is concluded that in vivo measurements of adrenal corticosteroid levels do not necessarily reflect ACTH levels because the rhythms are dissociable and the magnitude of the rhythm in adrenal responsiveness to ACTH is greater than the magnitude in ACTH.
The Journal of Clinical Endocrinology & MetabolismNocturnal Decrease in Glucose Tolerance During Constant Glucose Infusion*
157 Citations1989Eve Van Cauter, Daniel Désir +3 more
In normal subjects the existence of a diurnal variation in glucose tolerance distinct from the dawn phenomenon observed in diabetic subjects is demonstrated and spontaneous 100- to 150-min oscillations in peripheral glucose and insulin levels characterize stimulated pancreatic function, with the amplitude of the oscillations being dependent on the size of the stimulus.
EndocrinologyFeedback sensitivity of the rat hypothalamo-pituitary-adrenal axis and its capacity to adjust to exogenous corticosterone.
156 Citations1992S. F. Akana, Karen A. Scribner +4 more
The HPA axis of intact rats is extremely sensitive to exogenous B and rats with low and middle dose B pellets appeared to adjust HPAaxis function by decreasing the peak diurnal increase in B, so that 24-h mean B levels did not differ from control, and were maintained at approximately 5 micrograms/dl.
American Journal of Physiology-Endocrinology and MetabolismEffects of morning cortisol elevation on insulin secretion and glucose regulation in humans
133 Citations1996Laurence Plat, M. M. Byrne +5 more
Observations support the concept that the 24-h cortisol rhythmicity is responsible, at least in part, for the normal diurnal variation in glucose tolerance.
EndocrinologyMaturation of the Circadian Rhythm of Plasma Corticosterone in the Rat
126 Citations1967CATHERINE F. ALLEN, J. W. Kendall
The data suggest that maturation of the central nervous system’s ability to regulate rhythmic ACTH secretion is delayed well beyond the time when the pituitary is capable of secreting ACTH and the adrenal cortex is able to secrete corticosterone.
EndocrinologyReset of Feedback in the Adrenocortical System: An Apparent Shift in Sensitivity of Adrenocorticotropin to Inhibition by Corticosterone between Morning and Evening*
114 Citations1986Susan F. Akana, Caren S. Cascio +3 more
There is an apparent diurnal change in ACTH sensitivity to corticosterone feedback that can be defined operationally as reset and it is suggested that basal ACTH secretion is maintained in the low normal range in intact rats because of the marked diurnal rhythm in cortic testosterone.
EndocrinologyDiurnal Variations in the Content of Preprocorticotropin-Releasing Hormone Messenger Ribonucleic Acids in the Hypothalamic Paraventricular Nucleus of Rats of Both Sexes as Measured by in Situ Hybridization*
113 Citations1989Alan B. Watts, L. W. Swanson
It is suggested that although the exact mechanism remains to be elucidated, diurnal changes in the rate of CRH synthesis may be involved in the expression of diurnal rhythms within the hypothalamo-hypophysial-adrenal axis.
Journal of Clinical InvestigationExpression of the mouse corticotropin-releasing hormone gene in vivo and targeted inactivation in embryonic stem cells.
113 Citations1994Louis J. Muglia, Nancy A. Jenkins +3 more
Using a highly sensitive reverse transcription-polymerase chain reaction method, expression of CRH mRNA is found in adrenal, ovary, testis, gut, heart, anterior pituitary, lung, and spleen, in addition to cerebral cortex and hypothalamus.
EndocrinologyDifferential expression of corticotropin-releasing hormone in developing mouse embryos and adult brain.
110 Citations1994Catherine E. Keegan, James P. Herman +4 more
The novel findings of CRH expression in fetal lung during the period of glucocorticoid-induced lung maturation and in celiac ganglion during development of the sympathetic nervous system indicate that CRH may have some important developmental functions in addition to its role in activation of the stress response.
Brain ResearchThe suprachiasmatic nuclei stimulate evening ACTH secretion in the rat
107 Citations1987Caren S. Cascio, J. Shinsako +1 more
In rats with B pellets, bilateral lesions of theSCN eliminated the circadian rise in plasma ACTH seen in sham-lesioned animals, consistent with the idea that the SCN stimulate ACTH secretion in the evening.
Journal of Clinical InvestigationContinuous administration of synthetic ovine corticotropin-releasing factor in man. Physiological and pathophysiological implications.
103 Citations1985H. M. Schulte, George P. Chrousos +5 more
The persistent circadian rhythm of ACTH, despite a constant level of plasma CRF during the infusion, suggests that the circadian variation in the activity of the hypothalamic-pituitary-adrenal axis cannot be explained solely by circadian periodicity of the endogenous CRF stimulus.
American Journal of PsychiatryHypothalamic-pituitary-adrenocortical activity and response to cognitive behavior therapy in unmedicated, hospitalized depressed patients
80 Citations1996Michael E. Thase, Sanjay Dubé +5 more
Results are consistent with the hypothesis that patients with increased HPA function are less responsive to psychotherapy and, hence, might require somatic interventions.
NeuroendocrinologyEffects of Alpha-Flupenthixol and Naloxone on CRF-Induced Locomotor Activation
78 Citations2008George F. Koob, Neal R. Swerdlow +5 more
The results suggest that the corticotropin-releasing factor acts independently of direct activation of the dopamine or opioid peptide systems.
EndocrinologyDiurnal variation in resting levels of corticosterone is not mediated by variation in adrenal responsiveness to adrenocorticotropin but involves splanchnic nerve integrity.
72 Citations1996I Dijkstra, Rob Binnekade +1 more
Diurnal variation in adrenal responsiveness to ACTH per se does not exist in this rat model; 2) the strongly acid vehicle interacts with ACTH-induced CORT secretion; 3) the PM rise in plasma CORT depends on the integrity of the sympathetic neural input to the adrenal gland.
NeuroendocrinologyDiurnal CRH mRNA Rhythm in the Hypothalamus: Decreased Expression in the Evening Is Not Dependent on Endogenous Glucocorticoids
63 Citations2008Seung Kwak, María I. Morano +3 more
Results indicate that the endogenous steroid rhythm is not necessary for generating the normal CRH mRNA rhythm during the light phase, and a constant exposure to corticosterone at approximately 50% of the daily mean appears to be sufficient for regulation of the mRNA rhythm.
The Journal of Clinical Endocrinology & MetabolismPituitary-Adrenal Responsiveness to Corticotropin-Releasing Hormone in Patients Receiving Chronic, Alternate Day Glucocorticoid Therapy*
54 Citations1985Thomas H. Schürmeyer, George C. Tsokos +5 more
The data suggest that the blunting of responsiveness to oCRH on both days of testing represents prednisolone suppression of the corticotroph cell, suggesting that moderate decreases in daily ACTH secretion are compatible with sustaining normal adrenal function.
EndocrinologyProtein Malnutrition Increases Plasma Adrenocorticotropin and Anterior Pituitary Proopiomelanocortin Messenger Ribonucleic Acid in the Rat*
54 Citations1997Lauren Jacobson, David Zurakowski +1 more
It is concluded that protein malnutrition increases pituitary-adrenocortical activity at least in part by specifically increasing the drive for ACTH synthesis and secretion.
EndocrinologyDevelopment of the Circadian Adrenocortical Rhythm in Rats: Studied by Determination of 24- or 48-Hour Patterns of Blood Corticosterone Levels in Individual Pups*
47 Citations1979Kiyohisa Takahashi, Koichi Hanada +4 more
Time sequence analysis revealed that the circadian adrenocortical rhythm was established at this age, and well nurtured pups tended to develop the rhythm earlier than poorly nurtured ones.
Physiology & BehaviorEffects of adrenal steroid agonists on food intake and macronutrient selection
46 Citations1992Donna L. Tempel, Bruce S. McEwen +1 more
Results indicate that CORT and the selective type II receptor agonist RU28362 specifically stimulate carbohydrate ingestion after SC or PVN administration, while DEX has no effect on feeding.
EndocrinologyDifferential expression of corticotropin-releasing hormone in developing mouse embryos and adult brain
46 Citations1994C. E. Keegan
EndocrinologyEffects of Immunoneutralization of Corticotropin-Releasing Hormone on Ultradian Rhythms of Plasma Adrenocorticotropin*
44 Citations1990Molly Carnes, Stephanie J. Lent +4 more
This is the first in vivo evidence of pulsatile ACTH secretion independent of CRH, the first report demonstrating that different ultradian rhythms of ACTH may be regulated by different mechanisms, and the first comparison of PULSAR and Cluster Analysis on plasma ACTH time series.
Behavior GeneticsCircadian period in mice: Analysis of genetic and maternal contributions to inbred strain differences
41 Citations1988Bernard Possidente, Friedrich K. Stephan
Results indicate that the inbred strain differences in circadian period are imposed primarily by direct effects of allelic differences among the strains, rather than through maternally mediated mechanisms.
Advances in experimental medicine and biologyCircadian Pituitary Adrenal Rhythms
31 Citations1975Dorothy T. Krieger
The present report will attempt to define the characteristics of circadian periodicity of plasma corticosteroid levels and describe experimental approaches, both in animals and humans, which have been designed to delineate the factors underlying this periodicity.
Journal of NeuroendocrinologyCircadian Rhythms: Peering into the Molecular Clockwork
27 Citations1995Michael H. Hastings
The lid is being opened on one of the classic 'black boxes' of biology, the circadian clock, with new developments in the understanding of the molecular basis of circadian rhythms.
NeuroendocrinologyCircadian Patterns of Plasma Immunoreactive Corticotropin, Beta-Endorphin, Corticosterone and Prolactin after Immunoneutralization of Corticotropin-Releasing Hormone
24 Citations2008György Bagdy, George P. Chrousos +1 more
CRH immunoneutralization caused no significant decreases in circulating immunoreactive ACTH, beta-END and corticosterone plasma levels at noon, but abolished the evening rises of these hormones, and PRL levels were not significantly different between the groups at any time point measured.
Pediatric Clinics of North AmericaThe Cushing Syndromes
22 Citations1990Kenneth L. Jones
Improved assays of ACTH and the availability of CRF have provided new insight into the physiology and pathophysiology of the HPA axis and new tools for diagnosis of CS, especially in combination with selective catheterization and sampling.
Brain ResearchThe paraventricular nucleus is uniquely responsive to the feeding stimulatory effects of steroid hormones
22 Citations1993Donna L. Tempel, Taewan Kim +1 more
Results identify the hypothalamic paraventricular nucleus, and the steroid receptors located within it, as having a specific function in mediating the action of CORT and ALDO on carbohydrate and fat intake, respectively.
EndocrinologyProtein Malnutrition Increases Plasma Adrenocorticotropin and Anterior Pituitary Proopiomelanocortin Messenger Ribonucleic Acid in the Rat
19 Citations1997Lauren Jacobson
Biological PsychiatryDiurnal neuroendocrine and autonomic function in acute and remitted depressed male patients
15 Citations1995Robert L. Trestman, Rachel Yehuda +5 more
Diurnal data lend limited support to the dysregulation hypotheses of depression that suggest normal circadian rhythmicities are altered or disrupted in acute depression and that peripheral manifestations of central dysregulation normalize in remission of depression.