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

Spiga, Francesca; Walker, Jamie J.; Gupta, Rita R.; Terry, John R.; Lightman, Stafford L.

doi:10.1530/joe-15-0132

Cited by 42 publications

(29 citation statements)

References 87 publications

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“…These low ultradian increases in ACTH appear to function through direct effects of PKA on the basal level of StAR mRNA through the rapid translation-dependent process shown in figure 1 that involves mitochondrial import and IMM metalloprotease cleavage. This process has been shown to provide a cholesterol transfer cycle in Y-1 cells of about 5 minutes, which is fully compatible with the modeling carried out for ultradian responses (Spiga et al, 2015). The rapid modulation provided by processing of the NTD can play a role in synchronizing ACTH fluctuations with mitochondrial cholesterol transfer and with changes in the cytoplasmic availability of cholesterol.…”

Section: Star Responses To Episodic In Vivo Acth Signalingsupporting

confidence: 82%

“…The rapid NTD modulation of CBD activity effectively uncouples ultradian pulses from the much slower diurnal regulation derived from the hypothalamus both through the autonomic stimulation of the adrenal medulla and from ACTH pulse variation. These diurnal changes closely correlate with changes in adrenal transcription factors (Spiga et al, 2015). …”

Section: Star Responses To Episodic In Vivo Acth Signalingmentioning

confidence: 83%

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A single cell level measurement of StAR expression and activity in adrenal cells

Lee

Yamazaki

Dong

et al. 2017

Molecular and Cellular Endocrinology

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The Steroidogenic acute regulatory protein (StAR) directs mitochondrial cholesterol uptake through a C-terminal cholesterol binding domain (CBD) and a 62 amino acid N-terminal regulatory domain (NTD) that contains an import sequence and conserved sites for inner membrane metalloproteases. Deletion of the NTD prevents mitochondrial import while maintaining steroidogenesis but with compromised cholesterol homeostasis. The rapid StAR-mediated cholesterol transfer in adrenal cells depends on concerted mRNA translation, p37 StAR phosphorylation and controlled NTD cleavage. The NTD controls this process with two cAMP-inducible modulators of, respectively, transcription and translation SIK1 and TIS11b/Znf36l1. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA resolves slow RNA splicing at the gene loci in cAMP-induced Y-1 cells and transfer of individual 3.5 kb mRNA molecules to mitochondria. StAR transcription depends on the CREB coactivator CRTC2 and PKA inhibition of the highly inducible suppressor kinase SIK1 and a basal counterpart SIK2. PKA-inducible TIS11b/Znf36l1 binds specifically to highly conserved elements in exon 7 thereby suppressing formation of mRNA and subsequent translation. Co-expression of SIK1, Znf36l1 with 3.5 kb StAR mRNA may limit responses to pulsatile signaling by ACTH while regulating the transition to more prolonged stress

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Section: Star Responses To Episodic In Vivo Acth Signalingsupporting

confidence: 82%

Section: Star Responses To Episodic In Vivo Acth Signalingmentioning

confidence: 83%

A single cell level measurement of StAR expression and activity in adrenal cells

Lee

Yamazaki

Dong

et al. 2017

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

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“…At first glance, this decrease in corticosterone is contrary to the concept of stress research because evidence predominately indicates an increase in corticosterone levels as a physiological response to stress (King and Hegadoren, 2002; Brush, 2003; Steimer and Driscoll, 2003; Lightman, 2008; Ganella and Kim, 2014; Spiga et al, 2015). …”

Section: Discussionmentioning

confidence: 90%

A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems

Oliveira

Gouveia

Castro

et al. 2016

Front. Behav. Neurosci.

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The avoidance response is present in pathological anxiety and interferes with normal daily functions. The aim of this article is to shed light on performance markers of active avoidance (AA) using two different rat strains, Sprague-Dawley (SD) and Wistar. Specifically, good and poor performers were evaluated regarding anxiety traits exhibited in the elevated plus maze (EPM) and corticosterone levels and motor activity in the open field test. In addition, the plasma levels of Interleukin-6 (IL-6), Interleukin-1Beta (IL-1beta), Nerve Growth Factor Beta (NGF-beta), Tumor Necrosis Factor-Alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were compared in the good and poor performers to better understand the role of the immunologic system in aversive learning. Behavioral criteria were employed to identify subpopulations of SD and Wistar rats based on their behavioral scores during a two-way AA test. The animals were tested for anxiety-like behavior in the EPM and motor activity in the open-field test. Plasma corticosterone levels were measured at the end of the avoidance test. Cytokine levels of IL-6, IL-1beta, NGF-beta, TNF-alpha, and CINC-1 were measured in the plasma of the Wistar rats. Sixty-six percent of the Wistar rats and 35% of the SD rats exhibited a poor performance. This feature was associated with a decrease in anxiety-like behavior in the EPM. The poor and good performers exhibited lower levels of corticosterone compared with the control animals, which suggests that training alters corticosterone levels, thereby leading to hypocortisolism, independent of the performance. The CINC-1 levels were increased in the poor performers, which reinforces the role of immunologic system activation in learning deficits. Our study provides a better understanding of the complex interactions that underlie neuroimmune consequences and their implications for performance.

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“…Since others did not find any difference over 24 h of urine collection (15), these findings in children and in the present animal study underline the need to take into account the phase of the nycthemeral cycle in which HPA axis activity is studied. Functionally, increased corticosterone levels at time of secretion nadir results in a globally flattened circadian secretion of the hormone that is known to have deleterious consequences on the body as well as on the brain (16). Of note, hippocampal 11β-HSD1 activity was also found elevated in diabetic untreated animals.…”

Section: Discussionmentioning

confidence: 99%

Diabetes and Insulin Injection Modalities: Effects on Hepatic and Hippocampal Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Juvenile Diabetic Male Rats

et al. 2017

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BackgroundDysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is often encountered in diabetes, leading to several clinical complications. Our recent results showing an elevated tetrahydrocortisol/tetrahydrocorticosterone ratio in morning urine of diabetic children compared to that of controls suggest an increased nocturnal activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the former.QuestionWe hypothesized that these observations could be explained by a reduced inhibition of hepatic 11β-HSD1 activity by exogenous insulin owing to its subcutaneous (SC) administration and absence of first hepatic passage. Additionally, we hypothesized that hippocampal 11β-HSD1 activity might also be impaired by diabetes.MethodsWe therefore measured HPA axis activity and 11β-HSD1 expression and activity in liver and hippocampus in streptozotocin-induced diabetic juvenile rats treated with SC or intraperitoneal (IP) insulin.ResultsPlasma corticosterone levels were elevated in untreated diabetic rats during the resting phase and restored by both types of insulin treatment. The mRNA expression and activity of 11β-HSD1 were increased in the untreated diabetic group in liver. Although diabetes was controlled equally whatever the route of insulin administration, liver 11β-HSD1 gene expression and activity was decreased only in the IP group, suggesting that a first hepatic pass is needed for 11β-HSD1 hepatic inhibition. In hippocampus, 11β-HSD1 activity was elevated in the untreated diabetic group but restored by both types of insulin treatment. Thus, these data extend our findings in diabetic children by showing impairment of hippocampal 11β-HSD1 in diabetes and by demonstrating that IP is preferable to SC insulin administration to restore 11β-HSD1 activity in liver.

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

Cited by 42 publications

References 87 publications

A single cell level measurement of StAR expression and activity in adrenal cells

A single cell level measurement of StAR expression and activity in adrenal cells

A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems

Diabetes and Insulin Injection Modalities: Effects on Hepatic and Hippocampal Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Juvenile Diabetic Male Rats

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