Interleukin-1-induced corticosterone release occurs by an adrenergic mechanism from rat adrenal gland

Interleukin-1 (IL-1) has been shown to stimulate corticosterone release from the adrenal gland directly, and indirectly through activation of the hypothalamic-pituitary-adrenal axis. The aim of this paper was to determine whether IL-1-stimulated corticosterone release occurs indirectly through the local release of catecholamines from the rat adrenal gland. To accomplish this, experiments were conducted on both quartered rat adrenal glands and primary cultures of dispersed adrenal cells. Incubation of quartered adrenals with adrenocorticotropic hormone (ACTH, 10(-12) to 10(-8) M) or IL-1 beta (10(-12) to 10(-8) M) resulted in dose-dependent increases (P less than 0.05) in corticosterone release. Corticosterone release stimulated by 10(-8) M doses of ACTH and IL-1 beta began to rise 30 min after incubation and peaked at 2 h. In primary cultures of adrenal cells, IL-1 alpha and IL-1 beta elevated corticosterone release after a 24-h incubation period. ACTH elevated corticosterone levels at 4 and 24 h. The stimulatory effect of IL-1 on corticosterone release was mimicked by epinephrine (10(-6) M), and was selectively blocked by the alpha-adrenergic antagonist phentolamine (10(-5) M). The beta-adrenergic antagonist propranolol (10(-5) M) did not change IL-1-induced corticosterone release. Neither phentolamine nor propranolol had an effect on ACTH-stimulated corticosterone release. Both IL-1 alpha and IL-1 beta significantly increased (P less than 0.05) epinephrine levels after a 24-h incubation period compared with media-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Adrenal Cell Aldosterone Production Is Stimulated by Very-Low-Density Lipoprotein (VLDL)

Endocrinology ◽

10.1210/en.2011-1752 ◽

2012 ◽

Vol 153 (2) ◽

pp. 721-731 ◽

Cited By ~ 21

Author(s):

Yewei Xing ◽

William E. Rainey ◽

John W. Apolzan ◽

Omar L. Francone ◽

Ruth B. S. Harris ◽

...

Keyword(s):

Adrenal Gland ◽

Primary Cultures ◽

Signal Transduction Pathway ◽

Free Calcium ◽

Low Density ◽

Dependent Manner ◽

Very Low Density Lipoproteins ◽

Concentration Dependent Manner ◽

Adrenal Cells

Very low-density lipoproteins (VLDL) are a class of large lipoprotein synthesized in the liver. The key function of VLDL, in vivo, is to carry triglyceride from the liver to adipose tissue. As a steroidogenic organ, the adrenal gland mainly uses lipoproteins as sources of cholesterol. Although VLDL receptors have been detected in the human adrenal, the function of VLDL in the adrenal gland remains unknown. Herein, we used primary cultures of human and bovine adrenal cells and the adrenocortical cell line H295R as models to determine the effects of VLDL on adrenal steroidogenesis. Our studies revealed that VLDL significantly increased aldosterone synthesis in all of the models tested. This increase was largely due to VLDL's stimulation of the expression of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2). VLDL increased CYP11B2 mRNA expression in a concentration-dependent manner. Effects of VLDL on CYP11B2 transcript levels were not additive with angiotensin II or potassium but were additive with the cAMP pathway agonists ACTH and forskolin. Nifedipine completely inhibited the effects of VLDL on CYP11B2 mRNA, suggesting that calcium is the main signal transduction pathway used by VLDL in adrenal cells. Indeed, VLDL increased cytosolic free calcium levels. An in vivo study conducted in sucrose-fed rats showed a positive correlation between elevated triglyceride (VLDL) levels in plasma and CYP11B2 expression in the adrenal. In conclusion, we have shown that VLDL can stimulate aldosterone synthesis in adrenocortical cells by increasing StAR and CYP11B2 expression, an event likely mediated by a calcium-initiated signaling cascade.

Download Full-text

EVIDENCE FOR THE SECRETION OF INHIBIN-LIKE IMMUNOREACTIVITY FROM CULTURED HUMAN ADRENAL CELLS

Journal of Endocrinology ◽

10.1677/joe.0.128r013 ◽

1991 ◽

Vol 128 (3) ◽

pp. R13-R16 ◽

Cited By ~ 10

Author(s):

M. Haji ◽

Y. Nishi ◽

S. Tanaka ◽

M. Ohashi ◽

K. Sekiya ◽

...

Keyword(s):

Adrenal Gland ◽

Adrenal Glands ◽

Displacement Curve ◽

Dependent Manner ◽

Adrenal Cells ◽

Gland Extract ◽

Wet Weight ◽

Dose Dependent

ABSTRACT We have studied the production and release of inhibin-like immunoreactivity in the human adrenal gland. Extract of human adrenal glands showed a displacement curve paralled with the inhibin standard. Inhibin-like immunoreactivity contents in the adrenal gland was 1893±474 (mean±S.D.) IU/g wet weight tissue. ACTH stimulated the secretion of inhibin-like immunoreactivity as well as cortisol and aldosterone in a dose-dependent manner in the cultured adrenal cells. These results indicate that the human adrenal gland produces and secretes inhibin-like peptide in response to ACTH.

Download Full-text

Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.4.r855 ◽

2000 ◽

Vol 278 (4) ◽

pp. R855-R862 ◽

Cited By ~ 6

Author(s):

Jane M. Daun ◽

Richard W. Ball ◽

Joseph G. Cannon

Keyword(s):

Mononuclear Cells ◽

Interleukin 1 ◽

Dependent Manner ◽

Basal Secretion ◽

Peripheral Blood Mononuclear ◽

Age Related ◽

Agonist And Antagonist ◽

And Gender ◽

Dose Dependent ◽

Pituitary Adrenal Axis

Interleukin-1 (IL-1) is a primary mediator of inflammation that is regulated, in part, by the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine if gender- or age-related differences exist in the sensitivity of IL-1-producing cells to hydrocortisone. Peripheral blood mononuclear cells (PBMC) isolated from men and women (21–77 yr old) were incubated with hydrocortisone (0, 50, 100, 500, or 1,000 ng/ml) with or without lipopolysaccharide (LPS). Secretion of IL-1β and IL-1 receptor antagonist was inhibited in a dose-dependent manner ( P = 0.001) without age- or gender-related differences. Hydrocortisone decreased soluble IL-1 receptor type II (sIL-1RII) secretion by unstimulated cells ( P = 0.0001), but it increased secretion by LPS-stimulated cells ( P = 0.0001) in all groups. Unstimulated cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women ( P= 0.011). Compared with men, PBMCs from women were less responsive to hydrocortisone inhibition of sIL-1RII secretion, regardless of age ( P = 0.001), and compared with the follicular phase, sIL-1RII secretion was lower in the luteal phase of the menstrual cycle ( P < 0.05). These data indicate that basal secretion and glucocorticoid modulation of sIL-1RII secretion by cultured PBMCs are gender dependent. Moreover, glucocorticoid influences on sIL-1RII secretion depend on the presence or absence of gram-negative bacterial toxins.

Download Full-text

Synergism between IL-1 beta and TNF-alpha on the activity of the pituitary-adrenal axis and on food intake of rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.4.e551 ◽

1995 ◽

Vol 268 (4) ◽

pp. E551-E557 ◽

Cited By ~ 3

Author(s):

M. J. Van der Meer ◽

C. G. Sweep ◽

G. J. Pesman ◽

G. F. Borm ◽

A. R. Hermus

Keyword(s):

Food Intake ◽

Rectal Temperature ◽

Interleukin 1 ◽

Intraperitoneal Administration ◽

Human Tumor ◽

Adrenal Weight ◽

Necrosis Factor Alpha ◽

Adrenal Axis ◽

Dose Dependent ◽

Pituitary Adrenal Axis

We investigated the effects of separate and combined intraperitoneal administration for 3 days of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor-alpha (TNF) on plasma adrenocorticotropic hormone (ACTH) and corticosterone (B) levels, adrenal weight, food intake, and rectal temperature. Rats were equipped with a jugular cannula for daily blood sampling and with an intraperitoneally implanted Alzet osmotic minipump loaded with either saline, IL-1 (2.0 micrograms/day), TNF (0.2, 2.0, or 10.0 micrograms/day), or IL-1 in combination with TNF. Plasma ACTH and B levels and adrenal weight were significantly increased, in a dose-dependent way, by simultaneous infusion of IL-1 and TNF but not by administration of either cytokine alone. Chronic administration of IL-1 alone induced a significant decrease in food intake and a significant elevation of rectal temperature, whereas infusion of only the highest dose of TNF significantly elevated rectal temperature. Coinfusion of IL-1 and TNF induced both effects in a dose-dependent and synergistic way. Our data show that simultaneous infusion of IL-1 and TNF in rats has a synergistic effect on the activity of the pituitary-adrenal axis as well as on food intake and rectal temperature. The existence of two pathways, which act synergistically, may increase the sensitivity of the host to respond to subtle inflammatory stimuli.

Download Full-text

Contribution of Growth Arrest-Specific 5/miR-674 to the Hypothalamus Pituitary Adrenal Axis Regulation Effect by Electroacupuncture following Trauma

NeuroImmunoModulation ◽

10.1159/000513385 ◽

2021 ◽

pp. 1-13

Author(s):

Jing Zhu ◽

Chunxia Guo ◽

Pingping Lu ◽

Shuijin Shao ◽

Bing Tu

Keyword(s):

Hpa Axis ◽

Interleukin 1 ◽

Growth Arrest ◽

Luciferase Assay ◽

Function Evaluation ◽

Protein Levels ◽

Adrenal Axis ◽

Post Surgery ◽

Hypothalamus Pituitary Adrenal Axis ◽

Pituitary Adrenal Axis

Background: Electroacupuncture (EA) can improve trauma-induced hypothalamus pituitary adrenal axis (HPA) hyperactivity. However, the mechanism underlying the EA effect has not been fully understood. Methods and Study Design: This study was undertaken to explore the role of hypothalamic growth arrest-specific 5 (Gas5) in the regulation of EA on HPA axis function post-surgery. Paraventricular nuclear Gas5 levels were upregulated in rats using an intracerebroventricular injection of pAAV-Gas5. Primary hypothalamic neurons and 293T cells were cultured for miRNA and siRNAs detection. Radioimmunoassay, PCR, Western blot, and immunohistochemistry were used for HPA axis function evaluation. Results: The overexpression of Gas5 abolished the effect of EA on the regulation of trauma-induced HPA axis hyperactivity. Using a bioinformatics analysis and dual luciferase assay, we determined that miRNA-674 was a target of Gas5. Additionally, miRNA-674 levels were found to have decreased in trauma rats, and this effect was reversed after EA intervention. TargetScan analysis showed that serum and glucocorticoid inducible kinase 1 (SGK1) were targets of miR-674. Moreover, we found that SGK1 protein levels increased in trauma rats and SGK1 expression inhibition alleviated HPA axis abnormality post-surgery. EA could improve the number of hypothalamus iba-1 positive cells and hypothalamic interleukin 1 beta protein expression. Conclusions: Our study demonstrated the involvement of the hypothalamic Gas5/miRNA-674/SGK1 signaling pathway in EA regulation of HPA axis function after trauma.

Download Full-text

Vasoactive Effects of Acute Ergot Exposure in Sheep

Toxins ◽

10.3390/toxins13040291 ◽

2021 ◽

Vol 13 (4) ◽

pp. 291

Author(s):

Rossalin Yonpiam ◽

Jair Gobbet ◽

Ashok Jadhav ◽

Kaushik Desai ◽

Barry Blakley ◽

...

Keyword(s):

Single Dose ◽

Chronic Exposure ◽

Contractile Response ◽

Ergot Alkaloids ◽

Acute Exposure ◽

Control Group ◽

Vascular Effects ◽

Adrenergic Antagonist ◽

Vascular Sensitivity ◽

Dose Dependent

Ergotism is a common and increasing problem in Saskatchewan’s livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects of a single oral dose with high-level exposure to ergot alkaloids remain unknown and are examined in this study. This study had two main objectives; the first was to evaluate the role of α1-adrenergic receptors in mediating the acute vasocontractile response after single-dose exposure in sheep. The second was to examine whether terazosin (TE) could abolish the vascular contractile effects of ergot alkaloids. Twelve adult female sheep were randomly placed into control and exposure groups (n = 6/group). Ergot sclerotia were collected and finely ground. The concentrations of six ergot alkaloids (ergocornine, ergocristine, ergocryptine, ergometrine, ergosine, and ergotamine) were determined using HPLC/MS at Prairie Diagnostic Services Inc., (Saskatoon, SK, Canada). Each ewe within the treatment group received a single oral treatment of ground ergot sclerotia at a dose of 600 µg/kg BW (total ergot) while each ewe in the control group received water. Animals were euthanized 12 h after the treatment, and the pedal artery (dorsal metatarsal III artery) from the left hind limb from each animal was carefully dissected and mounted in an isolated tissue bath. The vascular contractile response to phenylephrine (PE) (α1-adrenergic agonist) was compared between the two groups before and after TE (α1-adrenergic antagonist) treatment. Acute exposure to ergot alkaloids resulted in a 38% increase in vascular sensitivity to PE compared to control (Ctl EC50 = 1.74 × 10−6 M; Exp EC50 = 1.079 × 10−6 M, p = 0.046). TE treatment resulted in a significant dose-dependent increase in EC50 in both exposure and control groups (p < 0.05 for all treatments). Surprisingly, TE effect was significantly more pronounced in the ergot exposed group compared to the control group at two of the three concentrations of TE (TE 30 nM, p = 0.36; TE 100 nM, p < 0.001; TE 300 nM, p < 0.001). Similar to chronic exposure, acute exposure to ergot alkaloids results in increased vascular sensitivity to PE. TE is a more potent dose-dependent antagonist for the PE contractile response in sheep exposed to ergot compared to the control group. This study may indicate that the dry gangrene seen in sheep, and likely other species, might be related to the activation of α1-adrenergic receptor. This effect may be reversed using TE, especially at early stages of the disease before cell death occurs. This study may also indicate that acute-single dose exposure scenario may be useful in the study of vascular effects of ergot alkaloids.

Download Full-text

μ-Opiate Receptors in Neuronal Primary Cultures from Cerebral Cortex

Alternatives to Laboratory Animals ◽

10.1177/026119299001700308 ◽

1990 ◽

Vol 17 (3) ◽

pp. 177-181

Author(s):

Peter S. Eriksson ◽

Elisabeth Hansson ◽

Lars Rönnbäck

Keyword(s):

Cerebral Cortex ◽

Primary Cultures ◽

Opiate Receptors ◽

Neuronal Cultures ◽

Camp Accumulation ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Neuronal Primary Cultures ◽

Dose Dependent ◽

Μ Receptor

The presence of μ-opioid receptors was demonstrated as effects of receptor stimulation on PGE1-induced cAMP accumulation in neuronal-enriched primary cultures from rat cerebral cortex. Morphine was used as a μ-receptor agonist. There was a dose-dependent inhibition of the PGE1-stimulated cAMP accumulation by morphine, blocked by the μ-receptor antagonist naloxone. These findings suggest that these neuronal cultures express μ-receptors, possibly connected to adenylate cyclase via an inhibitory Gi-protein. The probable use of functional μ-receptors in neurotoxicological tests is discussed.

Download Full-text

Interleukin-8 Synthesis, Regulation, and Steroidogenic Role in H295R Human Adrenocortical Cells

Endocrinology ◽

10.1210/en.2005-0951 ◽

2006 ◽

Vol 147 (2) ◽

pp. 891-898 ◽

Cited By ~ 22

Author(s):

Damian G. Romero ◽

Gaston R. Vergara ◽

Zheng Zhu ◽

Gina S. Covington ◽

Maria W. Plonczynski ◽

...

Keyword(s):

Immune System ◽

Angiotensin Ii ◽

Adrenal Gland ◽

Interferon Γ ◽

Cell Culture Supernatant ◽

Adrenocortical Cells ◽

Adrenal Cells ◽

Endothelin 1 ◽

H295r Cells ◽

First Time

The adrenal gland secretes several cytokines, and cytokines modulate steroid secretion by this gland. In this study, a survey of cytokine production by H295R human adrenocortical cells demonstrated that these cells secreted IL-2, IL-4, IL-8, IL-10, IL-13, and TNFα but not IL-5, IL-12, or interferon-γ. IL-8 was the IL secreted at higher concentration. IL-8 secretion, its regulation, and role in steroidogenesis were further studied. Secreted ILs and steroids were measured by ELISA in cell culture supernatant. IL-8 mRNA was quantified by real-time RT-PCR. H295R cells and human adrenal gland expressed IL-8 mRNA. Angiotensin II, potassium, endothelin-1, IL-1α, IL-1β, TNFα, and Escherichia coli lipopolysaccharide dose-dependently increase IL-8 secretion by H295R cells after 24 h incubation. IL-6 had no effect on IL-8 secretion. Angiotensin II time-dependently increased IL-8 secretion by H295R cells up to 48 h. Angiotensin II caused a biphasic increase in IL-8 mRNA expression with a peak 6 h after stimulation. TNFα synergized angiotensin II, potassium, and IL-1α-mediated IL-8 secretion. IL-8 did not modify aldosterone or cortisol secretion by H295R cells under basal or stimulated (angiotensin II or potassium) conditions. In conclusion, it is demonstrated for the first time that human adrenal cells expressed and secreted IL-8 under the regulation of angiotensin II, potassium, endothelin-1, and immune peptides. Adrenal-secreted IL-8 is one point of convergence between the adrenal gland and the immune system and may have relevance in physiological and pathophysiological conditions associated with increased levels of aldosterone secretagogues and the immune system.

Download Full-text

Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor.

Journal of Experimental Medicine ◽

10.1084/jem.175.4.1139 ◽

1992 ◽

Vol 175 (4) ◽

pp. 1139-1142 ◽

Cited By ~ 30

Author(s):

H R Alexander ◽

G G Wong ◽

G M Doherty ◽

D J Venzon ◽

D L Fraker ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Leukemia Inhibitory Factor ◽

Tumor Necrosis ◽

Interleukin 1 ◽

Inhibitory Factor ◽

Dependent Manner ◽

Lps Challenge ◽

Differentiation Factor ◽

Dose Dependent ◽

Necrosis Factor

Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose-dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge.

Download Full-text

Regulation of rabbit acute phase protein biosynthesis by monokines

Biochemical Journal ◽

10.1042/bj2530851 ◽

1988 ◽

Vol 253 (3) ◽

pp. 851-857 ◽

Cited By ~ 61

Author(s):

A Mackiewicz ◽

M K Ganapathi ◽

D Schultz ◽

D Samols ◽

J Reese ◽

...

Keyword(s):

Acute Phase ◽

Serum Amyloid A ◽

Interleukin 1 ◽

Serum Amyloid ◽

C Reactive Protein ◽

Reactive Protein ◽

Amyloid A ◽

Primary Hepatocyte Cultures ◽

Dose Dependent ◽

Necrosis Factor

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.

Download Full-text