Lipopolysaccharide is able to bypass corticotrophin-releasing factor in affecting plasma ACTH and corticosterone levels: evidence from rats with lesions of the paraventricular nucleus

ABSTRACT Stimulation of the immune system or experimental conditions (bacterial lipopolysaccharide (LPS) treatment) provoke a broad spectrum of physiological responses. It was recently shown that one of them is the activation of the hypothalamic-pituitary-adrenal (HPA) axis. The mechanism and the site or sites through which LPS stimulates the HPA axis are not well understood. To establish whether the effect of bacterial LPS is related in vivo to the presence of hypothalamic hypophysiotrophic peptides (corticotrophin-releasing factor-41, arginine vasopressin, etc.), plasma ACTH and corticosterone levels were monitored in intact and sham-operated rats, and in rats with paraventricular nucleus lesions in order to remove the main source of these neuropeptides. Evidence was obtained that 4 h after treatment, LPS was able to activate the hypophysial-adrenal system in the absence of hypophysiotrophic neuropeptides of paraventricular origin. It is suggested that, in vivo, LPS could have a direct effect on the pituitary gland or that it acts through an extrapituitary, non-paraventricular pathway to activate the HPA axis. Journal of Endocrinology (1992) 133, 231–236

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CORTICOID PRODUCTION IN VITRO AS A TEST OF ADRENOCORTICAL FUNCTION IN RATS

Acta Endocrinologica ◽

10.1530/acta.0.xxxiii0059 ◽

1960 ◽

Vol XXXIII (I) ◽

pp. 59-66 ◽

Cited By ~ 15

Author(s):

J. van der Vies

Keyword(s):

Adrenal Cortex ◽

Adrenal Function ◽

The Other ◽

Adrenocortical Function ◽

Experimental Conditions ◽

Adrenal System ◽

Other Hand ◽

Stimulation Of

ABSTRACT Adrenal function in rats under various experimental conditions was studied by incubating the adrenals in vitro and determining the corticosteroid output during one hour. This in vitro corticoid production was reduced after hypophysectomy, hypothalamus-lesioning and treatment with hydrocortisone or with Nembutal and morphine. On the other hand, an increased production was observed following stimulation of the pituitary-adrenal system by exogenous histamine or corticotrophin. From these experiments it is concluded that the corticoid production in vitro reflects the activity of the adrenal cortex in vivo and hence can be used for the study of the latter function.

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Neuropeptide S Stimulates the Hypothalamo-Pituitary-Adrenal Axis and Inhibits Food Intake

Endocrinology ◽

10.1210/en.2005-1280 ◽

2006 ◽

Vol 147 (7) ◽

pp. 3510-3518 ◽

Cited By ~ 126

Author(s):

Kirsty L. Smith ◽

Michael Patterson ◽

Waljit S. Dhillo ◽

Sejal R. Patel ◽

Nina M. Semjonous ◽

...

Keyword(s):

Food Intake ◽

Hpa Axis ◽

Paraventricular Nucleus ◽

Arginine Vasopressin ◽

Lateral Ventricle ◽

Neuropeptide S ◽

Plasma Acth ◽

Vasopressin Release ◽

Pituitary Adrenal Axis ◽

Stimulation Of

Neuropeptide S (NPS) is a recently discovered peptide shown to be involved in the modulation of arousal and fear responses. It has also been shown that lateral ventricle administration of NPS causes a significant decrease in food intake. Neuropeptides involved in the modulation of arousal have been shown to be involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis and food intake. In this study, we have examined the effect of intracerebroventricular (ICV) administration of NPS on behavior, regulation of the HPA axis, and food intake. ICV NPS significantly increased plasma ACTH and corticosterone 10 and 40 min after injection, respectively. A single ICV injection of NPS caused a significant increase in rearing activity as well as ambulatory movement for up to 45 min after injection. We then studied the effect of paraventricular nucleus (PVN) administration of NPS on the regulation of the HPA axis, behavior, and food intake. There was a significant increase in plasma ACTH and corticosterone after a single NPS PVN injection. Incubation of hypothalamic explants with increasing concentrations of NPS caused a significant increase in CRH and arginine vasopressin release. In addition, PVN administration of NPS dose-dependently inhibited food intake in the first hour after injection, although no effect on food intake was seen after this time. PVN administration of NPS caused a significant increase in rearing activity. These data demonstrate a novel role for NPS in the stimulation of the HPA axis.

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Serotonin depletion does not alter lipopolysaccharide-induced activation of the rat paraventricular nucleus

Journal of Endocrinology ◽

10.1677/joe.0.1560245 ◽

1998 ◽

Vol 156 (2) ◽

pp. 245-251 ◽

Cited By ~ 15

Author(s):

GL Conde ◽

D Renshaw ◽

SL Lightman ◽

MS Harbuz

Keyword(s):

Hpa Axis ◽

Paraventricular Nucleus ◽

Plasma Corticosterone ◽

Mrna Levels ◽

Dependent Manner ◽

Experimental Conditions ◽

Serotonin Depletion ◽

Corticotrophin Releasing Factor ◽

Subsequent Activation ◽

High Doses

We have investigated the effects of serotonin depletion on immune-mediated activation of the hypothalamo-pituitary-adrenal (HPA) axis. Corticotrophin-releasing factor (CRF) mRNA, c-fos mRNA and Fos peptide responses in the paraventricular nucleus (PVN) together with circulating levels of corticosterone were assessed in response to i.p. injections of three doses of lipopolysaccharide (LPS) both in control animals and animals pretreated with p-chlorophenylalanine (PCPA). Conscious animals received either an i.p. injection of 0.5 ml saline or 200 mg/kg PCPA in 0.5 ml saline on 2 consecutive days. This treatment resulted in a 93% depletion of serotonin on the fourth day. On day 4, animals received i.p. injections of LPS (2.5 mg/0.5 ml saline, 250 micrograms/0.5 ml or 50 micrograms/0.5 ml; E. coli 055:B5), or saline injections as controls. Pretreatment with PCPA had no effect on the basal levels of corticosterone, or on the elevated levels induced by the three doses, of LPS. Fos peptide and c-fos mRNA were undetectable in control animals, and Fos-like immunoreactivity increased in a dose-dependent manner following i.p. LPS in both control and PCPA-pretreated animals. C-fos mRNA expression induced by LPS was unaffected by serotonin depletion. Following the lowest dose of LPS, CRF mRNA did not change above control levels, however, the medium and high doses of LPS produced a significant (P < 0.05) increase in CRF mRNA levels in both depleted and intact animals. To confirm the temporal effects of serotonin depletion on activation of the HPA axis we collected plasma at 30 min, 1, 2, 3, 4, 5, and 6 h after LPS in both intact and serotonin-depleted animals. No significant differences in plasma corticosterone levels were found at any of the time points between intact and depleted animals. It appears that, at least under these experimental conditions, serotonergic inputs do not seem to play a major role in mediating the effects of LPS on changes in mRNA levels in the PVN or on the subsequent activation of the HPA axis.

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Endocrine and Electrolyte Balances during Periovulatory Period in Cycling Mares

Animals ◽

10.3390/ani11020520 ◽

2021 ◽

Vol 11 (2) ◽

pp. 520 ◽

Cited By ~ 1

Author(s):

Katiuska Satué ◽

Esterina Fazio ◽

Ana Muñoz ◽

Pietro Medica

Keyword(s):

Estrous Cycle ◽

Hpa Axis ◽

Adrenocorticotropic Hormone ◽

Venous Blood ◽

Competitive Elisa ◽

Direct Relation ◽

Plasma Acth ◽

Blood Samples ◽

Hypothalamic Pituitary Adrenal ◽

Stimulation Of

In cycling females, the periovulatory period is characterized by stimulation of the hypothalamic pituitary adrenal (HPA) axis. The aim of present study was to analyze the pattern and interrelationships among adrenocorticotropic hormone (ACTH), cortisol (CORT), aldosterone (ALD) and electrolytes (sodium—Na+, potassium—K+ and chloride—Cl−) during periovulatory period in cycling mares. Venous blood samples were obtained daily from a total of 23 Purebred Spanish broodmares, aged 7.09 ± 2.5 years, from day −5 to day +5 of estrous cycle, considering day 0, the day of ovulation. Plasma ACTH was measured by a fluorescent immunoassay kit, serum CORT and ALD by means of a competitive ELISA immunoassay, and plasma Na+, K+ and Cl− were quantified by an analyzer with selective electrodes for the three ions. ACTH showed higher concentrations at day 0 compared to days −5 to −1 and +1 to +3 (p < 0.05). CORT showed higher concentrations at day 0 compared to days −5 to −2 and +1 to +5 (p < 0.05). ALD showed higher concentrations at day 0 compared to days −5 to −2 (p < 0.05) and +2 (p < 0.05). Na+ and Cl− showed higher concentrations at day 0, compared to day −5 and +5. K+ showed lower concentrations at day 0 compared to day +1 (p < 0.05). The significant correlations obtained between ACTH and CORT (r = 0.20) and between ACTH and ALD (r = 0.32) suggest that although ACTH may have an effect both on CORT and ALD, there are other very important determinants that could be considered. Hence, it is possible to presume that the pituitary adrenocortical response and ALD may be involved in the ovulatory mechanisms without a direct relation with electrolyte pattern.

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Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways

Journal of the American Society of Nephrology ◽

10.1681/asn.2017121268 ◽

2018 ◽

Vol 29 (6) ◽

pp. 1720-1730 ◽

Cited By ~ 6

Author(s):

Miriam Zacchia ◽

Xuefei Tian ◽

Enrica Zona ◽

Robert J. Alpern ◽

Patricia A. Preisig

Keyword(s):

Proximal Tubule ◽

Signaling Pathways ◽

Cultured Cells ◽

Wild Type ◽

Experimental Conditions ◽

Opossum Kidney ◽

Citrate Transporter ◽

Stimulation Of

Background Urine citrate is reabsorbed exclusively along the renal proximal tubule via the apical Na+-dicarboxylate cotransporter NaDC-1. We previously showed that an acid load in vivo and media acidification in vitro increase NaDC-1 activity through endothelin-1 (ET-1)/endothelin B (ETB) signaling. Here, we further examined the signaling pathway mediating acid-induced NaDC-1 activity.Methods We transiently transfected cultured opossum kidney cells, a model of the proximal tubule, with NaDC-1 and ETB and measured [14C]-citrate uptake after media acidification under various experimental conditions, including inactivation of Pyk2 and c-Src, which were previously shown to be activated by media acidification. Wild-type (Pyk2+/+) and Pyk2-null (Pyk2−/−) mice were exposed to NH4Cl loading and euthanized after various end points, at which time we harvested the kidneys for immunoblotting and brush border membrane NaDC-1 activity studies.Results Inhibition of Pyk2 or c-Src prevented acid stimulation but not ET-1 stimulation of NaDC-1 in vitro. Consistent with these results, NH4Cl loading stimulated NaDC-1 activity in kidneys of wild-type but not Pyk2−/− mice. In cultured cells and in mice, ERK1/2 was rapidly phosphorylated by acid loading, even after Pyk2 knockdown, and it was required for acid but not ET-1/ETB stimulation of NaDC-1 in vitro. Media acidification also induced the phosphorylation of Raf1 and p90RSK, components of the ERK1/2 pathway, and inhibition of these proteins blocked acid stimulation of NaDC-1 activity.Conclusions Acid stimulation of NaDC-1 activity involves Pyk2/c-Src and Raf1-ERK1/2-p90RSK signaling pathways, but these pathways are not downstream of ET-1/ETB in this process.

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Production of corticosterone and testosterone in scorbutic mutant rats: difference of in vivo production between adrenal gland and testis

Acta Endocrinologica ◽

10.1530/acta.0.1240425 ◽

1991 ◽

Vol 124 (4) ◽

pp. 425-433 ◽

Cited By ~ 5

Author(s):

Haruki Fukuda ◽

Yasuhiro Ito ◽

Ryouji Hirota ◽

Motomu Tsuji ◽

Hiroshi Mori

Keyword(s):

Ascorbic Acid ◽

Adrenal Gland ◽

Steroid Hormones ◽

Mutant Strain ◽

Seminal Vesicles ◽

Plasma Acth ◽

Chronic Stimulation ◽

Testosterone Levels ◽

Stimulation Of

Abstract. Effects of deficiency in ascorbic acid on in vivo production of corticosterone and testosterone were examined using a mutant strain of rats unable to synthesize ascorbic acid. The adrenal weight of scorbutic rats was larger, and corticosterone levels in plasma and adrenal tissues were higher than those of ascorbic acid-supplied (ascorbutic) rats. Acute and chronic stimulation with ACTH increased corticosterone levels in both ascorbutic and scorbutic rats. In contrast, weights of seminal vesicles and ventral prostates in unstimulated scorbutic rats were smaller, and testosterone levels in plasma and testicular tissues were lower than those in ascorbutic rats. Acute stimulation with hCG increased testosterone levels only slightly in plasma and not in testicular tissues of scorbutic rats, when testosterone levels in ascorbutic rats reached a maximum. Chronic stimulation with hCG increased testosterone levels remarkably in both ascorbutic and scorbutic rats. These findings seem to indicate that ascorbic acid is not essential for the synthesis of steroid hormones. The scurvy seems to increase plasma ACTH levels secondary to the stress, resulting in the stimulation of the adrenals. In contrast, a prolonged deficiency in ascorbic acid appears to decrease plasma gonadotropin levels, and may reduce the sensitivity of testes to gonadotropins.

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Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis

Journal of Endocrinology ◽

10.1677/joe.0.1410497 ◽

1994 ◽

Vol 141 (3) ◽

pp. 497-503 ◽

Cited By ~ 23

Author(s):

P J Larsen ◽

J D Mikkelsen ◽

D Jessop ◽

S L Lightman ◽

H S Chowdrey

Keyword(s):

Hpa Axis ◽

Restraint Stress ◽

Acute Stress ◽

Monosodium Glutamate ◽

Plasma Corticosterone ◽

Mrna Levels ◽

Plasma Acth ◽

Corticotrophin Releasing Factor ◽

Acute And Chronic Stress ◽

Corticosterone Response

Abstract We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 ± 7 pg/ml) compared with controls (71 ± 18 pg/ml) while corticosterone levels were elevated (523 ± 84 ng/ml compared with 176 ± 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 ± 92 ng/ml compared with 628 ± 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 ± 24 pg/ml and 167 ± 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 ± 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma corticosterone, and restores the adrenocortical response to stress which is absent in chronically osmotically stimulated rats. The evidence is consistent with the suggestion that MSG lesions a pathway involved in tonic inhibition of the HPA axis. In addition, the adrenocortical sensitivity to ACTH and other secretagogues may be increased in MSG-treated animals. Journal of Endocrinology (1994) 141, 497–503

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Is thyrotropin-releasing hormone immunoreactivity in peripheral blood an estimate for hypothalamic thyrotropin-releasing hormone release?

Acta Endocrinologica ◽

10.1530/acta.0.1260276 ◽

1992 ◽

Vol 126 (3) ◽

pp. 276-281 ◽

Cited By ~ 1

Author(s):

Wim J de Greef ◽

Jan MM Rondeel ◽

Rogier Heide ◽

Wim Klootwijk ◽

Theo J Visser

Keyword(s):

Peripheral Blood ◽

Thyrotropin Releasing Hormone ◽

Portal Blood ◽

Hormone Release ◽

Experimental Conditions ◽

Releasing Hormone ◽

Two Peaks ◽

Hypophysial Portal ◽

Stimulation Of

The significance of TRH for pituitary function is still unresolved mainly due to limitations in determining in vivo hypothalamic TRH release. We therefore examined whether TRH immunoreactivity (TRH-IR) in peripheral blood is an index for hypothalamic TRH release. Peripheral TRH-IR varied between 10 and 55 pmol/l and was similar in euthyroid and hypothyroid rats, but lower in hyperthyroid rats. Destruction of the hypothalamic paraventricular area reduced peripheral TRH-IR, while stimulation of this area increased it. Clearance of TRH during continuous TRH infusion was 1.9±0.2, 3.5±0.3 and 5.9±0.8 ml/min in hypothyroid, euthyroid and hyperthyroid rats, respectively. These and previous data on TRH in hypophysial portal blood indicate that 5–25 pmol TRH/I peripheral blood is of hypothalamic origin. Chromatography revealed that TRH-IR from hypothalamus and portal blood co-eluted with TRH, but in peripheral blood two peaks were found, one of which was authentic TRH. Thus, peripheral TRH-IR alters in experimental conditions and part of it seems to be of hypothalamic origin. However, the presence of TRH-like material in peripheral blood not identical to TRH and the fact that experimental conditions alter TRH clearance indicate that peripheral TRH-IR is not an index for hypothalamic TRH release.

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Network dynamics of hypothalamic feeding neurons

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2011140118 ◽

2021 ◽

Vol 118 (14) ◽

pp. e2011140118

Author(s):

Patrick Sweeney ◽

Can Chen ◽

Indika Rajapakse ◽

Roger D. Cone

Keyword(s):

Paraventricular Nucleus ◽

Energy State ◽

Critical Role ◽

Network Dynamics ◽

Network Activity ◽

Energy Deficit ◽

Valuable Insight ◽

Stimulation Of

Mutations in the melanocortin 4 receptor (MC4R) result in hyperphagia and obesity and are the most common cause of monogenic obesity in humans. Preclinical rodent studies have determined that the critical role of the MC4R in controlling feeding can be mapped in part to its expression in the paraventricular nucleus of the hypothalamus (paraventricular nucleus [PVN]), where it regulates the activity of anorexic neural circuits. Despite the critical role of PVN MC4R neurons in regulating feeding, the in vivo neuronal activity of these cells remains largely unstudied, and the network activity of PVN MC4R neurons has not been determined. Here, we utilize in vivo single-cell endomicroscopic and mathematical approaches to determine the activity and network dynamics of PVN MC4R neurons in response to changes in energy state and pharmacological manipulation of central melanocortin receptors. We determine that PVN MC4R neurons exhibit both quantitative and qualitative changes in response to fasting and refeeding. Pharmacological stimulation of MC4R with the therapeutic MC4R agonist setmelanotide rapidly increases basal PVN MC4R activity, while stimulation of melanocortin 3 receptor (MC3R) inhibits PVN MC4R activity. Finally, we find that distinct PVN MC4R neuronal ensembles encode energy deficit and energy surfeit and that energy surfeit is associated with enhanced network connections within PVN MC4R neurons. These findings provide valuable insight into the neural dynamics underlying hunger and energy surfeit.

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Genetic control of specific immune suppression. I. Experimental conditions for the stimulation of suppressor cells by the copolymer L-glutamic acid50-L-tyrosine50 (GT) in nonresponder BALB/c mice.

Journal of Experimental Medicine ◽

10.1084/jem.142.6.1436 ◽

1975 ◽

Vol 142 (6) ◽

pp. 1436-1446 ◽

Cited By ~ 56

Author(s):

P Debré ◽

J A Kapp ◽

B Benacerraf

Keyword(s):

Immune Suppression ◽

Suppressor Cells ◽

Random Copolymer ◽

Inbred Strains ◽

Experimental Conditions ◽

Inbred Strains Of Mice ◽

Specific Igg ◽

Synthetic Polypeptide ◽

Stimulation Of

In the present studies we have confirmed that the random copolymer of L-glutamic acid50-L-tyrosine50 (GT) fails to induce an antibody response in a large number of inbred strains of mice. Nevertheless, GT complexed to methylated bovine serum albumin (MBSA) elicits a GT-specific IgG PFC response in vivo. Furthermore, injection of BALB/c mice with 10 to 100 mug of GT specifically decreases their ability to develop anti-GT PFC responses to a subsequent challenge with GT-MBSA. GT-specific tolerance can be transferred to normal, syngeneic recipients by spleen cells or thymocytes of GT-primed animals. These results indicate that the stimulation of suppressor cells can be observed in nonresponder mice with another synthetic polypeptide besides GAT. Various parameters of GT-specific immunosuppression in BALB/c mice are described. The application of these techniques to the study of the genetic factors controlling the stimulation of specific immune suppression is discussed.

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