α-MSH Levels Research Articles

Plasma α–melanocyte-stimulating hormone: sex differences and correlations with obesity

Rodent experiments raise the possibility of a regulatory role of peripheral α–melanocyte-stimulating hormone ( α-MSH) in obesity and metabolism, but human data on peripheral α-MSH levels remain fragmentary. Because of the possible relationship between α-MSH and obesity, we endeavored to test the hypothesis that higher levels of α-MSH in obese patients would correlate with leptin levels and with other markers of obesity. Sixty normal-weight to obese healthy men and women participated. Weight, measures of body composition, and diet diaries were obtained; fasting blood was analyzed for α-MSH, lipids, glucose, insulin, leptin, and adiponectin. To begin to understand the source of peripherally measured hormones, α-MSH was also measured in serum samples from 5 individuals with untreated Addison disease. Levels of α-MSH were higher in men vs women (10.1 ± 4.3 vs 7.6 ± 3.4 pmol/L, P = .019), and α-MSH levels were higher in patients with Addison disease vs controls (17.7 ± 2.3 vs 8.7 ± 0.52 pmol/L, P < .001). Measures of adiposity correlated with insulin and leptin in men and women, and with adiponectin in women. α–Melanocyte-stimulating hormone levels did not correlate significantly with any parameter of adiposity or diet composition. The elevated α-MSH levels in patients with untreated Addison disease suggest possible pituitary secretion of α-MSH to the periphery. The lack of correlation between peripheral α-MSH and parameters of adiposity suggests that endogenous plasma α-MSH levels are not a metric for body composition per se.

Profiles of α-melanocyte-stimulating hormone in the Japanese flounder as revealed by a newly developed time-resolved fluoroimmunoassay and immunohistochemistry

Profiles of α-melanocyte-stimulating hormone (α-MSH) in the Japanese flounder were examined by a newly developed time-resolved fluoroimmunoassay (TR-FIA) and immunohistochemistry. A TR-FIA for α-MSH was newly developed, and its levels in the pituitary gland and plasma of Japanese flounder reared in a white or black tank for 5 months were compared. A competitive assay using two antibodies was performed among secondary antibodies in the solid phase, α-MSH antibodies, samples, and europium-labeled Des-Ac-α-MSH. The sensitivity of the assay, defined as twice the standard deviation at a zero dose, was 0.98 ng/ml (49 pg/well). The intra- and interassay coefficients of variation of the assay were 8.8% ( n = 8) and 17.3% ( n = 5), respectively, at about 50% binding. Cross-reactivities of Des-Ac-α-MSH and Di-Ac-α-MSH were about 100%. Cross-reactivities of adrenocorticotropic hormone, salmon gonadotropin-releasing hormone (sGnRH), and chicken GnRH-II were less than 0.2%, and that of melanin-concentrating hormone was less than 2.0% at 50% binding. Displacement curves of serially twofold-diluted hypothalamus extract, pituitary gland extract, and plasma extract of Japanese flounder with the assay buffer were parallel to the α-MSH standard curve. Moreover, displacement curves of serially twofold-diluted hypothalamus and/or pituitary gland extract of masu salmon, goldfish, red seabream, Japanese eel, tiger puffer, and barfin flounder with the assay buffer were also parallel to the α-MSH standard. In Japanese flounder, total immunoreactive (ir)-α-MSH levels in the pituitary gland were lower in the black tank, whereas those in the plasma tended to be higher in the black tank, suggesting that the synthesis and release of α-MSH are higher in the black tank. α-MSH-ir cells were detected in the pars intermedia and a small part of the pars distalis of the pituitary gland. α-MSH-ir cell bodies were located in the basal hypothalamus and α-MSH-ir fibers were distributed not only in the hypothalamus but also in the telencephalon, midbrain, cerebellum, and medulla oblongata, suggesting that α-MSH functions as a neuromodulator in the brain.

Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.)

The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

Central and peripheral interleukin-1β and interleukin-1 receptor I expression and their role in the acute stress response of common carp, Cyprinus carpio L.

In fish, the hypothalamus-pituitary-interrenal axis (HPI-axis), the equivalent of the hypothalamus-pituitary-adrenal axis (HPA-axis) in mammals, is activated during stress and leads to production and release of cortisol by the interregnal cells in the head kidney. In mammals, the cytokine interleukin-1beta (IL-1beta) takes a key position in the innate immune and inflammatory responses and influences the HPA-axis. In fish, studies that address the effects of cytokines on HPI-axis activation are limited. We quantitatively assessed expression of IL-1beta and its receptor, IL-1RI (the latter was cloned and sequenced), in an acute restraint stress paradigm in common carp, Cyprinus carpio. We also considered expression of the pituitary hormones prolactin (PRL) and GH that have been shown to be structurally related to cytokines and have immunomodulatory actions. Pituitary PRL expression increased fourfold during stress; GH mRNA levels were unaffected. Following restraint, hypothalamic IL-1beta expression was upregulated; in head kidney and pituitary pars intermedia, IL-1RI expression significantly increased. We suggest that during acute stress IL-1beta signalling in the HPI-axis becomes more sensitive, since both ligand and receptor expressions are enhanced. In vitro, recombinant carp IL-1beta stimulates release of alpha-MSH and N-Ac beta-endorphin from the pituitary gland. This observation concurs with increased in vivo plasma levels of alpha-MSH and N-Ac beta-endorphin following restraint. Our findings combined lead us to conclude that IL-1beta affects the activity of the HPI-axis and, in turn, expression profiles of genes encoding IL-1beta and its receptor are modified during acute stress. Our study provides convincing evidence for bi-directional communication of the HPI-axis and the immune system in fish.

Central Neurotranspeptide, Alpha-Melanocyte-Stimulating Hormone (.ALPHA.-MSH) is Upregulated in Patients with Congestive Heart Failure

Alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin (POMC) derivative, is a neuropeptide with potent anti-inflammatory properties that inhibits tissue injury in a wide array of inflammation models. To determine if alpha-MSH is involved in the development of congestive heart failure (CHF) with the specific aim of examining its peripheral source and one of the mechanisms. The circulating levels of alpha-MSH were measured in 115 patients with CHF using a double-antibody radioimmunoassay. To determine one of the sources of circulating alpha-MSH, human peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha. Furthermore, to clarify one of the functions of alpha-MSH, PBMC were cultured in the presence or absence of alpha-MSH. Plasma levels of alpha-MSH were significantly higher in NYHA class II patients with CHF than in control subjects (p<0.0001). A significant correlation was found between the levels of alpha-MSH and high-sensitive testing for C-reactive protein in patients with CHF (r=0.41, p<0.0005). PBMC stimulated with LPS or TNF-alpha released alpha-MSH in a concentration-dependent manner. alpha-MSH inhibited LPS-induced TNF-alpha production, and alpha-MSH simultaneously augmented production of interleukin (IL)-10 by PBMC. Circulating alpha-MSH was increased in patients with CHF. Inflammatory response induced alpha-MSH production in cultured human PBMC. Treatment of alpha-MSH could modify the immunobalance between inflammatory and anti-inflammatory responses in cultured PBMC. These findings suggest that alpha-MSH may play an important role in the pathophysiology of CHF.

AgRP (83–132) and SHU9119 differently affect activity-based anorexia

Activity-based anorexia (ABA) mimics starvation and hyperactivity of anorexia nervosa patients in rats. Activation of the melanocortin (MC) system leads to hypophagia and increased energy expenditure in ad libitum fed rats. Therefore, activation of the MC system might underlie the development and propagation of ABA. Pro-opiomelanocortin (POMC) gene expression is normally decreased during negative energy balance. Strikingly, we found a transient up-regulation of POMC mRNA levels in the arcuate nucleus during the development of ABA, indicating a hyperactive MC system. However, wheel running and food intake were not influenced by treating ABA rats with the competitive antagonist SHU9119. This suggests that agonism of MC receptors by endogenous α-melanocyte-stimulating hormone (α-MSH) levels does not underlie ABA. Instead, treatment with the inverse agonist AgRP (83–132) did ameliorate signs of ABA. This implies that modulation of constitutive MC receptor activity rather than antagonizing putative α-MSH release contributes to the development and propagation of ABA.

The acute stress response of red porgy, Pagrus pagrus, kept on a red or white background

The skin colour of red porgy, Pagrus pagrus, can be modified by exposure to different background colours. Red and white background colours brighten the dark skin colour that develops under common culture conditions in red porgy. To assess whether skin colour is also modified by aquaculture related handling stress, we subjected red porgy to 5 min of netting stress combined with air exposure. Fish kept on a white background have: (1) a lighter skin colour, which is not influenced by an acute stressor, (2) a less saturated red colour, which significantly decreases 24 h post-handling, and (3) a similar hue as fish kept on a red background. The first plasma parameters to rise after application of the stressor are cortisol, lactate and Na +; then, glucose levels rose. Other plasma ions (Ca 2+, Cl −, K +) were not affected up to 2 h post-stressor, but had decreased at 8 and 24 h after handling. Plasma pH decreased over the first 2 h post-handling, indicative of plasma acidosis upon air exposure. The acidosis then coincided with increases in plasma lactate levels. As αMSH levels were not significantly affected by the stressor while cortisol levels showed a five to tenfold increase, we suggest that following acute stress in red porgy, plasma cortisol release is controlled by ACTH, perhaps in combination with a sympathic stimulation.

Autoantibodies against neuropeptides are associated with psychological traits in eating disorders

Previously, we identified that a majority of patients with anorexia nervosa (AN) and bulimia nervosa (BN) as well as some control subjects display autoantibodies (autoAbs) reacting with alpha-melanocyte-stimulating hormone (alpha-MSH) or adrenocorticotropic hormone, melanocortin peptides involved in appetite control and the stress response. In this work, we studied the relevance of such autoAbs to AN and BN. In addition to previously identified neuropeptide autoAbs, the current study revealed the presence of autoAbs reacting with oxytocin (OT) or vasopressin (VP) in both patients and controls. Analysis of serum levels of identified autoAbs showed an increase of IgM autoAbs against alpha-MSH, OT, and VP as well as of IgG autoAbs against VP in AN patients when compared with BN patients and controls. Further, we investigated whether levels of these autoAbs correlated with psychological traits characteristic for eating disorders. We found significantly altered correlations between alpha-MSH autoAb levels and the total Eating Disorder Inventory-2 score, as well as most of its subscale dimensions in AN and BN patients vs. controls. Remarkably, these correlations were opposite in AN vs. BN patients. In contrast, levels of autoAbs reacting with adrenocorticotropic hormone, OT, or VP had only few altered correlations with the Eating Disorder Inventory-2 subscale dimensions in AN and BN patients. Thus, our data reveal that core psychobehavioral abnormalities characteristic for eating disorders correlate with the levels of autoAbs against alpha-MSH, suggesting that AN and BN may be associated with autoAb-mediated dysfunctions of primarily the melanocortin system.

Background adaptation and water acidification affect pigmentation and stress physiology of tilapia, Oreochromis mossambicus

The ability to adjust skin darkness to the background is a common phenomenon in fish. The hormone α-melanophore-stimulating hormone (αMSH) enhances skin darkening. In Mozambique tilapia, Oreochromis mossambicus L., αMSH acts as a corticotropic hormone during adaptation to water with a low pH, in addition to its role in skin colouration. In the current study, we investigated the responses of this fish to these two environmental challenges when it is exposed to both simultaneously. The skin darkening of tilapia on a black background and the lightening on grey and white backgrounds are compromised in water with a low pH, indicating that the two vastly different processes both rely on αMSH-regulatory mechanisms. If the water is acidified after 25 days of undisturbed background adaptation, fish showed a transient pigmentation change but recovered after two days and continued the adaptation of their skin darkness to match the background. Black backgrounds are experienced by tilapia as more stressful than grey or white backgrounds both in neutral and in low pH water. A decrease of water pH from 7.8 to 4.5 applied over a two-day period was not experienced as stressful when combined with background adaptation, based on unchanged plasma pH and plasma αMSH, and Na levels. However, when water pH was lowered after 25 days of undisturbed background adaptation, particularly αMSH levels increased chronically. In these fish, plasma pH and Na levels had decreased, indicating a reduced capacity to maintain ion-homeostasis, implicating that the fish indeed experience stress. We conclude that simultaneous exposure to these two types of stressor has a lower impact on the physiology of tilapia than subsequent exposure to the stressors.

ACTH, α-MSH, and control of cortisol release: cloning, sequencing, and functional expression of the melanocortin-2 and melanocortin-5 receptor in Cyprinus carpio

Cortisol release from fish head kidney during the acute phase of the stress response is controlled by the adrenocorticotropic hormone (ACTH) from the pituitary pars distalis (PD). Alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin, from the pars intermedia (PI), have been implicated in cortisol release during the chronic phase. The present study addresses the regulation of cortisol release by ACTH and alpha-MSH in common carp (Cyprinus carpio) and includes characterization of their receptors, namely, the melanocortin-2 and melanocortin-5 receptors (MC2R and MC5R). We could not demonstrate corticotropic activity of alpha-MSH, beta-endorphin, and combinations of these. We do show a corticotrope in the PI, but its identity is as yet uncertain. Carp restrained for 1 and 7 days showed elevated plasma cortisol and alpha-MSH levels; cortisol is still elevated but lower at day 7 than day 1 of restraint. Interrenal response capacity is unaffected, as estimated by stimulation with a maximum dose ACTH in a superfusion setup. MC2R and MC5R appear phylogenetically well conserved. MC2R is predominantly expressed in head kidney; a low abundance was found in spleen and kidney. MC5R is expressed in brain, pituitary PD, kidney, and skin. Quantitative PCR analysis of MC2R and MC5R expression in the head kidney of restrained fish reveals MC2R mRNA downregulation after 7 days restraint, in line with lower plasma cortisol levels seen. We discuss regulation of corticosteroid production from a phylogenetic perspective. We propose that increased levels of alpha-MSH exert a positive feedback on hypothalamic corticotropin-releasing hormone release to sustain a mild stress axis activity.

Plasma α-MSH and acetylated β-endorphin levels following stress vary according to CRH sensitivity of the pituitary melanotropes in common carp, Cyprinus carpio

Pituitary melanotropes release α-melanocyte-stimulating hormone (α-MSH) and acetylated β-endorphin (NAc β-end) during stress responses. However, effects of stressors on plasma concentrations of these hormones are highly inconsistent among fish species. Here, we show that also within a species, the common carp ( Cyprinus carpio), fish sometimes respond with elevated α-MSH and NAc β-end plasma levels, and at other times not. The origin of this variable response was investigated by (1) studying the effects of corticotropin-releasing hormone (CRH) on α-MSH and NAc β-end release in vitro, (2) establishing where in the second messenger pathway coupled to CRH receptors melanotrope responsiveness is determined, and (3) testing modulatory actions of other hypothalamic factors (here opioid β-endorphin). Melanotropes were in a high or low responsive state to CRH in vitro, which was especially evident when tissue was tested from fish kept at higher ambient water temperatures, and this correlates with the variability in α-MSH and NAc β-end responses in vivo. Relative rates of α-MSH and NAc β-end release following stimulation with CRH in vitro match plasma level changes in vivo, and this indicates that the CRH pathway does act in vivo. cAMP did not stimulate melanotropes in the low responsive state to release hormones in vitro. Thus, the mechanism that determines the cell status, occurs downstream of cAMP accumulation. Opioid β-endorphin differentially modulated the actions of CRH, as NAc β-end, but not α-MSH, release was inhibited. This response was not observed in the stress paradigms studied. We conclude that the variation in α-MSH and NAc β-end stress responses in vivo correlates with many CRH responses in vitro; whether a cell is in a high or low responsive state to CRH is determined downstream of accumulation of the second messenger. We propose that melanotropes have to be in the high responsive state to be activated by CRH during stress in carp and other teleosts.

N-acetylation of hypothalamic alpha-melanocyte-stimulating hormone and regulation by leptin.

The central melanocortin system is critical in the regulation of appetite and body weight, and leptin exerts its anorexigenic actions partly by increasing hypothalamic proopiomelanocortin (POMC) expression. The POMC-derived peptide alpha-melanocyte-stimulating hormone (alphaMSH) is a melanocortin 4 receptor agonist, and its potency in reducing energy intake is strongly increased by N-acetylation. The reason for the higher biological activity of N-acetylated alphaMSH (Act-alphaMSH) compared with that of N-desacetylated alphaMSH (Des-alphaMSH) is unclear, and regulation of acetylation by leptin has not been investigated. We show here that total hypothalamic alphaMSH levels are decreased in leptin-deficient ob/ob mice and increased in leptin-treated ob/ob and C57BL/6J mice. The increase in total alphaMSH occurred as soon as 3 h after leptin injection and was entirely due to an increase in Act-alphaMSH. Consistent with this observation, leptin rapidly induced the enzymatic activity of a N-acetyltransferase in the hypothalamus of mice. In 293T cells expressing the melanocortin 4 receptor, Act-alphaMSH is far more potent than Des-alphaMSH in stimulating cAMP accumulation, an effect caused by a dramatically increased stability of Act-alphaMSH. Moreover, Des-alphaMSH is rapidly degraded in the hypothalamus after intracerebroventricular injection in rats and was less potent in inhibiting energy intake. The results suggest that leptin activates a N-acetyltransferase in POMC neurons, leading to increased hypothalamic levels of Act-alphaMSH. Due to its increased stability, this posttranslational modification of alphaMSH may play a critical role in leptin action via the central melanocortin pathway.

Background colour influence on the stress response in cultured red porgy Pagrus pagrus

Red porgy Pagrus pagrus were placed and maintained in white, grey and black background fibreglass tanks for 2 weeks. Additionally, fish kept in white and black background tanks were then subjected to crowding stress. After 2, 9, 16 and 23 days, blood samples were taken and plasma cortisol, alpha melanocyte stimulating hormone (α-MSH) and glucose values were analysed and compared with values from uncrowded fish from white or black tanks. Measurements of plasma cortisol and α-MSH in unstressed red porgy from white, grey and black tanks revealed no significant differences among the three groups. However, the results show that background colour markedly affects the in vitro interrenal sensitivity to both α-MSH and ACTH, as interrenal cells from black adapted fish had become virtually unresponsive to both secretagogues. Crowded fish on a black background showed a prominent increase in plasma cortisol after 2 days, which was followed by a recovery. In fish crowded on a white background however, the increase of cortisol was lower but was maintained through the entire experiment. Plasma α-MSH levels increased at 23 days as a consequence of crowding; this increase was also dependent on the background, being more prominent in fish placed in white background tanks. Thus, in the red porgy, a white background appears to modify the stress response, particularly in the long term.

Proopiomelanocortin-Derived Peptides in Rat Cerebrospinal Fluid and Hypothalamic Extracts: Evidence that Secretion Is Regulated with Respect to Energy Balance

Regulation of proopiomelanocortin (POMC) is an important means of controlling the central melanocortin system. It has never been established whether the spectrum of POMC-derived peptides synthesized and secreted from the hypothalamus is altered in response to changes in energy homeostasis in vivo. To monitor secretion, we analyzed peptide content of rat cerebrospinal fluid. Strikingly, both the POMC precursor and ACTH were readily detected. Moreover, levels of both were lower in samples from obese Zucker rats (fa/fa) vs. lean Zucker rats (+/+, fa/+) and from fasted vs. fed rats, whereas alpha MSH could not be detected. POMC levels were also decreased in hypothalamic extracts from obese and fasted animals. In contrast, despite being the most predominant peptide in extracts, alpha MSH levels were not significantly changed in any of the rat models. The ratio of precursor to derived peptides in cerebrospinal fluid was significantly higher in obese vs. lean and fed vs. fasted rats, indicating that secretion of POMC-derived peptides is differentially down-regulated during negative energy balance. In contrast to peptide analysis, we found that POMC gene expression was not significantly decreased in fasted rat hypothalami. We conclude that regulation of peptide secretion is an important mechanism by which the POMC system is controlled.

Regulation of cellular α-MSH and β-endorphin during stimulated secretion from intermediate pituitary cells: involvement of aspartyl and cysteine proteases in the control of cellular levels of α-MSH and β-endorphin

The regulation of cellular levels of α-melanocyte stimulating factor (α-MSH) and β-endorphin in response to stimulated secretion from intermediate pituitary cells in primary culture was investigated in this study. Regulation of the cell content of α-MSH and β-endorphin occurred in two phases consisting of (a) initial depletion of cellular levels of these peptide hormones during short-term secretion (3 h) induced by isoproterenol, forskolin, or phorbol myristate acetate (PMA) which was followed by (b) long-term (24 h) increases in cellular levels of α-MSH and β-endorphin in response to stimulated secretion induced by isoproterenol and PMA. In short-term experiments (3 h), cellular levels of α-MSH and β-endorphin were reduced by 30–50% during stimulated secretion of these peptide hormones by isoproterenol (agonist for the β-adrenergic receptor), forskolin that activates protein kinase A (PKA), and PMA that activates protein kinase C (PKC). Moreover, dopamine inhibited isoproterenol-induced depletion of cellular α-MSH and β-endorphin. During long-term incubation of cells (24 h) with isoproterenol, cellular α-MSH and β-endorphin were increased to twice that of controls (unstimulated cells). Treatment with PMA for 24 h also increased cellular levels of α-MSH and β-endorphin. Moreover, cellular levels of α-MSH and β-endorphin were decreased during long-term treatment of cells with an aspartyl protease inhibitor, pepstatin A, and with the cysteine protease inhibitor E64c. These results implicate aspartyl and cysteine proteases in the cellular production of α-MSH and β-endorphin that requires proteolytic processing of their common precursor proopiomelanocortin (POMC). These findings demonstrate the parallel regulation of cellular levels of α-MSH and β-endorphin during their cosecretion, which may involve aspartyl and cysteine proteases in the metabolism of these peptide hormones.

Diplodus sargus interrenal–pituitary response: chemical communication in stressed fish

In the present study the response of white sea-bream ( Diplodus sargus), used as experimental model, to different stocking densities was tested to assess whether the induced stress conditions were able to activate a chemical communication. Once a good recovery was evident, six days after capture and transportation, experiments started to evaluate eventual changes in cortisol plasma levels as well as in both plasma and pituitary α-melanocyte stimulating hormone (α-MSH) levels. These studies demonstrated that a low stocking density (2.5 kg/1000 L) is not deleterious for this species while a higher one (10 kg/1000 L) induces the activation of the hypothalamus–pituitary–interrenal axis (HPI). Thus, in these fish were evident both a significant increase of cortisol plasma levels and a significant decrease of α-MSH pituitary levels, while no significant changes were detected in α-MSH plasma concentrations. The most relevant result reported in this study, for the first time in marine species, is the presence of a chemical communication among stressed fish. It also should be noted that the data obtained from cortisol and α-MSH detections strongly indicate a gender specificity of this chemical signal.

Asphyxia-induced release of α-melanocyte-stimulating hormone in newborn pigs

Asphyxia and reperfusion induced changes in the plasma and cerebrospinal fluid (CSF) concentrations of α-melanocyte-stimulating hormone (α-MSH) were studied in newborn pigs using a specific radioimmunoassay technique. Cardiovascular and metabolic failure induced by neonatal asphyxia resulted in a 3-fold, significant ( P < 0.05) increase in plasma α-MSH levels, whereas the hormone concentration in CSF was significantly ( P < 0.05) reduced by 50% during postasphyxial reperfusion. Our data indicate an asphyxia-induced release of α-MSH, and suggest a discordant regulation of plasma and CSF concentrations in newborn pigs.

Pituitary and Interrenal Function in Gilthead Sea Bream (Sparus aurata L., Teleostei) after Handling and Confinement Stress

Dynamics of adrenocorticotropin (ACTH), α melanocyte-stimulating hormone (α-MSH), N-acetylated-β-endorphin (N-ac-β-END), cortisol, and growth hormone (GH) were investigated in gilthead sea bream (Sparus aurata) stressed by handling plus confinement. As indices of the secondary stress response, plasma levels of glucose, lactate, and plasma ions were monitored. Within 1 h, plasma cortisol and ACTH levels increased above the control values but GH levels decreased. Subsequently, at 24 h cortisol and ACTH levels had declined, but were still higher than in controls, whereas GH levels had recovered after 4 h. Regarding the melanotrope peptides, there were no differences in plasma levels of α-MSH and N-ac-β-END, but pituitary stores of these peptides were severely depleted already after 1 h, as were ACTH stores. Pituitary contents of proopiomelanocortin (POMC)-derived hormones did not show significant differences from 72 h onward. Therefore, the results indicate that both handling and confinement affected the corticotropes of the pars distalis and the melanotropes of the neurointermediate lobe but at different magnitudes. The possible involvement of corticotropin-releasing hormone (CRH) in the regulation of pituitary POMC-producing cell types under these conditions was indicated by the in vitro dose-dependent effect of the peptide on release of ACTH, α-MSH, and N-ac-β-END. The corticocotropes appeared more responsive, and approximately 10-fold more sensitive, to CRH compared with the melanotropes. The ACTH-releasing potency of 1 nM CRH was inhibited 75% following pretreatment of the whole pituitary gland with 400 nM of the CRH antagonist α-helical CRH9–41.

Inhibition of HPI axis response to stress in gilthead sea bream (Sparus aurata) with physiological plasma levels of cortisol

This study investigates the effect of corticosteroid (cortisol) administration on the stress response of the gilthead sea bream Sparus aurata subjected to a 48 h confinement. The effect of (in-vitro and in-vivo ) cortisol administration on the in-vitro ACTH sensitivity of the interrenal tissue; the plasma levels and tissue concentration of cortisol; and the plasma levels of ACTH, α-MSH, β-endorphin and glucose were determined. Confinement caused a transient and concomitant increase in plasma cortisol and ACTH levels. However, in cortisol-fed fish the plasma ACTH levels were lower, indicating a suppresion of the ACTH release from the corticotropes by cortisol. In contrast to the activation of the corticotropes, the levels of plasma melanotrope derived peptides were not affected. In spite of the fact that interrenal cells of cortisol-fed gilthead sea bream released less cortisol than controls, the interrenal sensitivity to ACTH was not affected by in-vivo and in-vitro cortisol administration. This suggests that the interrenal sensitivity to ACTH in stressed (confinement) sea bream is probably not regulated by α-MSH, N-ac-β-END, or by cortisol. Thus, in gilthead sea bream the interrenal sensitivity to ACTH could be regulated at the hypothalamus and/or pituitary and communicated via circulating ACTH levels.

A drop in ambient temperature results in a transient reduction of interrenal ACTH responsiveness in the gilthead sea bream (Sparus aurata, L.)

This study investigated the effects of a drop in water temperature (18 °C to 9 °C in 24 h) on the pituitary and interrenal hormones of the gilthead sea bream Sparus aurata. The in vitro sensitivity of the interrenal tissue to ACTH, plasma levels of cortisol, ACTH, α-MSH, GH, glucose, lactate and ions were determined. In vitro ACTH, stimulated the release of cortisol from isolated interrenal glands from control gilthead sea bream in a concentration dependent fashion. However, the interrenal cells were less sensitive to ACTH as soon as 24 h following the onset of the temperature drop. At this time, plasma cortisol and ACTH levels were raised, and plasma GH concentrations were decreased, whereas no significant changes were found in plasma α-MSH. After 96 h plasma ACTH levels had recovered whereas plasma cortisol levels were still higher than controls after 8 days of the beginning of the experiment. Interrenal sensitivity had recovered after 8 days. The results may help to clarify the relationship between the stress response and the aetiology of the winter syndrome in sea bream.