HIGH-INTENSITY EXERCISE TRAINING INDUCES MORPHOLOGICAL AND BIOCHEMICAL CHANGES IN SKELETAL MUSCLES

In the present study we investigated the effect of two different exercise protocols on fibre composition and metabolism of two specific muscles of mice: the quadriceps and the gastrocnemius. Mice were run daily on a motorized treadmill, at a velocity corresponding to 60% or 90% of the maximal running velocity. Blood lactate and body weight were measured during exercise training. We found that at the end of training the body weight significantly increased in high-intensity exercise mice compared to the control group (P=0.0268), whereas it decreased in low-intensity exercise mice compared to controls (P=0.30). In contrast, the food intake was greater in both trained mice compared to controls (P < 0.0001 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively). These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls (P=0.03 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively); in particular, blood lactate levels after high-intensity exercise were significantly lower than those measured in low-intensity exercise mice (P=0.0044). Immunoblotting analysis demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial enzymes contained within gastrocnemius and quadriceps muscles. These changes were associated with an increase in the amount of slow fibres in both these muscles of high-intensity exercise mice, as revealed by the counts of slow fibres stained with specific antibodies (P < 0.0001 for the gastrocnemius; P=0.0002 for the quadriceps). Our results demonstrate that high-intensity exercise, in addition to metabolic changes consisting of a decrease in blood lactate and body weight, induces an increase in the mitochondrial enzymes and slow fibres in different skeletal muscles of mice, which indicates an exercise-induced increase in the aerobic metabolism.     

Endurance exercise training causes adrenal medullary hypertrophy in young and old Fischer 344 rats.

The purpose of the present investigation was to determine the effects of endurance exercise training on adrenal medullary volume and epinephrine content in young (5 month) and old (23 month) female Fischer 344 rats. Animals from each group underwent 10 weeks of treadmill running (60 minutes per day, 5 days per week). 72 hours following the last training session animals were killed and the adrenal glands removed for subsequent analysis. Plantaris muscle citrate synthase activity increased with training in both young and old animals (39.8% young; 36.4% old). Trained animals had larger adrenal medullary volumes (48% increase in young, and 18% in old) than untrained controls. Trained animals also had higher total adrenal medullary epinephrine content (36% increase in young, and 24% in old). There were no differences in adrenal medullary epinephrine or norepinephrine concentration (micrograms/microliters medulla). It was concluded that the training-induced increase in adrenal epinephrine content is due to an increase in the size of the medulla, and not to a greater medullary epinephrine concentration. Furthermore, similar responses to training occur in both old and young animals.     

Morphometric and histological studies on the adrenal glands of the camel Camelus dromedarius

The adrenal gland of the camel consists of an outer cortex and an inner medulla. The general disposition of the cortex and medulla, however, differs occasionally from that of other mammals. Extensions of medulla could reach as far as the periphery of the cortex. Islet of medullary tissue may be found in sections of the cortex and cortical tissue consisting of all zones of the cortex may occur around arteries or nerves in the medulla. The medulla may be separated from the cortex by connective tissue especially in old camels. The arrangement of noradrenaline-secreting cells is different from that in other ruminants; they are found in groups scattered between the adrenaline-secreting cells. Bundles of smooth muscle occur in venules at the corticomedullary interface. Accessory adrenal glands are found embedded in the renal fat. They are similar in structure to the adrenal gland. The adrenal cortex forms 74% of the volume of the gland and the ratio of the cortex to medulla is 4:1. The zona glomerulosa, fasciculata and reticularis constitute about 13%, 53%, and 29% by volume of the cortex, respectively.     

Adrenal medulla and exercise training

The adrenaline release from the adrenal medulla increases during exercise, but at a given absolute work intensity the magnitude of this response is less pronounced in endurance trained vs sedentary individuals most likely due to a lower sympathetic stimulation of the adrenal medulla. However, when trained and untrained subjects are compared at identical relative work loads as well as in response to numerous non-exercise stimuli, endurance trained athletes have a higher epinephrine secretion capacity compared to sedentary individuals. This indicates a development of a so-called “sports adrenal medulla” as a result of a long term adaption of an endocrine gland to physical training. Such an adaptation is parallel to adaptations taking place in other tissues like skeletal muscle and the heart, and can be advantageous in relation to both exercise performance in the competing athlete and cause a biological rejuvenation in relation to aging. Accepted: 4 September 1997     

Effect of Oxotremorine on Ornithine Decarboxylase Activity of the Adrenal Gland in Rat

Abstract: In this work we have studied the mechanism for the increase of adrenal ODC (ornithine decarboxylase, EC 4.1.1.17) activity provoked by oxotremorine, a muscarinic agonist. 1. Oxotremorine increased medullary ODC activity maximally at 2 h. Cortical enzyme responded much more slowly. 2. Blockade of peripheral muscarinic receptors with methylatropine partially reduced the response to oxotremorine in the medulla, but not cortex. 3. Hy-pophysectomy abolished the cortical, but not the medullary, responses to oxotremorine. Methylatropine reduced the effect of oxotremorine on medullary ODC in hypophysectomized rats. 4. In unilaterally splanchnicotomized rats oxotremorine caused an increase of ODC activity of the denervated adrenal gland relative to control value; activities in both medulla and cortex were significantly lower than those observed in the innervated gland. Evidence was obtained for a compensatory increase of ODC activity of the adrenal cortex (but not medulla) on the intact side of unilaterally operated rats. 5. Surgical intervention, in the form of a sham operation for transection of the spinal cord, leads to an increase of ODC activity in both parts of the adrenal gland. Transection of the cord attenuates these increases. 6. The additional increase of medullary ODC activity owing to the administration of oxotremorine to sham-operated rats is partially reduced in the adrenal medulla by muscarinic blockade, and completely in the cortex. This effect of methylatropine in regard to cortical ODC activity was not apparent in the other experiments with intact or unilaterally splanchnicotomized (unoperated side) rats. The results with unilaterally splanchnicotomized rats and those with transected spinal cord suggest that oxotremorine-induced modifications of adrenal ODC activity are centrally mediated, above the level of origin of the splanchnic nerves in the spinal cord (T_8–10). Experiments with hypophysectomized rats show that the response of the adrenal cortex to oxotremorine is entirely mediated by the hypophysis.     

Morphology and ultrastructure of the adrenal gland in Bactrian camels (Camelus bactrianus)

In the present study, we examined the morphological features of the adrenal gland in Bactrian camel by means of digital anatomy, light and electron microscopy. Our findings testified that the gland was divided into three parts, capsule, cortex and medulla from outside to inside as other mammals, and the cortex itself was further distinguished into four zones: zona glomerulosa, zona intermedia, zona fasciculate and zona reticularis. Notably, the zona intermedia could be seen clearly in the glands from females and castrated males, whereas it was not morphologically clear in male. There was a great deal of lipid droplets in the zona fasciculate, while it was fewer in the zona glomerulosa and zona reticularis. The cytoplasm of adrenocortical cell contained rich mitochondria and endoplasmic reticulum. The adrenal medulla was well-developed with two separations of external and internal zones. The most obvious histological property of adrenal medulla cells were that they contained a huge number of electron-dense granules enveloped by the membrane, and so medulla cells could be divided into norepinephrine cells and epinephrine cells. Moreover, the cortical cuffs were frequently present in adrenal gland. Results of this study provides a theoretical basis necessary for ongoing investigations on Bactrian camels and their good adaptability in arid and semi-arid circumstances.     

Effects of orexin on cultured porcine adrenal medullary and cortex cells

New orexigenic peptides called orexins have recently been described in the neurons of the lateral hypothalamus and perifornical area. No orexins have been found in the adipose tissues or visceral organs, including the adrenal gland. However, expression of the orexin receptor (OXR) in the rat adrenal gland has been reported. With regard to the effects of orexins on peripheral organs, we previously reported that orexins suppress catecholamine synthesis and secretion in the rat pheochromocytoma cell line PC12. To further clarify the pharmacological effects of orexins on peripheral organs, we examined the effects of orexin-A on catecholamine, cortisol, and aldosterone secretion, using cultured porcine adrenal glands. We initially confirmed the expression of the orexin receptor (OXR-1) in cultured porcine adrenal medulla and cortex. Orexin-A (1000 nM) significantly increased the release of both epinephrine (E) and norepinephrine (NE) from porcine adrenal medullary cells. Similarly, orexin-A (> or = 100 nM) significantly increased the release of both cortisol and aldosterone from porcine adrenal cortex cells. Orexin-A (100 nM) significantly inhibited basal and the PACAP-induced increase in cAMP levels in adrenal medullary cells. Conversely, orexin-A (>o = 100 nM) significantly increased the cAMP level in adrenal cortex cells. These results indicate that orexin-A induces the release of catecholamine from porcine adrenal medullary cells, and aldosterone and cortisol from the cortex cells and has opposite effects on cAMP levels in adrenal medulla and cortex.     

Mechanisms of human adaptation to hypoxia

The effects of adaptation to cold-and-hypoxic exposure on the cardiovascular system, lipid peroxidation and concentrations of adaptogenesis involved hormones were studied in male students. The two weeks cold- and hypoxic training was shown to be accompanied by a significant increase of apnea duration, reduced velocity of bradycardia development and a more rapid ECG post-cold and- hypoxic exposure normalization, as well as by inhibition of activation of adrenal cortex and thyroid gland after stress of different nature. The changes of the character of influences between the indices under study, were demonstrated. The correlation analysis showed an increase of the human's adaptive potential and a decrease of its dependence on the adrenal cortex hormones.     

Neuropeptide W is expressed in the noradrenalin-containing cells in the rat adrenal medulla

Neuropeptide W (NPW) is an endogenous ligand for GPR7, a member of the G-protein-coupled receptor family. NPW plays an important role in the regulation of both feeding and energy metabolism, and is also implicated in modulating responses to an acute inflammatory pain through activation of the hypothalamus-pituitary-adrenal axis. GPR7 mRNA has been shown to be expressed in the hypothalamus, pituitary gland and adrenal cortex. Similarly, NPW expression has been demonstrated in the brain and pituitary gland. However, the precise distribution of NPW-producing cells in the adrenal gland remains unknown. The aim of this study was to explore the distribution and localization of NPW immunoreactivity in the rat adrenal gland. Total RNA was prepared from the hypothalamus, pituitary gland and adrenal gland. RT-PCR revealed the expression of NPW mRNA in these tissues, while in situ hybridization demonstrated the presence of NPW mRNA in the adrenal medulla. When immunohistochemistry was performed on sections of adrenal gland, NPW-like immunoreactivity (NPW-LI) was observed in the medulla but not in the cortex. Moreover, NPW-LI was found to be co-localized in cells which expressed dopamine beta hydroxylase but not phenylethanolamine-N-methyltransferase. The finding that NPW is expressed in noradrenalin-containing cells in the adrenal medulla suggests that it may play an important role in endocrine function in the adrenal gland.     

白暨豚肾上腺的研究

白鱀豚肾上腺重与体重的平均比值为0.25克/公斤,皮质体积与髓质体积的比值为6.59。白鱀豚肾上腺的组织结构与其它海豚相似,它有比较发达的球状带。讨论了白鱀豚肾上腺形态变化在年龄生长、授乳等生理过程和在自然环境、豢养环境生态适应上的意义。并报道了一例罕见的白鱀豚肾上腺先天性表皮样囊肿。       

Detection of the pro-opiomelanocortin peptide fragments--beta-endorphin and ACTH--in the adrenals of rats and mice by immunohistochemistry

Independent peptide fragments of pro-opiomelanocortin molecule, beta-endorphin and ACTH, have been detected immunohistochemically in the adrenal glands of rats and mice. Immunoreactive beta-endorphin and ACTH have been revealed in the adrenal medulla and reticular zone of the adrenal cortex. beta-endorphin and ACTH distribution patterns in adrenal sections were identical, which is indicative of the linked synthesis of these peptides in the adrenal gland. The data obtained suggest the existence of pituitary-independent mechanisms regulating corticosteroidogenesis in the adrenal gland, involving adrenal pro-opiomelanocortin fragments.     

A comparative study on the steroidogenic response due to training and ACTH treatment in the adrenal cortex of the male rat

The aim of this study was to ascertain the effects of training and ACTH administration on the steroidogenic in vitro response in the adrenal cortex of the rat when the tissue was incubated with ACTH. ACTH in vivo treatment resulted in a highly significant increase in the steroidogenic response (P less than 0.001) whereas training as such caused only a slight but insignificant increase in the steroidogenic responsiveness (P greater than 0.05). Training furthermore strongly suppressed the ACTH in vivo induced response (P less than 0.001). ACTH as such revealed the smallest effect on adrenal mass but the biggest effect on the steroidogenic response. It would seem that long term exercise resulted in an overall increase in the mass and size of the adrenal glands by either increasing the size of existing cells or by increasing the number of cells or both. The latter exercise-induced proliferation of adrenal tissue may involve an adaptive mechanism whereby larger total quantities of adrenal tissue of lowered steroidogenic efficiencies (on a mass basis) are produced in order to meet the stress resulting from the training program.     

Identification of aldosterone secretion inhibitory factor in bovine adrenal medulla

We report the first demonstration of an Aldosterone Secretion Inhibitory Factor (ASIF) in acid extracts of bovine adrenal medulla. Following separation from catecholamines and enkephalins, this factor leads to an 80% inhibition of PGE1-stimulated secretion of aldosterone from bovine adrenal zona glomerulosa. ASIF is retained on cation exchange gels and behaves as a small 5K-dalton peptide on Sephadex G-50. This factor cross-reacts in a radio-receptor assay for [125I] atrial natriuretic factor (ANF). ASIF is distinct from all neuropeptides formerly detected in the adrenal medulla, e.g. somatostatin, enkephalin, neuropeptide Y, dynorphin, neurotensin. In the adrenal gland, this ANF-like factor is predominantly found in the medulla (4 pmol/mg protein), with only trace amounts in the cortex (0.1 pmol/mg protein). ASIF might perhaps correspond to the endogenous ligand for the receptor sites that we have previously identified with [125I]ANF in bovine adrenal cortex and could contribute to the formerly reported attenuating influence of the adrenal medulla on mineralocorticoid production.     

Swim training applied at early age is critical to adrenal medulla catecholamine content and to attenuate monosodium L-glutamate-obesity onset in mice

Exercise has been recommended as a remedy against a worldwide obesity epidemic; however, the onset of excessive weight gain is not fully understood, nor are the effects of exercise on body weight control. Activity deficits of the sympathetic nervous system, including the sympathoadrenal axis, have been suggested to contribute to high fat accumulation in obesity. In the present work, swim training was used to observe fat accumulation and adrenal catecholamine stocks in hypothalamic-obese mice produced by neonatal treatment with monosodium L-glutamate (MSG). MSG-treated and normal mice swam for 15 min/day, 3 days a week, from weaning up to 90 days old (EXE 21-90); from weaning up to 50 days old (EXE 21-50) and from 60 up to 90 days old (EXE 60-90). Sedentary MSG and normal mice (SED groups) did not exercise at all. Animals were sacrificed at 90 days of age. MSG treatment induced obesity, demonstrated by a 43.08% increase in epididymal fat pad weight; these adult obese mice presented 27.7% less catecholamine stocks in their adrenal glands than untreated mice (p<0.001). Exercise reduced fat accumulation and increased adrenal catecholamine content in EXE 21-90 groups. These effects were more pronounced in MSG-mice than in normal ones. Halting the exercise (EXE 21-50 groups) still changed fat accretion and catecholamine stocks; however, no effects were recorded in the EXE 60-90 groups. We conclude that metabolic changes imposed by early exercise, leading to an attenuation of MSG-hypothalamic obesity onset, are at least in part due to sympathoadrenal activity modulation.     

Cyclooxygenase-1 and cyclooxygenase-2 expression in rat kidney and adrenal gland after stimulation with systemic lipopolysaccharide

Cyclooxygenase-2 (COX-2) is a recently discovered isoform of cyclooxygenase that is inducible by various types of inflammatory stimuli. Although this enzyme is considered to play a major role in inflammation processes by catalyzing the production of prostaglandins, the precise location, distribution, and regulation of prostaglandin synthesis remains unclear in several tissues. Using in situ hybridization histochemistry, we investigated the induction of COX-1 and COX-2 mRNA expression after systemic administration of a pyrogen, lipopolysaccharide (LPS), in kidney and adrenal gland in the rat. The COX-2 mRNA signals dramatically increased 1 h after LPS treatment in the kidney outer medulla and adrenal cortex, where almost no or little expression was observed in nontreated animals, and returned to control levels within 24 h. COX-2 mRNA levels increased in the kidney inner medulla 6 h after treatment. There was also a significant increase in mRNA levels in the kidney cortex and adrenal medulla. On the other hand, COX-1 mRNA levels did not show any detectable changes except in the kidney inner medulla, where a significant downregulation of mRNA expression was observed after LPS treatment. Light and electron immunocytochemistry using COX-2 antibodies showed that strong COX-2 immunoreactivity was localized to certain cortical cells of the thick ascending limb of Henle. In addition, based on double-staining with antiserum to nitric oxide synthase (NOS) four further cell populations could be identified in kidney cortex, including weakly COX-2-positive, NOS-positive macula densa cells. After LPS treatment, changes in COX-2 immunoreactivity could be observed in interstitial cells in the kidney medulla and in inner cortical cells in the adrenal gland. These results show that COX-2 is a highly induced enzyme that can be up-regulated in specific cell populations in kidney and adrenal gland in response to inflammation, leading to the elevated levels of prostaglandins seen during fever. In contrast COX-1 mRNA levels remained unchanged in this experimental situation, except for a decrease in kidney inner medulla.     

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

Background

Neurofibromatosis type I (NF1, MIM#162200) is a relatively frequent genetic condition, which predisposes to tumor formation. Apart from tumors, individuals with NF1 often exhibit endocrine abnormalities such as precocious puberty (2,5–5% of NF1 patients) and some cases of hypertension (16% of NF1 patients). Several cases of adrenal cortex adenomas have been described in NF1 individuals supporting the notion that neurofibromin might play a role in adrenal cortex homeostasis. However, no experimental data were available to prove this hypothesis.

Materials and Methods

We analysed Nf1Prx1 mice and one case of adrenal cortical hyperplasia in a NF1patient.

Results

In Nf1Prx1 mice Nf1 is inactivated in the developing limbs, head mesenchyme as well as in the adrenal gland cortex, but not the adrenal medulla or brain. We show that adrenal gland size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed deregulation of multiple proteins, including steroidogenic acute regulatory protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol into steroid making mitochondria. This was associated with a marked upregulation of MAPK pathway and a female specific increase of cAMP concentration in murine adrenal lysates. Complementarily, we characterized a patient with neurofibromatosis type I with macronodular adrenal hyperplasia with ACTH-independent cortisol overproduction. Comparison of normal control tissue- and adrenal hyperplasia- derived genomic DNA revealed loss of heterozygosity (LOH) of the wild type NF1 allele, showing that biallelic NF1 gene inactivation occurred in the hyperplastic adrenal gland.

Conclusions

Our data suggest that biallelic loss of Nf1 induces autonomous adrenal hyper-activity. We conclude that Nf1 is involved in the regulation of adrenal cortex function in mice and humans.     

Dopamine in rat adrenal glomerulosa

There is increasing evidence that dopamine (DA) inhibits aldosterone production, but the source of DA for this dopaminergic influence is not known. In the present study we examined the adrenal's zona glomerulosa for the presence of DA. Rats maintained on an intake of regular food were killed by decapitation and the adrenal capsule (containing zona glomerulosa) and the remainder of the gland (containing both cortex and medulla) were examined for their content of DA and also for norepinephrine (NE) and epinephrine (E). DA was found in adrenal glomerulosa in substantial quantity, 1.92 +/- 0.17 (SEM) ng/mg wet weight, representing an approximate concentration of DA of 1-100 microM. DA in adrenal capsule represented 12.2% of the total adrenal content of DA. NE and E were also present in glomerulosa, 3.46 +/- 0.32 and 18.7 +/- 2.1 ng/mg respectively, but, unlike DA, about 98% of the total adrenal content of NE and E was contained in adrenal medulla. The NE/E ratio in capsule and medulla were similar, although slightly higher in adrenal medulla, suggesting that the medulla is the source of the NE and E found in glomerulosa. On the other hand, the DA/E ratio was several-fold higher in glomerulosa than medulla--suggesting that glomerulosa DA was derived at least partially from a source other than adrenal medulla. We also found that short-term culturing of the adrenal reduced DA levels to 1/3 that observed in fresh tissue. This could explain in part why cultured glomerulosa has been shown to be more responsive to administered stimuli. In summary, the findings indicate a significant concentration of DA in adrenal glomerulosa, and suggest that the effects of DA on aldosterone production are mediated locally within the adrenal.     

Neurohypophysial-adrenal gland responses to water-deprivation in the rose-ringed parakeet.

The aim of the present investigation is to study the relative influence of neuohypophysis, adrenal cortex and adrenal medulla under dehydration stress in the parakeet. Birds subjected to dehydration for 7 days lost body weight. Neurosecretory material (NSM) was partially depleted from the neurohypophysis. Adrenal gland weight was increased followed by a hypertrophy of the cortical tissue. A fall in adrenal cholesterol and ascorbic acid level was marked. Adrenaline and noradrenaline contents of the adrenal medulla were suppressed as was evident from cytochemical and biochemical findings. It is suggested that neurohypophysis, adrenal cortex and adrenal medulla are involved in maintaining water homeostasis in this avian species.     

Identification of pro-opiomelanocortin and the secretion of its peptide fragments in the adrenals of the bull

Immunoreactive alpha-, beta- and gamma-endorphins and beta-lipotropin--C-terminal peptide fragments of pro-opiomelanocortin (POMC)--were discovered and measured by RIA in the bovine adrenal medulla and cortex. These peptides were also discovered in perfusates of the adrenal gland. POMC proper and some intermediate forms of its processing not differing in electrophoretic mobility from the respective molecular forms of hypophyseal POMC were identified in the medulla and cortex of the adrenals by the immunoblotting technique with the use of antiserum to beta-lipoprotein. It is concluded that POMC gene is expressed in the adrenal medulla and cortex and that as a result of POMC processing a noticeable amount of its peptide fragments is formed and secreted in adrenal cells. The authors thus suggest the presence of existence of the pituitary-unrelated mechanisms of adrenal function control with participation of POMC peptides synthesized in the adrenals.