Long-term salt loading impairs pituitary responsiveness to ACTH secretagogues and stress in rats

Male Wistar rats were allowed to drink tap water ad lib (W), 2% saline (S) or 2% saline containing dexamethasone (S + D, 1 mg/l) for 7 days. On the 8th day rats were subjected to a 3-min ether stress. Plasma ACTH, corticosterone and prolactin concentrations were determined before and after ether exposure. Prestress concentrations of plasma ACTH were low and did not vary among the three groups. In response to ether stress W rats exhibited twice as high plasma ACTH concentrations as did S rats. Rats of the S + D group exhibited a small but statistically significant ACTH response. Plasma corticosterone concentration in S rats was increased while in S + D rats was significantly decreased under resting conditions compared to that in W rats. Ether stress caused large increases in plasma corticosterone concentrations in W and S rats while a small but statistically significant increase was observed in S + D rats. Prolactin responses to ether were smaller in groups S and S + D than in group W. To test whether the decreased ACTH response to ether exposure was a result of a decreased sensitivity of corticotrope cells to corticotropin releasing factor (CRF)-41 or arginine vasopressin (AVP), adenohypophysial fragments from W, S and S + D rats were incubated in the presence of different doses of CRF-41 or AVP. Pituitary fragments obtained from W rats secreted larger amounts of ACTH than did pituitaries from S rats in response to either CRF-41 or AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of short- and long-term diabetes on carnitine and myo-inositol in rats.

1. The effect of short- (2 wk) and long-term (20 wk) streptozotocin diabetes was studied on urine, blood, liver, heart, brain, skeletal muscle, pancreas and kidney concentrations of acid-soluble carnitine and free myo-inositol. 2. Short-term diabetic rats excreted significantly higher concentrations of carnitine as well as myoinositol than normal rats. Blood carnitine and myo-inositol were not different between normal and diabetic rats. Diabetes caused a decrease in liver, brain and pancreatic carnitine, but not in heart, skeletal muscle and kidney. Myo-inositol concentration was decreased in liver, heart and kidney but not in brain, pancreas and skeletal muscle. 3. Long-term diabetic rats had higher urinary excretions of both carnitine and myo-inositol. Blood carnitine did not change; however, myo-inositol was higher in diabetic than in normal rats. Diabetes caused a significant increase in liver and a decrease in heart, brain, skeletal muscle and pancreatic content of carnitine; no difference in kidney carnitine was noted. Myo-inositol content was elevated only in liver of diabetic rats. 4. We suggest that carnitine and myo-inositol concentrations are influenced both by short- and long-term diabetes through changes in tissue metabolism.     

Vertebrate salt glands: short- and long-term regulation of function

Excess salt loads in most non-mammalian vertebrates are dealt with by a variety of extra-renal salt-secreting structures collectively described as salt glands. The best studied of these are the supra-orbital nasal salt glands of birds. Two distinct types of response to osmoregulatory disturbances are shown by this structure: a progressive adaptive response on initial exposure to a salt load that results in the induction and enhancement of the secretory performance or capabilities of the gland; and the rapid activation of existing osmoregulatory mechanisms in the adapted gland in response to immediate osmoregulatory imbalance. Not only is the time-frame of these two types of response very different, but the responses usually involve fundamentally different processes: e.g., the growth and differentiation of osmoregulatory structures and their components in the former case, compared with the rapid activation of ion channels, pumps etc. in the latter. Despite marked differences in the nature and time-frame of these responses, they both are apparently triggered by neuronally released acetylcholine, which acts at muscarinic receptors on the secretory cells to induce an inositol phosphate-dependent increase in cytosolic-free calcium concentrations ([Ca2+]i). Therefore, the question arises as to how the cells produce the appropriate distinct response using a single common signal (i.e., an increase in [Ca2+]i). Examination of the features of this signaling pathway in the two conditions described, reveals that they each are uniquely tuned to generate a response with the characteristics appropriate for the cells' requirements. This tuning of the signal involves often rather subtle changes in the overall signaling pathway that are part of the adaptive differentiation process.     

Guar gum consumption in adolescent and adult rats: short- and long-term metabolic effects

Metabolic responses to short- and long-term guar gum consumption were studied in adolescent and adult rats. For the long-term study, male adolescent rats were divided into four groups (n = 60/group) and fed guar gum, cellulose, or bran diet for 67 weeks. Metabolic studies (food--water intake, feces--urine output, body weight, carbohydrate tolerance) were performed eight times during the 67 weeks. The guar gum group consumed less diet throughout the entire study and gained less weight over the first 20 weeks compared with the cellulose and bran groups. A second bran-fed group was food restricted over the first 20 weeks to match the reduced weight gain of the guar gum group and then fed ad libitum. Reduced plasma glucose excursions were measured for only the guar gum group after both fibre-free glucose and sucrose challenges at weeks 6, 12, and 18; from 24 to 64 weeks all four groups had similar glucose tolerance responses. Twenty-four hour urinary glucose excretion was similar during all eight metabolic studies up to 64 weeks for guar gum and cellulose groups. In the short-term study, male adolescent (200 g; n = 10/group) and adult (630 g; n = 15/group) rats were divided into five and four groups, respectively, and fed guar gum, guar by-product (GBP), cellulose, or bran diet for 6 weeks. A metabolic study was performed during the 6th week. Adolescent rats fed guar gum or GBP diets gained less weight than the cellulose group; only the guar gum group displayed improved carbohydrate tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of short- and long-term high-fat diet feeding on hepatic fatty acid metabolism in rats

Imbalance in the supply and utilization of fatty acids (FA) is thought to contribute to intrahepatic lipid (IHL) accumulation in obesity. The aim of this study was to determine the time course of changes in the liver capacity to oxidize and store FA in response to high-fat diet (HFD). Adult male Wistar rats were fed either normal chow or HFD for 2.5weeks (short-term) and 25weeks (long-term). Short-term HFD feeding led to a 10% higher palmitoyl-l-carnitine-driven ADP-stimulated (state 3) oxygen consumption rate in isolated liver mitochondria indicating up-regulation of β-oxidation. This adaptation was insufficient to cope with the dietary FA overload, as indicated by accumulation of long-chain acylcarnitines, depletion of free carnitine and increase in FA content in the liver, reflecting IHL accumulation. The latter was confirmed by in vivo((1))H magnetic resonance spectroscopy and Oil Red O staining. Long-term HFD feeding caused further up-regulation of mitochondrial β-oxidation (24% higher oxygen consumption rate in state 3 with palmitoyl-l-carnitine as substrate) and stimulation of mitochondrial biogenesis as indicated by 62% higher mitochondrial DNA copy number compared to controls. These adaptations were paralleled by a partial restoration of free carnitine levels and a decrease in long-chain acylcarnitine content. Nevertheless, there was a further increase in IHL content, accompanied by accumulation of lipid peroxidation and protein oxidation products. In conclusion, partially effective adaption of hepatic FA metabolism to long-term HFD feeding came at a price of increased oxidative stress, caused by a combination of higher FA oxidation capacity and oversupply of FA.     

Ethanol dependence and the pituitary adrenal axis in mice II. Temporal analysis of dependence and withdrawal.

The effects of ethanol dependence and withdrawal on pituitary hormone content and corticosterone release were investigated in AKR/J male mice in a vapor chamber. Both chronic ethanol inhalation and ethanol withdrawal were associated with increased adenohypophyseal-adrenocortical activity. Operationally, ethanol exposure was a stressor. Both physical dependence and withdrawal led to increased secretion/synthesis ratios of peptide hormones. The temporal pattern of pituitary ACTH-IR content changes was different from that of β-endorphin-IR and α-MSH-IR. Differences in the pattern of ACTH-IR and α-MSH-IR most probably represent lobe-specific differences in the response to chronic ethanol exposure and withdrawal.     

The effects of long-term nitrogen loading on grassland insect communities

Just as long-term nitrogen loading of grasslands decreases plant species richness and increases plant biomass, we have found that nitrogen loading decreases insect species richness and increases insect abundances. We sampled 54 plots that had been maintained at various rates of nitrogen addition for 14 years. Total insect species richness and effective insect diversity, as well as herbivore and predator species richness, were significantly, negatively related to the rate of nitrogen addition. However, there was variation in trophic responses to nitrogen. Detritivore species richness increased as nitrogen addition increased, and parasitoids showed no response. Insect abundances, measured as the number of insects and insect biovolume (an estimate of biomass), were significantly, positively related to the rate of nitrogen addition, as were the abundances of herbivores and detritivores. Parasitoid abundance was negatively related to the rate of nitrogen addition. Changes in the insect community were correlated with changes in the plant community. As rates of nitrogen addition increased, plant species richness decreased, plant productivity and plant tissue nitrogen increased, and plant composition shifted from C₄ to C₃ grass species. Along this gradient, total insect species richness and effective insect diversity were most strongly, positively correlated with plant species richness. Insect biovolume was negatively correlated with plant species richness. Responses of individual herbivores varied along the nitrogen gradient, but numbers of 13 of the 18 most abundant herbivores were positively correlated with their host plant biomass. Although insect communities did not respond as strongly as plant communities, insect species richness, abundance, and composition were impacted by nitrogen addition. This study demonstrates that long-term nitrogen loading affects the entire food chain, simplifying both plant and insect communities. Received: 18 May 1999 / Accepted: 5 January 2000     

Metabolism of glomerular basement membrane in short- and long-term streptozotocin diabetic rats

The synthesis of glomerular basement membrane (GBM) total protein and collagen was assessed by two methods in vivo in normal and streptozotocin diabetic rats 4-6 weeks and 42-44 weeks after onset of hyperglycaemia, using L-[2, 3, 3H] proline as a radioactive precursor. The incorporation of tritiated proline into GBM hydroxyproline was used as a measure of collagen synthesis and that into proline as total protein synthesis. The basement membrane fractions from both short- and long-term diabetic rats attained much higher proline and hydroxyproline specific activities compared to normal GBM proline and hydroxyproline specific activities. Early insulin therapy with normalization of blood sugar levels in short-term (4-6 weeks) diabetic rats returned the abnormal increases in GBM total protein and collagen synthesis to normal. By contrast, poor glycaemic control with insulin did not prevent the increases in GBM protein synthesis. The results of the present study suggest that overall enhancement of GBM protein synthesis occurs in both short- and long-term streptozotocin diabetes. Early insulin therapy with normalization of blood sugar levels prevents this increase in GBM protein synthesis. Poor glycaemic control had no effect on abnormal GBM protein synthesis. This may be of potential significance in view of preventing chronic diabetic microvascular complications such as nephropathy.     

Type VI collagen in glomeruli of short- and long-term experimental diabetic rats

Type VI collagen was revealed by high-resolution immunocytochemistry in renal glomeruli from short- and long-term streptozotocin-injected hyperglycaemic rats and from their age-matched normoglycaemic controls. The labellings obtained over the glomerular basement membrane and the mesangial matrix were assessed by quantitative evaluations. The labellings over the glomerular basement membrane were low and sparse in the young normoglycaemic animals but became consistent and increased in intensity with age and in both the short- and long-term diabetic animals. For the mesangial matrix, this was labelled more systematically, and its intensity increased with age and in the short-term hyperglycaemic animals. For the long-term hyperglycaemic animals, the intensities of labelling resembled those of their age-matched controls. These results indicate that type VI collagen appears to be a minor constituent of the extracellular matrix of the rat glomeruli, rather concentrated in the mesangial area in the young control animal. Concomitant with the general modifications of the extracellular matrix occurring with age and diabetes, this component increases, but apparently not with the length of the hyperglycaemic state. © Chapman & Hall     

Effects of intraventricular norepinephrine on LH release in short- and long-term ovariectomized steroids-primed rats

This study examined the noradrenergic mechanism in regulation of luteinizing hormone (LH) release in short- and long-term ovariectomized (OVX) steroids-primed rats. All rats were OVX on the diestrous day 1(D1) morning about 1000 h. After OVX, rats in the short-term OVX group were immediately primed with estradiol (E2, 0.1 mg/kg BW s.c.), fitted with atrial Silastic tubing, and a guide cannula in the right lateral cerebroventricle stereotaxically. Rats in the long-term OVX group received the same treatment (E2, atrial tubing and guide cannula implantation) three weeks later. Rats in both groups received progesterone (2 mg/rat s.c.) at 0930 h on the next day after E2. At 1000 h, intraventricular administration of norepinephrine HCl (NE, 0.01, 0.1, or 1.0 microgram in 2 microliters saline) was given. In short-term OVX-steroids-primed rats, NE did not alter LH levels in the peripheral plasma within 60 or 100 min. By contrast, in long-term OVX-steroids-primed rats, 1.0 microgram of NE gradually decreased plasma LH concentrations, which became significantly different from the initial value at the 60 min time point after treatment. On the other hand, intraventricular injection of 5 ng of the LH-releasing hormone (LHRH) elevated plasma LH concentrations within 10 min in both groups of rats, but at different efficacy: a brief release of LH in short-term OVX-steroids-primed rats and a prolonged release of LH in long-term OVX-steroids-primed rats. These results indicated that the interval after OVX plays a critical role in modulating the responsiveness to NE and LHRH in the steroids-primed OVX rats.     

Influence of cyclooxygenase inhibitors on the central histaminergic stimulations of hypothalamic - pituitary - adrenal axis.

Brain histamine participates in central regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Endogenous prostaglandins modulate signal transduction of different neurotransmitters involved in activation of HPA axis. In the present experiment we investigated whether endogenous prostaglandins are involved in the stimulation of ACTH and corticosterone secretion by histaminergic systems in the rat brain. Histamine (50 microg), histamine-trifluoromethyl-toluidine derivative (HTMT, 75microg) a selective and potent H(1)-receptor agonist, and amthamine (50 microg) a H(2)-receptor agonist given intracerebroventricularly (i.c.v.) to non-anesthetized rats considerably increased ACTH and corticosterone secretion 1h after administration. A non-selective cyclooxygenase inhibitor indomethacin (2 mg/kg i.p. or 10 microg i.c.v.), piroxicam (0.02 and 0.2 microg i.c.v.) a more potent antagonist of constitutive cyclooxygenase (COX-1) and compound NS-398 (0.1 and 1.0 microg i.c.v.), a selective inhibitor of inducible cyclooxygenase (COX-2) were given 15 min before histamine and histamine receptor agonists. One hour after the last injection trunk blood from decapitated rats was collected for hormones determination. The histamine-induced ACTH and corticosterone secretion was significantly diminished by piroxicam and was not markedly altered by indomethacin and compound NS-398. The HTMT-elicited increase in ACTH and corticosterone secretion was significantly prevented by indomethacin and was not affected by piroxicam or compound NS-398. The amthamine-evoked increase in ACTH and corticosterone secretion was not markedly influenced by any cyclooxygenase blocker applied in the present experiment. These results indicate that the histamine H(1)-receptor transmitted central stimulation of the HPA axis is considerably mediated by prostaglandins generated by consititutive cyclooxygenase, whereas stimulation transmitted via H(2)-receptor does not significantly depend on endogenous prostaglandins mediation.     

The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis

Type 1 diabetes is an autoimmune disorder characterized by a lack of insulin production by the beta cells of the pancreas. This lack of insulin causes a variety of systemic effects on whole-body metabolism. Poorly managed type 1 diabetes can lead to cardiovascular disease, diabetic neuropathy, and diabetic retinopathy. Increasingly, even well-managed type 1 diabetic patients show damage to peripheral organs related to complications from the disease. The central role of insulin in energy homeostasis also renders it an important signaling factor in the reproductive tract. type 1 diabetes has now been demonstrated to cause defects in sperm and testes. The aim of this review is to present the known effects of insulin's role in the function of the male reproductive tract. These effects might be mediated through hormonal alterations in the hypothalamic pituitary gonadal axis or through the direct interaction of insulin on the testes and sperm cells. Although fertility complications also occur in type 2 diabetic males, this review will focus on the defects specifically linked with the lack of insulin seen in type 1 diabetes.     

Critical role of the hypothalamic pituitary adrenal axis in amphetamine-induced sensitization of behavior

Behavioral sensitization can be observed with repeated administration of amphetamine where the intensity of motor stimulation increases over time. The process of sensitization has been well characterized, however, the neurochemical mechanisms that are critical for the development of sensitization are not known. In the present study, the role of the hypothalamic pituitary adrenal axis (HPA) in the development of behavioral sensitization to amphetamine was explored by pretreating rats with an intravenous administration of an antiserum to corticotropin-releasing factor in a volume that has been shown to block significantly stress- and cocaine-induced activation of the HPA. Four groups of eight rats were pretreated intravenously with either heparinized saline or CRF antiserum and subcutaneously with saline or d-amphetamine in a balanced design. The rats were then returned to their home cages and left undisturbed for seven days after which they were given three consecutive behavioral tests with saline SC, 0.75 mg/kg d-amphetamine SC, and 3.0 mg/kg d-amphetamine SC. The rats pretreated with intravenous CRF antiserum showed a significant attenuation of the development of d-amphetamine-induced sensitization but the antiserum did not alter the magnitude of the behavioral response to the initial, sensitizing dose of d-amphetamine. These results suggest that activation of the hypothalamic pituitary adrenal axis may be of critical importance to the development of behavioral sensitization to amphetamine.     

Ischemia induces short- and long-term remodeling of synaptic activity in the hippocampus

One of the most vulnerable areas to ischemia or hypoglycemia is CA1 hippocampal region due to pyramidal neurons death. Glutamate receptors are involved together with protein-kinase C and nitric oxide synthase. Long-term potentiation (LTP) is generated in anoxic or hypoglycemic conditions via activation of NMDA while inhibition of these receptors atenuates this response. Protein-kinase C and nitric oxide synthase are involved in anoxic LTP mechanism. Postischemic neurons are hyperexcitable in CA3 area while CA1 pyramidal neurons degenerate and dissapear. Changes of glutamate receptors triggered by ischemia and hypoglycemia are discussed in this review.     

Analysis of short- and long-term effects of adaptation in human postural control

 The short-term (i.e., days) and long-term (i.e., months) effects of adaptation to posturography examinations were investigated in 12 normal subjects who were repeatedly examined for five consecutive days and again after 90 days. The examinations were conducted both with eyes open and closed, and the perturbations were evoked by a pseudorandomly applied vibration stimulation to the calf muscles. The evoked anteroposterior responses were analyzed with a method considering adaptation in the slow changes in posture and in the stimulus–response relationship. Repetition of examinations on a daily basis revealed a gradual improvement of postural-control performance. The body sway induced by the stimulation was significantly reduced and the dynamical properties changed. Most of the improvements remained after 90 days, but some parameters such as the complexity of the control system used were increased to the initial level. The results confirm previous observations that postural control contains several partially independent adaptive processes, observed in terms of alteration of posture and as a progressive reduction of body sway induced by stimulation. The method used for the adaptation analysis in this study could be applied to analyze biological systems with multiple individual adaptive processes with different time courses or characteristics, or where the adaptation processes are related to multiple internal or external factors. Received: 2 January 2001 / Accepted in revised form: 27 November 2001     

Exploration of the human fetal pituitary adrenal axis: stimulation of cortisol and dehydroepiandrosterone sulfate biosynthesis by homologous pituitary in organ culture.

Adrenals obtained from human abortices at midpregnancy were kept under conditions of tissue culture and the production of cortisol and dehydroepiandrosterone sulfate (3beta-hydroxy-5-androsten-17-one, 3-sulfate; DHA-S) monitored by radioimmunoassays for up to 2 weeks. Basal production of dehydroepiandrosterone sulfate was considerably higher than that of cortisol. alpha1-24corticotrophin, alpha1-39corticotrophin, (a long acting porcine corticotrophin) at the concentration of 1 mU/ml of culture medium in both instances, and dibutyryl cyclic AMP (1mM) enhanced the production of both steroids some 3 to 30 times above control values. Medium harvested from homologous pituitary cultures had comparable corticotrophic activity. It is concluded that at midpregnancy the regulation of corticoidogenesis implies the existence of a corticotrophic factor either identical or closely related to ACTH.