Effects of hormones on the synthesis of α1 (acute-phase) glycoprotein in isolated rat hepatocytes

Hormone effects on the synthesis of alpha(1) (acute-phase) glycoprotein and of albumin by isolated rat hepatocytes in suspension were examined. Insulin, glucagon, cortisol, somatotropin (bovine growth hormone) and tri-iodothyronine were added to achieve physiological concentrations in the medium [Jeejeebhoy, Ho, Greenberg, Phillips, Bruce-Robertson & Sodtke (1975) Biochem. J.146, 141-155]. After periodic additions, there were increases (compared with values for non-hormone-treated suspensions) in the concurrent absolute syntheses of alpha(1) (acute-phase) glycoprotein and of albumin. Trends were detectable after 24h, and significant increases were demonstrated after 48h of incubation (219 and 119% respectively of control values). Manipulation of hormones, by omission from the mixture or by addition of only one or two hormones in various combinations, indicated that for alpha(1) (acute-phase) glycoprotein (which may be representative of some other acute-phase proteins), cortisol was one of the most important hormones involved in the stimulation of synthesis, with glucagon enhancing the effect of cortisol but not being stimulatory by itself. Addition of actinomycin D inhibited this stimulation, suggesting that cortisol might have acted through promotion of RNA synthesis. For albumin, cortisol alone did not stimulate synthesis, but its absence from a hormone mixture significantly decreased synthesis compared with that observed with the complete hormone mixture. Our findings support the possibility that following tissue injury, synthesis of alpha(1) (acute-phase) glycoprotein may be stimulated by the hormonal response to this injury (which response includes elevated blood concentrations of cortisol and glucagon).     

Inhibition of compensatory renal growth by indomethacin

Renal prostaglandins may be important in the modulation of compensatory renal growth. Reductions in renal mass are associated with increased synthesis of these substances by the remaining kidney, and inhibition of prostaglandin synthesis diminishes renal function in partially nephrectomized animals and in patients with reduced functioning renal mass. We examined the effects of uninephrectomy and treatment with indomethacin on renal prostaglandin E2 and 6-keto prostaglandin F1 alpha concentrations in adult male Sprague Dawley rats. The renal content of these prostaglandins was significantly increased in the remaining kidney two days following uninephrectomy (p less than 0.01). Treatment with 5 mg/kg/day of indomethacin over this period abolished the compensatory increase in renal prostaglandin synthesis and significantly attenuated compensatory increases in renal mass, protein and RNA concentrations (p less than 0.05). No alterations in kidney weight, protein or RNA concentrations were found in intact animals treated with the same dose of indomethacin. These findings suggest renal prostaglandins may participate in the biological events leading to compensatory renal growth.     

Effects of pretreatment with adrenocorticotropin on endocrine and behavioral responses of bulls to sexual activity

Peripheral concentrations of cortisol, growth hormone and testosterone were determined in two experiments which examined the endocrine and behavioral responses of sexually mature Angus bulls to an estrous female (Experiment 1) and to female exposure 5 hours following an adrenocorticotropin (ACTH) injection (Experiment 2). Sexual activity of bulls in Experiment 1 significantly increased levels of cortisol when compared with concentrations before exposure to a female. Administration of ACTH in Experiment 2 consistently elevated levels of cortisol by 30-fold (P<0.01) when compared with pre-ACTH concentrations. This heightened level of cortisol persisted throughout the period of exposure to an estrous cow, although a gradual decline in cortisol concentrations occurred over time (P<0.05). In Experiment 1, growth hormone profiles tended to increase in response to sexual activity (P<0.10), whereas in Experiment 2, growth hormone increased in response to ACTH administration (P<0.01) and to female exposure (P<0.01). Concentrations of testosterone were unaffected (P>0.10) by mating activity in Experiment 1. In Experiment 2, acute suppression (P<0.01) in testosterone concentrations 5 hours after ACTH administration coincided with the exposure period to the estrous female. Frequencies of mounting behavious (penis extension, mounting, intromission and ejaculation) exhibited by ACTH-treated bulls were significantly lower compared with the frequencies two days earlier. Exogenous ACTH administration suppressed reproductive behaviors of bulls and altered secretion of cortisol, growth hormone and testosterone. Furthermore, these data provide evidence that specific mating behaviors of the bull can be influenced by circulating steroids.     

Indomethacin does not affect endogenous glucose production in type 2 diabetes mellitus.

In healthy subjects, basal endogenous glucose production is partly regulated by paracrine intrahepatic factors. It is currently unknown whether paracrine intrahepatic factors also influence the increased basal endogenous glucose production in patients with type 2 diabetes mellitus. Administration of indomethacin to patients with type 2 diabetes mellitus stimulates endogenous glucose production and inhibits insulin secretion. Our aim was to evaluate whether this stimulatory effect on glucose production is solely attributable to inhibition of insulin secretion. In order to do this, we administered indomethacin to 5 patients with type 2 diabetes during continuous infusion of somatostatin to block endogenous insulin and glucagon secretion and infusion of basal concentrations of insulin and glucagon in a placebo-controlled study. Endogenous glucose production was measured 3 hours after the start of the somatostatin, insulin and glucagon infusion, for 4 hours after administration of placebo/indomethacin, by primed, continuous infusion of [6,6-(2)H(2)] glucose. At the time of administration of placebo or indomethacin, there were no significant differences in plasma glucose concentrations and endogenous glucose production rates between the two experiments (16.4 +/- 2.09 mmol/l vs. 16.6 +/- 1.34 mmol/l and 17.7 +/- 1.05 micromol/kg/min and 17.0 +/- 1.06 micromol/kg/min), control vs. indomethacin). Plasma glucose concentration did not change significantly in the four hours after indomethacin or placebo administration. Endogenous glucose production in both experiments was similar after both placebo and indomethacin. Mean plasma C-peptide concentrations were all below the detection limit of the assay, reflecting adequate suppression of endogenous insulin secretion by somatostatin. There were no differences in plasma concentrations of insulin (76 +/- 5 vs. 74 +/- 4 pmol/l) and glucagon (69 +/- 8 vs. 71 +/- 6 ng/l) between the studies with levels remaining unchanged in both experiments. Plasma concentrations of cortisol, epinephrine, and norepinephrine were similar in the two studies and did not change significantly. We conclude that indomethacin stimulates endogenous glucose production in patients with type 2 diabetes mellitus by inhibition of insulin secretion.     

Inhibition of compensatory renal growth by indomethacin

Renal prostaglandins may be important in the modulation of compensatory renal growth. Reductions in renal mass are associated with increased synthesis of these substances by the remaining kidney, and inhibition of prostaglandin synthesis diminishes renal function in partially nephrectomized animals and in patients with reduced functioning renal mass. We examined the effects of uninephrectomy and treatment with indomethacin on renal prostaglandin E₂ and 6-keto prostaglandin F_1α concentrations in adult male Sprague Dawley rats. The renal content of these prostaglandins was significantly increased in the remaining kidney two days following uninephrectomy (p<0.01). Treatment with 5 mg/kg/day of indomethacin over this period abolished the compensatory increase in renal prostaglandin synthesis and significantly attenuated compensatory increases in renal mass, protein and RNA concentration (p<0.05). No alterations in kidney weight, protein or RNA concentrations were found in intact animals treated with the same dose of indomethacin. These findings suggest renal prostaglandins may participate in the biological events leading to compensatory renal growth.     

The effects of dietary vitamin C on growth,liver vitamin C and serum cortisol in stressed and unstressed juvenile soft-shelled turtles (Pelodiscus sinensis)

We studied the effect of dietary vitamin C on growth, liver vitamin C and serum cortisol levels in stressed and unstressed juvenile soft-shelled turtles. Turtles were fed with vitamin C supplementation at dosages of 0, 250, 500, 2500, 5,000 or 10,000 mg/kg diet for 4 weeks. Vitamin C supplementation exerted significant effects on specific growth rate and liver vitamin C concentrations. The specific growth rate peaked in the group fed at 500 mg/kg diet, while liver vitamin C levels increased with increasing dietary vitamin C levels. Serum cortisol concentrations did not differ between groups of turtles fed diets supplemented with vitamin C in the range of 0-10,000 mg/kg. After acid stress, hepatic vitamin C levels were unaffected, while serum cortisol in the control group was significantly elevated (P<0.01). The other five groups of turtles did not show significant changes in serum cortisol compared with pre-stress levels.     

The IGF-1/cortisol ratio as a useful marker for monitoring training in young boxers

Training effects on plasma insulin-like growth factor-1 (IGF-1)/cortisol ratio were investigated in boxers. Thirty subjects were assigned to either the training or the control group (n = 15 in both). They were tested before the beginning of training (T0), after 5 weeks of intensive training (T1), and after 1 week of tapering (T2). Physical performances (Yo-Yo intermittent recovery test level-1), training loads, and blood sampling were obtained at T0, T1, and T2. Controls were only tested for biochemical and anthropometric parameters at T0 and T2. A significantly higher physical performance was observed at T2 compared to T1. At T1, cortisol levels were significantly increased whereas IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels remained unchanged compared to baseline. At T2, cortisol levels decreased while IGF-1 and IGFBP-3 levels increased. The IGF-1/cortisol ratio decreased significantly at T1 and increased at T2, and its variations were significantly correlated with changes in training loads and Yo-Yo intermittent recovery test level 1 (IRT1) performance over the training period. Cortisol variations correlated with changes in training load (r = 0.64; p < 0.01) and Yo-Yo IRT1 performance (r = 0.78; p < 0.001) at T1 whereas IGF-1 variations correlated only with changes in Yo-Yo IRT1 performance at T2 (r = 0.71; p < 0.001). It is concluded that IGF-1/cortisol ratio could be a useful tool for monitoring training loads in young trained boxers.     

Neuroendocrine and behavioral effects of m-chlorophenylpiperazine administration in rhesus monkeys

The effects of m-chlorophenylpiperazine (mCPP), a serotonin receptor agonist, on the release of plasma prolactin (PRL), growth hormone (GH), and cortisol in the rhesus monkey were studied. mCPP was administered intravenously at doses of 0.5, 1.5, and 3.0 mg/kg. GH and cortisol were increased significantly at all doses whike PRL was significantly increased only following administration of 3.0 mg/kg mCPP. mCPP administration also produced behavioral alterations in each monkey, including sedation, penile erection, and defecation. PRL, GH and behavioral responses to mCPP were completely blocked by pretreatment with the serotonin anatgonist metergoline (MTG). However, pretreatment with MTG failed to entirely antagonize the cortisol response to mCPP. These data suggest that mCPP has prominent neuroendocrine and behavioral effects which are mediated, in part, by serotonergic mechanisms.     

Indomethacin Inhibits Endothelial Cell Proliferation by Suppressing Cell Cycle Proteins and PRB Phosphorylation: A Key to Its Antiangiogenic Action?

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit angiogenesis in vivo and in vitro, but the mechanism of this action is unclear. Angiogenesis—formation of new capillary vessels—requires endothelial proliferation, migration, and tube formation. It is stimulated by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The cell cycle is regulated positively by cyclins and negatively by cyclin-dependent kinase inhibitors (CKI) and the retinoblastoma protein (pRb). Since the effects of NSAIDs on cell cycle-regulatory proteins in endothelial cells remain unknown, we examined the effect of indomethacin on bFGF-stimulated endothelial cell proliferation and on cell cycle regulatory proteins in rat primary aortic endothelial cells (RAEC). Indomethacin significantly inhibited basal and bFGF-stimulated endothelial cell proliferation. This inhibition correlated significantly with reduced cyclin D1 and increased p21 protein expression. Furthermore, indomethacin reduced pRb phosphorylation. These findings suggest that indomethacin arrests endothelial cell proliferation essential for angiogenesis by modulating cell cycle protein levels.     

Induction by cortisol of aminopeptidases production from the human placenta in tissue culture.

Human placental aminopeptidase M and A and post-proline endopeptidase are known to act as degrading enzymes of bioactive peptides such as angiotensin II, oxytocin and endogenous opioids. We tested the effects of cortisol on the activities of human placental aminopeptidase A and M and post-proline endopeptidase using short-cultured placental tissues. From 34.5 nM to 3.45 microM of cortisol significantly increased the activities of 3 enzymes. Our present data suggest a possible important role of cortisol in the growth of human placenta via induction of placental aminopeptidases.     

The effects of cortisol and testosterone on renal function in male Antechinus stuartii (Marsupialia)

Seasonal changes in the physiology of Antechinus stuartii result in complete male mortality after mating. The most important endocrine changes in males are large rises in plasma testosterone and cortisol concentrations. Glomerular filtration rate (GFR) in males declines coincident with high plasma testosterone and cortisol. In the present study GFRs were measured in males captured in May (when endogenous plasma testosterone and cortisol levels are low) and given depot injections of either saline, testosterone-only, cortisol-only or testosterone plus cortisol at doses designed to mimic plasma levels during the mating period. GFR decreased significantly with testosterone injection, independent of cortisol treatment. Urinary concentrations of sodium and chloride, and osmolality decreased significantly with cortisol treatment, although the addition of testosterone reversed the effect. Total urinary excretion of electrolytes was similar between groups. Plasma potassium levels significantly increased in testosterone plus cortisol treated males. Plasma sodium levels significantly increased and plasma chloride significantly decreased in all groups treated with cortisol. Water consumption significantly increased in all cortisol-treated males and food consumption significantly increased in all testosterone-treated males. The seasonal renal functional changes observed in A. stuartii were mimicked by testosterone administration. Accepted: 23 January 1998     

维生素E对中华鳖幼鳖生长、肝脏维生素E以及血清皮质醇含量的影响

为探讨维生素E(VE)对中华鳖(Pelodiscus sinensis)幼鳖的生长、肝脏VE和血清皮质醇的影响，通过特定生长率、高压液相色谱法和放免法，我们测定了中华鳖幼鳖的生长、肝脏VE和血清皮质醇含量。发现VE添加量为1000和5000mg／kg的两组，能明显降低中华鳖幼鳖的生长。维生素E添加量为500、1000和5000mg／kg的三组，肝脏维生素E含量明显高于对照组，VE添加量在0—1000mg／kg的范围时，肝脏VE的含量随着饲料中VE含量的增加呈指数式增加，并且在VE添加量为5000kg／kg的一组基本达到饱和。维生素E添加量为0和50mg／kg的2组，其血清皮质醇的平均值明显高于维生素E添加量为250、500、1000和5000mg／kg的4组的平均值。上述结果表明：高剂量的VE降低了中华鳖幼鳖的生长和血清皮质醇的含量；在一定剂量范围内，肝脏VE随着饲料中VE含量的增加而升高。     

The role of glucocorticoids in healing of indomethacin-induced lesions in the rat gastric mucosa

Pretreatment with a single large dose of cortisol a week before indomethacin administration, or an adrenalectomy induced a glucocorticoid production deficiency in rats. The area of gastric erosions in these rats was considerably larger than in the control animals in 4, 24, and 48 hours after the indomethacin administration. Administration of corticosterone noticeably prompted the healing of the erosions in the rats with glucocorticoid deficiency. The findings suggest a gastroprotective effect of glucocorticoids in healing of indomethacin-induced mucosal injury.     

Effect of TGF-Alpha on growth of normal human breast epithelial cells in serum-free primary culture using 3-dimensional collagen gels.

The mitogenic effect of TGF-alpha, acidic-FGF, basic-FGF and lithium on normal human breast epithelial cells was studied in a collagen gel culture system using a serum-free 1:1 mixture of Ham's F12 and DME medium containing insulin, cholera toxin and bovine serum albumin. TGF-alpha elicited a strong mitogenic response in a dose dependent manner. Addition of cortisol to TGF-alpha stimulated growth over and above that achieved with TGF-alpha alone. A consistent observation has been the effect of a combination of TGF-alpha and cortisol on growth stimulation of normal human breast epithelial cells resulting in 3-12 fold growth after 11-13 days in culture. Acidic-FGF, basic-FGF and lithium were not growth promoting.     

The influence of three unchanging photoperiods on growth and parr-smolt transformation in Atlantic salmon, Salmo salar L.

Groups of pre-smolt Atlantic salmon were reared under three experimental photoperiods. Growth rate was significantly enhanced under 24 h of light: 0 h of darkness per diem (24 L: 0 D) compared with 16 L: 8 D and 8 L: 16 D from early January to early May. From the beginning of May until the termination of the experiment on 27 May, growth rate was highest under 8 L: 16 D.
All groups developed bimodal length-frequency distributions during the experiment. The proportion of the population in each of the two growth modes was significantly affected by photoperiod treatment.
The level of plasma cortisol increased significantly from February to May. There were no differences in levels of plasma cortisol among photoperiod treatments.
Judged by development in plasma cortisol, changes in condition factor and external appearance, the parr-smolt transformation was not completed under any of the experimental photoperiods.     

Effects of stimulation of hypothalamic “feeding areas” on endocrines and metabolism in normal and diabetic monkeys

Electrical stimulation of hypothalamic “feeding areas” (VMH & LHA) through stereotaxically implanted electrodes was carried out in normal and streptozotocinized diabetic conscious male rhesus monkeys. In normal monkeys, the VMH stimulation resulted in a significant decrease in serum insulin and blood glucose while opposite responses were observed following LHA stimulation. Serum growth hormone, FFA and plasma cortisol levels increased significantly on stimulation of LHA and VMH in normal animals. The pattern of blood glucose and serum growth hormone responses to stimulation of “feeding areas” was similar in normal and diabetic animals. The serum insulin, FFA and plasma cortisol were largely unaffected while growth hormone increased significantly by stimulation of these areas in diabetes. The present study indicates that the stimulation of “feeding areas” does not alter the diabetic syndrome significantly nor does diabetes prevent the changes in metabolism seen after stimulation of “feeding areas.”     

Growth, body composition and hepatic tyrosine aminotransferase activity in cortisol-fed channel catfish, Ictalurus punctatus Rafinesque

Metabolic consequences of chronic elevation of cortisol in the diet of yearling channel catfish, Ictalurus punctatus , were studied. Cortisol was incorporated into the diet in concentrations of 1, 10, 50 and 100 μg/g of food. This diet was offered at 3% of the body weight per day for 10 weeks. Fish were individually weighed and measured at 2-week intervals and feeding rates were adjusted. Body weight, liposomatic index and condition factor were significantly lower and food conversion was significantly higher in fish fed 50 or 100 μng cortisol/g of food when compared with controls. The hepatosomatic index of fish fed cortisol at the rate of 100 μg/g of food decreased significantly. Specific activity of hepatic tyrosine aminotransferase was significantly higher at the two highest cortisol doses. Long-term cortisol administration can reduce growth and condition factor by activating gluconeogenic mechanisms in which lipids and amino acids, rather than carbohydrates, are used for energy production. The metabolic effects of exogenous cortisol in this study offer an explanation for the decreased growth of fish under conditions that activate the secretion of endogenous cortisol.     

Plasma cortisol and growth hormone responses to intravenous characterization.

Plasma cortisol and growth hormone (HGH) responses to venous catheterization were studied in 29 volunteer subjects. Repeat characterizations were performed in 18 individuals. Mean plasma cortisol levels were significantly elevated during the first hour of the initial catheterization experience. Morning and afternoon levels of cortisol were not distinguishable during the first catheterization, but PM levels were significantly lower than AM levels during the second catheterization experience. Growth hormone responses were much more variable than cortisol and were distributed logarithmically. Growth hormone responses tended to parallel cortisol responses during the first catheterization experience. Individuals who listed more symptoms in response to venipuncture and catheterization after finishing their first catheterization had significantly higher cortisol and growth hormone levels during this experience. These data suggest a definite endocrine adaptation to catheterization by the second or third hour of the experience.     

A premature increase in circulating cortisol suppresses expression of 11beta hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid in the adrenal of the fetal sheep

We have investigated the effect of intrafetal cortisol administration, before the normal prepartum cortisol surge, on the expression of 11beta hydroxysteroid dehydrogenase (11betaHSD) type 2 mRNA in the fetal adrenal. We also determined whether increased fetal cortisol concentrations can stimulate growth of the fetal adrenal gland or increase expression of adrenal steroidogenic enzymes. Cortisol (hydrocortisone succinate: 2.0-3.0 mg in 4.4 ml/24 h) was infused into fetal sheep between 109 and 116 days of gestation (cortisol infused; n = 12), and saline was administered to control fetuses (saline infused; n = 13) at the same age. There was no effect of cortisol infusion on the fetal adrenal:body weight ratio (cortisol: 101.7 +/- 5.3 mg/kg; saline: 108.2 +/- 4.3 mg/kg). The ratio of adrenal 11betaHSD-2 mRNA to 18S rRNA expression was significantly lower, however, in the cortisol-infused group (0.75 +/- 0.02) compared with the group receiving saline (1.65 +/- 0.14). There was no significant effect of intrafetal cortisol on the relative abundance of adrenal CYP11A1, CYP17, CYP21A1, and 3betaHSD mRNA. A premature elevation in fetal cortisol therefore resulted in a suppression of adrenal 11betaHSD-2. Increased intra-adrenal exposure to cortisol at this stage of gestation is, however, not sufficient to promote adrenal growth or steroidogenic enzyme gene expression.     

Effect of sialoadenectomy on stomach lesions induced by indomethacin and ethanol in relation to gastric vascular permeability, the gastrin level and HCl secretion in rats.

Stomach lesions induced by indomethacin (20 mg.kg-1 i.p.) and ethanol (1 ml 95% intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCl secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v. administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EGF) (50 lg.kg-1). It was found that sialoadenectomy significantly (p < 0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p < 0.05). A significant increase in both basal and stimulated HCl secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol. The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCl secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.