Epimedium Flavonoids Counteract the Side Effects of Glucocorticoids on Hypothalamic-Pituitary-Adrenal Axis

Our previous studies demonstrated that the epimedium herb, when simultaneously used with GCs, counteracted suppressive effects of GCs on the HPA axis without adverse influence on the therapeutic action of GCs. Here, total flavones were extracted from the epimedium flavonoids (EFs) and then used to investigate whether EFs provide protective effects on the HPA axis. We found that GCs induced a significant decrease in body weight gain, adrenal gland weight gain, and plasma adrenocorticotropin (ACTH) and corticosterone levels. After treatment with EFs, body weight gain, adrenal gland weight gain, and plasma corticosterone level were significantly restored, whilst plasma ACTH level was partially elevated. EFs were also shown to promote cell proliferation in the outer layer of adrenal cortex and to enhance the migration of newly divided cells toward the inner layer. To elucidate the underlying mechanisms, the mRNA expression of insulin-like growth factor II (IGF-II) was measured, and EFs significantly upregulated IGF-II expression. Our results indicated that EFs counteract the suppression of the HPA axis induced by GCs. This may involve both the ACTH and IGF-II pathways and thereby promote regeneration of the adrenal cortex suggesting a potential clinical application of EFs against the suppressive effects of GCs on the HPA axis.

Effect of in Vivo Treatment with Delta9-THC on Mice Adrenal Gland

Introduction:The efficacy of antidepressants has been linked in part to their ability to reduce activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, the mechanism by which antidepressants regulate the HPA axis is largely unknown. Recent research has demonstrated that endocannabinoids can regulate the HPA axis and exhibit antidepressant potential.Aim:The purpose of this study was therefore to evaluate the effect of chronic administration of delta-9-tetrahydrocannabinol (delta9-THC) on the adrenal gland of mice.Methods:Delta9-THC (10 mg/kg, 1 THC:1 chremophor:18 saline) or vehicle (CT, 1 chremophor:18 saline) was administered i.p. for 10 days to C57Bl6 mice aged 15 weeks. At the end of the study rats were placed in metabolic cages. Noradrenaline (NA) and adrenaline (AD) levels in samples and tissues were evaluated by HPLC-ED. Statistical analysis was done by ANOVA followed by Student's t test. Results are presented as mean±SEM.Results:Treatment with delta9-THC did not produce changes in mice weight (CT: 25±1; delta9-THC: 24±1 g, n=5-6) but produced a significant reduction in adrenal gland weight (CT: 1.4±0.2; delta9-THC: 0.6±0.1* mg, n=5-6, *P˂0.01). However, treatment with delta9-THC did not produce significant changes in NA and AD adrenal content (NA: 7.5±2.1, 5.3±0.6; AD: 14.1±1.1, 11.1±2.1 nmol, CT and delta9-THC respectively, n=5-6) or in NA and AD urine levels (NA: 0.88±0.06, 1.18±0.17; AD: 0.64±0.07, 0.81±0.09 nmol/24h, CT and delta9-THC respectively, n=5-6).Conclusion:Chronic treatment with delta9-THC reduces adrenal gland weight in mice. These results suggest that endocannabinoids may act directly at the adrenal gland to regulate the HPA axis.

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams ( n = 6–8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors.

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.

Local variation in endoparasite intensities of bank voles (Clethrionomys glareolus) from ecologically similar sites: morphometric and endocrine correlates

Much interest has centred recently on the role of adaptive trade-offs between the immune system and other components of life history in determining resistance and parasite intensities among hosts. Steroid hormones, particularly glucocorticoids and sex steroids, provide a plausible mechanism for mediating such trade-offs. A basic assumption behind the hypothesis, however, is that steroid activity will generally correlate with reduced resistance and thus greater parasite intensities. Here, we present some findings from a field study of bank voles (Clethrionomys glareolus) in which we have looked at associations between parasite intensities, anatomical and morphometric measures relating to endocrine function and life history variation in three local populations inhabiting similar but mutually isolated woodland habitats. In general, sites with greater parasite intensities were those in which male C. glareolus had significantly larger adrenal glands, testes and seminal vesicles for their age and body size. Females also showed a site difference in adrenal gland weight. Some aspects of site-related parasite intensity were associated with asymmetry in adrenal gland weight and hind foot length, which may have reflected developmental effects on glucocorticoid activity.

Effect of on-farm and pre-slaughter handling of pigs on meat quality

Thirty-six crossbred (Large White × Landrace) boars were used to investigate the effect of positive and negative handling of pigs on-farm over a period of 5 weeks, and the effect of minimal and negative handling just prior to slaughter at the abattoir on the level of stress and meat quality of the carcass. There was no significant difference in adrenal gland weight and plasma cortisol concentration measured at slaughter between pigs negatively and positively handled on-farm. Pigs negatively handled on-farm had lower muscle glycogen 5 min and 40 min post slaughter in the Longissimus thoracis (LT) but muscle paleness and percentage drip loss of the LT were similar compared with pigs positively handled on-farm. Pigs negatively handled at the abattoir had lower muscle glycogen 5 min post slaughter in the LT; however, muscle paleness, percentage drip loss, ultimate pH, and incidence of pale, soft, exudative meat were similar compared with pigs that were minimally handled at the abattoir. This study has shown how the interaction between pigs and humans on-farm can influence the pig’s ‘stress’ response to pre-slaughter handling and, potentially, meat quality.