Septum and adrenocortical function

Dorsal septum is an intermediary centre in between the hippocampus and hypothalamus and it has got inhibitory influence over the hypothalamo-pituitary-adrenal axis. Stimulation of the dorsal septum manifested with fall in adrenocortical output whereas its lesion has opposite response. Ventral septum is a facilitatory area regarding activation of the hypothalamo-pituitary-adrenal axis. It is a balancing centre lying in between the higher central nervous system structures and the hypothalamus. Stimulation and lesion of the ventral septum led to rise and fall in adrenal venous 17-OHCS output respectively. Adrenocortical response to stress of burn was not blocked or inhibited following lesion of the dorsal as well as ventall septum.     

Effect of difluprednate on adrenocortical and gonadal function

The effects of difluprednate on the deposition of liver glycogen, the inhibition of adrenocortical function, the estrogenic, progestational and androgenic activities, and the excretion of electrolytes were investigated by comparing them with those of fluocinonide. The following results were obtained: 1) the deposition of liver glycogen was remarkably increased by subcutaneous administration of these two glucocorticoids, and in the dose of 0.1 mg/kg, the effect of difluprednate (35.1-fold the control value) was larger than that of fluocinonide (19.4-fold the control value) in mice. 2) the administration of difluprednate and fluocinonide greatly induced the decrease in the corticosterone concentration in the rat serum and adrenal gland (0.1 and 1 mg/kg, s.c.). 3) the estrogenic, progestational and androgenic activities were not recognized by administration of difluprednate in rats. 4) the two glucocorticoids induced an increase in the electrolytes excretion (especially K+) and the urine volume. 5) by the repeated injection of difluprednate (1.0 mg/kg) and fluocinonide (0.1 mg/kg), decrease of the body weight was observed in all of the experimental animals. In these experiments, it was recognized that the glucocortical action of difluprednate was similar or more potent in comparison with the action of fluocinonide and that the systemic effects of fluocinonide such as body weight loss was larger than that of difluprednate.     

Adult behavior and adrenocortical function following neonatal morphine treatment in rats

Adult behavioral and endocrine effects of neonatal administration of morphine (M) were studied in female rats injected s.c. with M on either days 3–12 (M₁) or days 12–21 (M₂). The dose given twice daily was increased to 8 mg/kg in group M₁ and to 16 mg/kg in group M₂. Compared to saline-treated controls, growth rates were temporarily suppressed (P<0.05) and body weights were reduced (P<0.05) util day 20 in M₁ and until day 64 in M₂ rats. The open-field test performed on days 29–31 failed to differentiate between neonatal treatment groups. On days 90–95 M₁ but not M₂ animals showed impaired learning of a conditioned emotional responses (CER). On day 40 all groups showed similar increased levels of plasma corticosterone 30 min following injection of naloxone (5 mg/kg). Compared to controls on day 156, both M₁ and M₂ rats showed diminished (P<0.05) analgesic responses (hot-plate test) to M (10 mg/kg). In response to M challenge (40 mg/kg) on day 170, all groups showed comparable acute increases in plasma corticosterone levels. These findings provide further evidence that early exposure to M results in growth retardation and protracted tolerance and that, depending on dose and time of exposure, neonatal M may result in impaired learning of CER in adulthood. These effects suggest that early morphine can produce long-lasting alterations of learned behavior without lasting impairment of pituitary-adrenal function.     

Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs

The influences of in vivo treatment with two pure PCB congeners, 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP) and 3,3',4,4'-tetrachlorobiphenyl (TCBP), on the lethal cytotoxicity of bromobenzene and acetaminophen were examined in short-term primary cultures of isolated rat hepatocytes. Lethal injury was measured by release of lactate dehydrogenase (LDH) into culture medium after 20 hr exposure to the hepatotoxins. The HCBP, a PB-type inducer of cytochrome P-450, resembled phenobarbitone (PB) in its ability to increase susceptibility of hepatocytes to bromobenzene (0.5 to 1.6 mM) and acetaminophen (1 to 16 mM). This induced sensitivity was consistently inhibited by SKF-525-A (10 microM) but not alpha-naphthoflavone (ANF, 10 microM) in culture. The 3,3',4,4'-TCPB, a 3-MC-type inducer of cytochrome P-450, resembled 3-methylcholanthrene (3-MC) in its inability to induce susceptibility to bromobenzene. TCBP and 3-MC each increased (20- to 30-fold) cytotoxicity of acetaminophen by a mechanism substantially inhibitable by ANF but not SKF-525-A. These results demonstrate that categorizing pure PCB isomers and congeners into groups according to their different induction capabilities is predictive for their ability to modulate acute hepatocellular necrosis by bromobenzene and acetaminophen.     

Inhaled corticosteroids in childhood asthma: long-term effects on growth and adrenocortical function

Inhaled corticosteroids (ICS) are the most potent of all the available inhaled treatments, and are effective medications for long-term control of asthma. However, their use in children is limited by the risk of systemic adverse effects. Although results reported in the literature on the adverse effects of ICS are conflicting and often restricted to a small number of cases with a limited follow-up, most of them show an early decrease in growth velocity without significant influence on final adult height. Partial adrenal suppression has also been demonstrated in children treated with ICS for more than 2 months. Only children with mild persistent, moderate, or severe asthma not controlled by non-corticosteroid drugs should be treated with ICS for long periods. The dose of ICS must be individually adjusted to minimize the possible adverse effects on growth, and all children with asthma receiving long-term treatment with ICS must be regularly evaluated for growth impairment, which may necessitate dose reduction or drug replacement.     

Hypothalamo-pituitary adrenocortical function in the rat after treatment with betamethasone.

1 Hypothalamo-pituitary-adrenocortical (HPA) activity was suppressed in rats treated with betamethasone. 2 Recovery of normal HPA function occurred after corticosteroid withdrawl. 3 Although corticotrophin release was rapidly restored to its basal rate there was a delay in the return of the normal adrenocorticotrophic response to stress and normal adrenocortical function was evident only after the plasma adrenocorticotrophic hormone had reached 'supra-normal' levels. 4 The physiological significance and possible clinical relevance of the results are discussed.     

Suppression of adrenocortical function in female mice by lindane (gamma-HCH).

Lindane (gamma-HCH) given to adult female mice orally at various doses and over varying periods adversely affected adrenocortical function. Adrenal weights decreased and both fasciculata and reticularis zones markedly regressed. Histopathological lesions were also noted and plasma and glandular glucocorticoid contents were significantly reduced. Simultaneously an increase in cholesterol and a decrease in ascorbic acid content of the adrenal glands were noticed. The adrenotoxic effect of this chlorinated insecticide possibly results from depressed corticoid production in situ and/or suppressed activity of enzyme(s) that catalyze the peripheral transformation of steroids.     

Effects of exposure to nanoparticle-rich diesel exhaust on adrenocortical function in adult male mice

To investigate the effects of nanoparticle-rich diesel exhaust (NR-DE) on adrenocortical function, seven-week-old male mice were divided into four groups and exposed to either whole NR-DE at low (41.73 μg/m³, 8.21 × 10⁵ particles/cm³), high (152.01 μg/m³, 1.80 × 10⁶ particles/cm³) concentrations, filtered diesel exhaust (F-DE) or clean air for 8 weeks (5 h/day, 5 days/week). After 8 weeks of exposure, the animals were euthanized under pentobarbital anesthesia and the blood samples were collected to detect serum progesterone and corticosterone. In addition, adrenal glands were excised, and adrenal cells were cultured in the absence or presence of rat adrenocorticotropic hormone (ACTH) (10⁻¹⁵ to 10⁻¹⁰ M) for 4 h. There were no significant differences in the body weight, absolute and relative adrenal gland weight among the groups. Serum concentration of corticosterone and progesterone was not changed significantly. Administration of ACTH resulted in a dose-dependent increase in corticosterone and progesterone release in mice-exposed to low-concentration NR-DE and clean air. Moreover, corticosterone and progesterone concentrations in adrenal cells increased significantly in mice-exposed to low-concentration NR-DE basal and administrated with ACTH (10⁻¹⁵ to 10⁻¹¹ M for corticosterone; 10⁻¹⁴ to 10⁻¹¹ M for progesterone) compared with the control mice. In contrast, the concentration of corticosterone and progesterone decreased significantly in mice-exposed to high-concentration NR-DE or F-DE basal and administrated with ACTH (10⁻¹² to 10⁻¹⁰ M for corticosterone; 10⁻¹⁵ to 10⁻¹⁰ M for progesterone) compared with the control mice. These results suggest that exposure to NR-DE or F-DE may disrupt adrenocortical function in adult male mice.     

Brain monoamines and adrenocortical activation

1. The effect of a pharmacologically induced increase or depletion of brain monoamines (5-hydroxytryptamine, noradrenaline, dopamine) was investigated with respect to adrenocortical function.2. No strict correlation was found between the depletion of brain amine stores induced by prenylamine or p-chlorophenylalanine and adrenocortical activation, even at times in which the peak effect of brain amine depletion occurs.3. Restraint stress causes a manifest increase in brain 5-hydroxytryptamine while decreasing the cerebral noradrenaline and dopamine content. This stress strongly stimulates corticosterone secretion by the adrenals.4. A monoamine oxidase inhibitor, nialamide, at a dose which causes an evident increase in brain amine concentrations, does not modify plasma corticosterone. At the same dose it was, furthermore, unable to prevent the adrenocortical stimulation induced by restraint stress.5. Brain amine content does not seem to play an important part in the control of corticotrophin releasing factor in corticotrophin secretion by the pituitary gland. The relationship between hypothalamic monoamines and other neurohumours is discussed.