Effect of adrenalectomy on rat peritoneal macrophage response

Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. In contrast to other hormonal systems no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Glucocorticoids are known to interfere with the ability of the macrophage not only to induce and amplify an immune response but also to inhibit macrophage inflammatory effector functions. Although the actual immunocompetence of animals undergoing endocrine gland ectomy has never been directly studied, there is no doubt that adrenal hormones are deeply involved in the development and maintenance of the immunitory functions and this may in turn influence the inflammatory reaction. To study the effect of endogenous glucocorticoids on the functions of rat peritoneal macrophages and induction of humoral immune response we observed some of the rat peritoneal macrophage effector functions, provided that endogenous glucocorticoids are depicted by adrenalectomy. The mean phagocytic index (PI) of control macrophage (Mphi) is increased from 23,825 +/- 427 to 31,895 +/- 83 after adrenalectomy (P < or = 0.001). Intracellular killing capacity in control cell is 82% which is found to be 73% in case of adrenalectomised cell (p < 0.05). The amount of nitric oxide released from control Mphi 20.25 +/- 1 microM following adrenalectomy shows the amount of nitric oxide release was 18.25 microM (p < or = 0.01 ). The percentage of DNA fragmentation in control Mphi was 68.82 +/- 4 which was reduced to 56.76 +/- 1 after adrenalectomy (p < or = 0.01). In sheep red blood cell (SRBC) immunised and adrenalectomised animal, agglutination titre was obtained at lowest antibody concentration (1 : 128) whereas serum from SRBC immunised normal rats showed early agglutination (1: 32). Endogenous glucocorticoid depleted rats show enhanced phagocytic capacity, antibody raising capacity as well as on the other hand adrenal hormone insufficiency reduces the intracellular killing capacity, nitric oxide (NO) release, improper cell maturation and heightens the probability of infection. These observations demonstrate a counter-regulatory system via glucocorticoid that functions to control inflammatory and immune responses.     

Effect of adrenalectomy on the diurnal variation of hepatic cholesterogenesis in the rat

The diurnal variation in cholesterol synthesis exhibited by rat liver has been examined in fed, fasted, and adrenalectomized animals. Fasting for 3 days caused a lowering of the rate of synthesis but did not abolish the diurnal rhythm. Adrenalectomy abolished the diurnal variation, and caused synthesis to remain at a uniformly high level. We suggest that corticosterone may play an essential role in the daily rhythm of cholesterogenesis.     

Effect of adrenalectomy on Ca2+ signaling in rat hepatocytes

To pursue our studies of the effects of adrenalectomy on the adrenergic regulation of phosphorylase a, cAMP, cell calcium, and Ca2+ signaling in rat hepatocytes (Studer, R.K., and Borle, A.B. (1984) Biochim. Biophys. Acta 804, 377-385; Freudenrich, C.C., and Borle, A.B. (1988) J. Biol. Chem. 263, 8604-8610), we have further examined the alpha 1-adrenergic pathway in adrenalectomized and sham-operated male rats. We measured the number and affinity of alpha 1-adrenergic receptors, the cytosolic free Ca2+ concentration [(Ca2+]i) of hepatocytes with aequorin, inositol triphosphate (IP3) accumulation, and Ca2+ influx and efflux across the plasma membrane. We also compared the effects of vasopressin with those obtained with epinephrine. We found that the number of alpha 1-adrenergic receptors was slightly depressed (-23%), but that their affinity was unchanged. However, IP3 accumulation evoked by epinephrine was decreased 50%. This is probably the main cause for the depressed peak rise in [Ca2+]i we previously observed and reported. We also found that the basal resting Ca2+ influx was increased after adrenalectomy. Experiments with the beta-blocker propranolol, which abolished the epinephrine-evoked increase in Ca2+ influx, suggest that this effect may be mediated by cAMP, at least in adrenalectomized animals. The effects of vasopressin on IP3 [Ca2+]i and Ca2+ influx and efflux were also significantly decreased after adrenalectomy, indicating that alpha 1-adrenergic-mediated and other IP3-dependent Ca2+ signaling pathways are depressed after adrenalectomy.     

Effect of adrenalectomy on distal tubule water permeability of the Brattleboro rat

The mechanism of impaired water excretion in adrenalectomized mammals is unclear. Previous workers have suggested that one cause might be increased water permeability of the distal nephron, allowing back diffusion of water from tubular fluid diluted by the ascending limb. Evidence to support this mechanism in previous studies has been confounded by simultaneous changes in steroid and antidiuretic hormone levels. We compared osmotic and diffusional water permeability of the surface late distal tubule in vivo in intact and adrenalectomized Brattleboro rats, which are free of antidiuretic hormone. The adrenalectomized rats were demonstrated to have impaired diluting capacity in clearance studies. Adrenalectomized rats had a sixfold increase in osmotic permeability and a 1.5-fold increase in diffusional permeability over intact controls. Adrenal steroids have a specific action on water permeability of the distal nephron, independent of antidiuretic hormone.     

Effect of adrenalectomy and aldosterone on the modulation of mineralocorticoid receptors in rat kidney

Adrenalectomized rat kidney is commonly used for the study of mineralocorticoid mechanism of action in mammals. In this model, aldosterone is known to bind to two classes of binding sites: type I (mineralocorticoid) and type II (glucocorticoid). The study of the aldosterone binding in normal rat kidney requires the elimination of endogenous hormones bound to each type of receptor. Thus, a suitable technique was developed using in situ perfusion of the kidneys. The efficacy of this method was of about 85 to 90% at the level of both cytoplasm and nucleus. Aldosterone binding capacity was checked in normal rat kidney after in situ perfusion and was found to be 300 to 500% lower than in adrenalectomized rat kidney, both in cytoplasm and nuclei. Computer analysis of aldosterone binding parameters in the cytoplasm (30,000 X g supernatant) of rat kidney suggested that adrenalectomy might induce an important rise in the number of mineralocorticoid receptors (congruent to 260%). An increase in the number of glucocorticoid receptors was also observed but appeared to be lower. Aldosterone, when perfused during 24 h in adrenalectomized rats, lowered the number of type I sites to the same level as observed in normal rat kidney. This effect was fully reversible after interruption of aldosterone perfusion. These results suggested an aldosterone-induced down regulation of mineralocorticoid receptors.     

Effect of ACTH, dexamethasone, and adrenalectomy on the secretion of testosterone in the rat

The effect of ACTH (100 micrograms/animal/day, i.p.), dexamethasone (75 micrograms/animal/day, s.c.), both for three consecutive days, and adrenalectomy, with or without dexamethasone, maintained according to the group, one, two or three days, on the plasmatic testosterone and corticosterone levels, has been studied in adult male Wistar rats. ACTH and adrenalectomy produced a high decrease in testosterone levels (p less than 0.001 for the three days studied). Dexamethasone produced lower testosterone levels in the first day followed by partial recuperation between the second and the third days of its administration. Dexamethasone produced the effects mentioned for intact animals. The changes in corticosterone levels were according to an adequate response of the hypothalamus-pituitary-adrenal system under these experimental circumstances. ACTH exerts an inhibitory effect on testosterone secretion in the rat, so that such an effect from the data obtained after adrenalectomy and simultaneous dexamethasone injections, does not seems to be mediated either by the presence of adrenals or high corticosterone levels.