Adrenalectomized rats

Studies have shown that aldosterone (19) (112,113) from adrenal extracts was intensely active in the survival and sodium retention assays in the adrenalectomized rat. 

Grillo, C., Piroli, G., Lima, A., McEwen, B. S. and DeNicola, A. F. Aldosterone up-regulates mRNA for the alpha3 and betal isoforms of (Na,K)-ATPase in several brain regions from adrenalectomized rats. Brain Res. 767 120-127,1997. 

H0. Hess, R., and Gross, F., Glucose-0-phosphate dehydrogenase and renin in kidneys of hypertensive or adrenalectomized rats. Am. J. Physiol. 197, 809-872 (1959). 

Brown LD, Yarbrough JD. 1988. Mirex uptake and tissue disposition in intact and adrenalectomized rats. Toxicol Appl Pharmacol 92(3) 343-350. 

Table 13. Glucorticoid and antiinflammatory activity of l-(chloromethyl)silatrane on subcutaneous administration at 100 mg/kg per day to adrenalectomized rats (3 groups containing 20 animals each)... 

In 1957, Celia and Kagawa [5] reported about the preparation of two steroidal 17-spirolactones, which were capable of blocking the urinary sodium/potassium action of aldosterone and desoxycorticosterone-acetate in adrenalectomized rats. These compounds were closely related in structure to aldosterone and were assigned the code names SC 5233 and SC 8109, respectively. Structures of these three compounds are shown in Figure 1. 

Fig. 2. The action of hormones on growth and milk secretion in the mammary glands of hypophysec-tomized-ovariectomized-adrenalectomized rats. From Ref. 14.

Adrenalectomized rats treated with DOCA or aldosterone can be utilized to test aldosterone antagonists. Spironolactone has no effect in the absence of a min-eralocorticoid, but reverses in a dose-related manner the effect of DOCA on the Na+/K+ ratio in the urine (Kagawa et al. 1957 Bicking et al. 1965). 

Figure 3. Changes in the molecular localization of Mn in rat liver and pancreas following injection with 10 mg Mn/kg BW. Control rats ( -— ), adrenalectomized rats (O---O). Chromatog-...

Fischer AK, von Rosenstiel P, Fnchs E, Gonla D, Almeida OF, Czeh B (2002) The prototypic mineralcorticoid receptor agonist aldosterone inUnences neurogenesis in the dentate gyrus of the adrenalectomized rat. Brain Res 947 290-293. 

Aberrant levels of PGDH activity can be modified. Thus, hydrocortisone reverses excessive renal PGDH in adrenalectomized rats, while 17/3-oestradiol reverses increased PGDH activity in ovariectomized rats. Since both steroids are without effect In vitro, the mechanism remains uncertain. Purified swine kidney PGDH has been inhibited by relatively high doses of thyroid hormones... 

Nichols, N. R., Laping, N. J., Day, J. R., and Finch, C. E., Increases in transforming growth factor-(3 mRNA in hippocampus during response to entorhinal cortex lesions in intact and adrenalectomized rats, J. Neurosci. Res., 28, 134, 1991. 

Pyrazines. N-Amidino-3-amino-6-chloropyrazinecarboxamide (Xl) previously was shown to reverse the electroi e excretion effects of deoxycorticosterone acetate in the adrenalectomized rat and was shown to be a potassium-sparing natriuretic agent in the intact rat and dog. ... 

N-amidino-3,5-dlamino-6-chloropyrazinecarboxamlde (Xlla) is most active, producing a reversal of the DOGA effect in adrenalectomized rats at 2.5 ig./rat. XI produces an equivalent effect at 36 pg./rat. 

FIGURE 19.4 PK/PD modeling results using the fifth-generation model. Symbols and differential equations for the model are defined in Eqs. (19.1)-(19.11). Adrenalectomized rats received 50mg/kg intravenous injection of MPL at Oh. (A) Plasma MPL concentration (B) simulated drug-receptor complex in hepatocyte nucleus (DR(N)) (C) GR mRNA level in hver (D) free GR density in liver (E) TAT mRNA level in liver and (F) TAT activity in liver versus time. Solid circles are the observed data and bars are the standard deviations. Lines are model predictions. (Adapted from Refs. 6 and 7.)... 

Kato, K., Selective repression of benzoate or tryptophan mediated induction of liver tyrosine aminotransferase by phentolamine in adrenalectomized rats, FEBS Lett., 8, 316, 1970. 

Majumdar, A. P. and Jorgensen, A. J., Response of well-fed adrenalectomized rats to tryptophan force-feeding on hepatic protein and RNA synthesis, Biochem. Med., 16[3], 266, 1976. 

Jorgensen and Majumdar125 reported that a single tube-feeding of L-tryp-tophan to well-fed adrenalectomized rats stimulated in vivo incorporation of [3H] leucine into brain proteins as well as liver proteins. Also, Nakhla and Majumdar126 reported that tube-feeding tryptophan to well-fed adrenalectomized rats induced an increase in the activity of cerebral acetylcholinesterase, which could be prevented when the animals were pretreated with actinomycin D. Whether or not the enhanced protein synthesis in the brain following tryptophan administration may be related to a rise in brain serotonin level caused by increased plasma tryptophan concentration is not known. 

Jorgensen and Majumdar125 reported that a single tube-feeding of L-tryp-tophan to well-fed adrenalectomized rats stimulated in vivo incorporation of [3H]leucine into kidney proteins. 

Nakhla, A. M. and Majumdar, A. P., Tryptophan force-feeding Changes in the activities of acetylcholinesterase in various tissues of well-fed normal and adrenalectomized rats, Biochem. Biophys. Res. Commun., 79, 96, 1977. 

A slow moving aa-globulin— variously designated aa-acute phase (AP) or a-2-glycoprotein (GP)— which is not normally detectable in the plasma of patients and experimental animals, appears in acute inflammatory states and after injury in general. It appears in the plasma 12-18 hours after the injury and remains detectable for 7-10 days or longer. Adrenalectomy prevents its appearance after injury. It can be restored in the adrenalectomized rat by corticosterone or cortisol. [For review see (BIO, 02, W8, W9).]... 

There is a linearity of response to graded cortisol treatment in traumatized adrenalectomized animals (Bll). The adrenal cortical control of the appearance of slow a2-globulin is incomplete in the 2-day postpartum maternal rat, because the globulin can be demonstrated in most adrenalectomized animals in this condition. Adrenal cortical control over the appearance of the globulin is not simply in the postpartum maternal animal, because the percentage of adrenalectomized rats with demonstrable slow [Pg.17]

The role of the adrenal gland in various responses to various stresses has been widely studied. John (Jl) found that sound stress for a period of 1.5 hours produced marked lymphocytopenia in normal but not adre-nalectomized rats. Estimating the normal daily in vivo production of corticoid to be equivalent to 0.8 j ,g of cortisone acetate per kilogram body weight injected subcutaneously as an aqueous suspension, Johns noted that injection of 4.0 mg of cortisone acetate per 100 g body weight into adrenalectomized rats resulted in lymphocytopenia. Injection of doses of cortisone acetate more equivalent to the normal daily secretion of corticoid in intact animals did not produce lymphocytopenia in adrenalectomized rats, but did restore the lymphocytopenic response to sound stress. 

R2. Redgate, E. S., Spinal cord and ACTH release in adrenalectomized rats following electrical stimulation. Endinocrinology 70, 263-266 (1962). 

W8. Weimer, H. E., and Coggshall, V., Divergent responses of serum glycoprotein fractions to tissue injury in adrenalectomized rats. Can. J. Physiol. Pharmacol. 46, 767-776 (1967). 

Our animal screening method essentially consists in the oral administration of the test drug to glucose-primed intact and adrenalectomized rats and the estimation of potency from dose-response curves compared with tolbutamide as the standard (9). 

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