Adrenalectomy eliminates both fiber-type differences and starvation effects on denervated muscle

This report describes changes in muscle mass of innervated and denervated pairs of muscles taken from intact and adrenalectomized 250-g male Sprague-Dawley rats provided with different diets. Diets ranged from a nutritionally complete liquid diet to starvation (water only). In the intact animals, muscles with a more tonic character (soleus) are less sensitive to starvation than are muscles with a more phasic character (extensor digitorum longus), whereas the opposite is true of denervation. In the intact animals, starvation greatly increased the amount of atrophy following denervation. In the adrenalectomized animals, starvation had no effect on the amounts of atrophy following denervation. Furthermore, adrenalectomy virtually eliminated the fiber-type differences in the amount of atrophy following denervation. In addition, a comparison between denervated muscles from intact animals and adrenalectomized animals subjected to starvation demonstrates that all denervated muscles from the adrenalectomized animals atrophy less. Finally, it was observed that although an adrenalectomized animal can tolerate 6 days of starvation, an adrenalectomized-castrated animal cannot tolerate even short periods of starvation. The difference appears to be due to low amounts of corticosterone of testicular origin.

PLASMA CORTICOSTERONE LEVELS DURING PREGNANCY IN THE MOUSE: THE RELATIVE CONTRIBUTIONS OF THE ADRENAL GLANDS AND FOETO-PLACENTAL UNITS

SUMMARY Plasma corticosterone levels were measured throughout pregnancy and on the first day post partum in the mouse. During the first half of pregnancy plasma corticosterone levels rose from the non-pregnant value of 2·3 μg/100ml to 15·2 μg/100 ml on day 10. During the second half of pregnancy there was a sharp rise, levels reaching a peak of 138·3 μg/100ml on day 16. Following parturition there was a rapid fall to 18·3 μg/100 ml on the morning of the first day post partum. Adrenalectomy on day 15 resulted in an 80% fall in plasma corticosterone levels indicating that most of the steroid was of adrenal origin. The remaining portion of the corticosterone was found to be of foeto-placental origin, and in the chronically adrenalectomized animal this source was capable of maintaining high blood levels of corticosterone (67 μg/100 ml). The foeto-placental unit also provides the main secretory stimulus to the adrenal gland, but the mechanism by which it does this is not understood.

Corticosteroids for reversal of hemorrhagic shock in rats

Corticosteroids administered in amounts more than 100 times those required to sustain a fully adrenalectomized animal were highly effective in increasing survival following hemorrhagic shock. In rats with intact adrenal glands, hemorrhagic shock was produced by maintaining arterial blood pressure at 35 mm Hg for 240 min. Glucocorticoids and aldosterone were administered only after blood was reinfused. The therapeutic benefit is due to a pharmacological action of the adrenocortical hormone. Aldosterone had a lesser and relatively narrow dosage range of effectiveness.

Hormonal factors in the rat's tolerance to altitude

The survival period of adrenalectomized rats, which are less tolerant than normal rats to reduced barometric pressure (equiv. to altitude of 27,800 ft), can be extended when the animals are pretreated with adequate amounts of cortisol. Pretreatment of adrenalectomized animals with somatotropin (0.5 mg/100 g body wt.) did not have any significant effect on tolerance to simulated altitude, but when somatotropin was administered simultaneously with a subeffective dose of cortisol, tolerance to altitude was significantly increased. Thyroidectomy did not have a beneficial effect on survival of adrenalectomized animals, but pretreatment of adrenalectomized-thyroidectomized rats with 3 mg cortisol, which is inadequate to protect the adrenalectomized animal against exposure to simulated altitude, significantly increased survival rate. A possible mechanism whereby lesser amounts of cortisol are effective in prolonging survival of thyroidectomized-adrenalectomized rats exposed to low barometric pressure may be a decrease in catabolism of the steroid in hypothyroid animals.

THE IN VITRO UTILIZATION AND PRODUCTION OF NON-ESTERIFIED FATTY ACIDS BY ADRENALECTOMIZED RATS

The in vitro utilization of non-esterified fatty acids by various tissues and the in vitro production of non-esterified fatty acids by adipose tissue have been compared in normal and adrenalectomized rats. It was found that the production of NEFA by adipose tissue was similar in both groups of animals but that the in vitro utilization of NEFA and production of carbon dioxide by heart, diaphragm, kidney, and liver tissue was greater in the adrenalectomized animal. These findings together with the depletion of fat content of the depots are interpreted as indicating that in the adrenalectomized state there is increased peripheral utilization of fatty acids.

Altered physiological status and [Na] and [K] in intracellular particulates of rat kidney

The effects of adrenalectomy, ethanol and aldosterone have been studied on the [Na] and [K] in intracellular particulates prepared from the kidneys of rats on varied sodium intake. The microsome has the highest intracellular concentration of sodium and is the site of marked, independent changes in response to ethanol, aldosterone and high sodium intake. These changes are limited primarily to sodium and potassium ions not readily eluted from this fraction in aqueous solution. Adrenalectomy decreases the [Na] and [K] in all cellular fractions. This change is inhibited by saline supplementation after adrenalectomy. Aldosterone selectively increases the [Na] of the microsome fraction, an effect contrary to that of ethanol. Increased sodium intake in the intact animal blocks the response to ethanol and, in the adrenalectomized animal, the response to aldosterone. Saline supplementation causes a selective increase in microsomal [K], an effect unrelated to adrenalectomy, ethanol or aldosterone. The conclusion suggested is that the microsome fraction is related to renal cellular electrolyte metabolism although the nature of this relationship is obscure.

SOME OBSERVATIONS ON THE EXCRETION OF 17-KETOSTEROIDS AND 17-KETOGENIC STEROIDS BY GUINEA-PIGS

SUMMARY 1. 17-Ketosteroids (KS) and 17-ketogenic steroids (KG) may be determined in guinea-pig urine by the method of Norymberski, Stubbs & West [1953]. Studies on the fractionation of urinary steroids showed the method was applicable to the urine of pregnant guinea-pigs. 2. So little material in the faeces of guinea-pigs behaved as KS that excretion by this route may be ignored. 3. Daily vaginal lavages shortened the oestrous cycle in the guinea-pig and abolished the peak of KS excretion seen at oestrus in normal cycles. No consistent trend in the excretion of KG was seen during normal oestrous cycles. No cyclical change in KS excretion was seen after ovariectomy. 4. During pregnancy in the guinea-pig, there was a rise in the excretion of KG and KS. The increase was not abolished by ovariectomy. The rise did not occur in one adrenalectomized animal which went to term, though it continued to excrete significant amounts of KS. The contribution of the foetal adrenals to the excretion of steroids by the pregnant mother was probably small. 5. Non-specific adrenal stimulation caused a rise in the urinary excretion of KS and KG. 6. Fractionation of the KS released from the urine of an intact non-pregnant guinea-pig by a mild hydrolytic procedure gave five major compounds, one in the 11-deoxy and four in the 11-oxy fraction. All five compounds were excreted in increased amounts by a pregnant intact and by a pregnant adrenalectomized guinea-pig.

Effects of Aldosterone on Blood Pressure and Electrolyte Distribution in the Rat

Aldosterone racemate, 20–40 µg, induced a small rise in blood pressure in the intact or nephrectomized rat following subcutaneous or intravenous but not intraperitoneal injection. It was effective in restoring the depressed pressure of the adrenalectomized animal towards normal within 60 minutes of intravenous administration. Extracellular fluid volume (inulin space) and extracellular Na were increased in the nephrectomized rat, but not in the nephrectomized-adrenalectomized animal during the restoration of blood pressure. Aldosterone racemate, 20 µg, also caused a characteristic increase in pressor sensitivity to Pitressin within 30 minutes of subcutaneous administration. Based on these findings and our previous studies, argument is presented to link the neurohypophysis and mineralocortex, both acting by different means in the same direction, with the control of sodium distribution between cells and environment. Vascular smooth muscle tonus is considered to be a function of the continuously regulated sodium gradient and thus of the sodium transfer systems. Plasma sodium changes in diverse states with altered blood pressure are considered to be evidence of attempts at compensation for an altered sodium gradient rather than as causal in themselves.

Respiratory Studies on the Utilization of Carbohydrate After Adrenalectomy

Respiratory quotients and C14O2 production from 2-C14 pyruvate were studied in normal and adrenalectomized rats following subcutaneous epinephrine as a carbohydrate mobilizing agent. The adrenalectomized rats responded with a rise in R.Q. that was greater and more prolonged than that of the controls. They also expired more C14O2 than did the normal animals during the 4-hour period of study. These data are consistent with an increased rate of oxidation of carbohydrate by the adrenalectomized animal rather than increased lipogenesis.