Dwight J. Ingle

Increase in Glyceride Content of Brown Fat by Treatment with Adrenocorticotropin.

Summary Treatment of intact or castrated rats with ACTH caused an increase in the glyceride content of brown adipose tissue. Treatment of hypophysectomized rats with 3 times the dose used above failed to maintain the fat content of the interscapular gland at a normal level.

A Simple Means of Producing Obesity in the Rat

Summary Obesity can be produced in the albino rat by restriction of activity and by the ad libitum eating of a diet which is appetizhg to the anilmal.

Effect of Treatment with AGTH or Cortisone on Anatomy of the Brain.

Summary Administration of ACTH caused chromatolysis in the cells of the paraventricular hypothalamic nucleus. Cortisone affected this nucleus but induced more widespread chromatolysis and vacuolation of thalamic and hypothalamic nerve cells.

Atrophy of the Thymus in Normal and Hypophysectomized Rats Following Administration of Cortin

Moon 1 noted atrophy of the thymus in rats following administration of the adrenotropic principle of the anterior lobe of the pituitary glands. His observations have been confirmed by Lyons and Simpson of the same laboratory. 2 This investigation deals with the effect on the thymus of administering massive amounts of cortin to normal rats and to rats which had been hypophysectomized. Forty male rats, each having an initial body weight of 180 g, were used. Ten normal animals were untreated and 10 normal animals each received 10 cc of cortin daily in their drinking water (each cubic centimeter of cortin represented 75 g of adrenal glands). Twenty hypophysectomized rats each received an amount of adrenotropic hormone daily which previous assay had proved adequate to maintain the adrenal cortex in hypophysectomized rats. This adrenotropic hormone was prepared and furnished through the courtesy of Dr. H. D. Moon. Ten of the hypophysectomized animals were given 10 cc of cortin daily in their drinking water; the remaining 10 did not receive cortin. In this experiment the intake of food of the 2 groups of hypophysectomized rats was regulated in order to equate the loss of weight. It was necessary to restrict the intake of food in the case of the rats which did not receive cortin to a definitely smaller amount than was consumed by those which did receive cortin. At the end of 7 days all of the animals were killed for necropsy by exsanguination. The administration of large amounts of cortin causes marked involution of the thymus in the intact rat. The loss of weight which occurred in these animals cannot he satisfactorily accounted for by the small reduction in the intake of food.

Effect of Two Steroid Compounds on Weight of Thymus of Adrenalectomized Rats.

The thymus gland of rats can be made to regress rapidly by the administration of extracts of the adrenal cortex or by the administration of some of the steroid compounds occurring in the extracts. In studies of the biologic effects of 11-desoxy-corticosterone acetate and 17-hydroxy-11-dehydro-corticosterone acetate it was noted that the latter substance was the more active of the two in producing thymus atrophy. Male rats of the Sprague-Dawley strain each having an initial body-weight of approximately 180 g were used. The diet was Purina Dog Chow. The test substances were dissolved in sesame oil and administered twice daily by subcutaneous injection. Ten normal rats were killed in order to obtain control data on thymus weights; 10 adrenalectomized rats were maintained for 7 days without treatment; 5 adrenalectomized rats were treated with 2 mg daily of 17-hydroxy-11-dehydro-corticosterone acetate; 5 adrenalectomized rats were treated with 2 mg of 11-desoxy-corticosterone; and 5 adrenalectomized rats were treated with 10.0 mg daily of 11-desoxy-corticosterone. Necropsy was performed on the 7th day. The data on body weights and thymus weights are summarized in Table I. Although 2 mg daily of 17-hydroxy-11-dehydro-corticosterone acetate did not protect the adrenalectomized rat against a loss in body weight it did produce a marked regression of the thymus. A similar dose of 11-desoxy-corticosterone acetate permitted the adrenalectomized rat to gain in weight during the period of treatment but it did not produce a significant regression of the thymus. The administration of 10 mg daily of 11-desoxy-corticosterone acetate did produce a definite loss in thymus weight but the extent of atrophy was much less than that produced by the 2.0 mg daily dose of 17-hydroxy-11-dehydro-corticosterone acetate. Selye 1 has previously observed a regression of the thymus following the administration of 11-desoxy-corticosterone to rats.

THE FUNCTIONAL INTERRELATIONSHIP OF THE ANTERIOR PITUITARY AND THE ADRENAL CORTEX

Excerpt The size and the secretory activity of the adrenal cortex are controlled to a major extent by the adrenocorticotropic hormone (ACTH) of the anterior pituitary. The anterior pituitary adjust...

Effect of Adrenalectomy During Gestation on the Size of the Adrenal Glands of Newborn Rats

The object of this study was to determine the extent to which the adrenal cortices of the fetal rat are responsive to a condition of adrenal insufficiency produced in the mother. Albino rats of the Wistar strain, each weighing 180 to 190 g at the time of mating, were used. Of 10 animals, the adrenal glands were removed on the seventh day of pregnancy and of 15 animals, on the fourteenth day of pregnancy. Eighteen additional pregnant animals were not subjected to operation. On the twenty-first day of pregnancy the young were taken for weighing either immediately after delivery or by cesarean operation. The adrenal glands of the newborn were removed and carefully cleaned of fat and connective tissue. The glands from the animals of the same sex from each litter were combined and weighed in a closed bottle by one of us who was unaware of the identity of the mother. The procedure used in obtaining glands for weighing was carefully standardized and we believe that it was sufficiently accurate to insure reliability of the differences observed. The data are summarized in Table I. The average values for the weights of adrenal glands of the newborn from adrenalectomized mothers were significantly above normal in each group represented. All of the adrenal weights for the experimental animals were above the means for normals. Histologic comparison of the glands indicated that the differences in size were owing to an increase in the amount of cortical tissue in the glands from the experimental animals. We have no proof that the glands of the fetus protected the mother against adrenal insufficiency. Mild symptoms of adrenal insufficiency were common among the pregnant mothers and we have observed, in other unpublished experiments, that a severe state of insufficiency is easily produced in these animals by mild stress, such as chilling, a 24-hour fast, and so on.

Histology and Regenerative Capacity of Liver Following Multiple Partial Hepatectomies.

Summary The capacity of liver to regenerate was maintained in rats which were subjected to partial hepatectomy 12 times within a period of one year. At the end of the experiment, only minor cytological changes were observed in the regenerated liver and there was no neoplasia.

Effect of Aspirin Upon Glycosuria of the Partially Depancreatized Rat

Summary Aspirin was administered to 7 mildly diabetic rats which were force-fed a medium carbohydrate diet. The dose was 40. 80. and 160 mg of the drug per day. A marked amelioration of the glycosuria together with a gain in weight was noted in each rat. When the drug was withdrawn, there was exacerbation of the glycosuria to significantly higher levels than were noted during the pre-injection period, and there was an accompanying loss of weight.

Subcutaneous Administration of Cortin Compounds in Solid Form to the Rat

Numerous substances having a low solubility in the body fluids have been administered experimentally by implanting them in solid form within the body tissues. We have administered to rats solid forms of extracts of adrenal cortex and 3 pure crystalline compounds which are identified in the literature as A, B, and E. 1 In Experiment 1, ten male rats having a range in body weight of from 100 to 110 g were matched into pairs and were all adrenalectomized in single-stage aseptic operations. At the time of adrenalectomy a single crystal of compound E which did not exceed 2 mg in weight was implanted subcutaneously into one animal of each pair. The 5 untreated control animals developed symptoms of adrenal insufficiency and died at intervals of 5, 6, 10, 10, and 12 days after operation. The animals which had received the single implants of compound E died at intervals of 15, 20, 23, 23, and 28 days after operation. For Experiment 2, a total extract of cortin was prepared for implantation. Compounds A, B, E, and some biologically inactive compounds were removed by fractionation. A sample of 330 cc was evaporated to dryness in a vacuum at 40°C. It was redissolved in absolute alcohol and again dried. This was repeated with acetone and the residue of 105 mg was dissolved in alcohol with 400 mg of cholesterol. The mixture was dried by warming in a stream of air. The residue was moistened with alcohol and thoroughly mixed. It was dried in a vacuum desiccator, again moistened with alcohol and compressed into pellets. Twelve male rats having body weights of from 60 to 70 g were closely matched into pairs and all were completely adrenalectomized.