Mary M. Garrison

Decreased binding of insulin to its receptors in rats with hormone induced insulin resistance

Abstract Insulin and glucagon receptor binding was studied in purified liver membranes from rats made insulin resistant by implantation of an MtT pituitary tumor which secretes growth hormone, prolactin, and ACTH. Insulin binding to its receptors was decreased and correlated with the degree of insulin resistance. In contrast, binding of glucagon to its receptors was unchanged.

A structural analysis of hepatomegaly induced by a hormone-secreting tumor

Abstract The hepatic growth observed in rats bearing transplantable hormone (ACTH, growth hormone, prolactin) secreting mammotropic tumors (MtT.F4) has been resolved into three components: (1) an increase in the size of individual parenchymal cells relative to the amount of DNA which they contain; (2) an increase in the DNA contents (ploidies) of the parenchymal cells and of their nuclei; and (3) an increase in the total number of parenchymal cells. As a result of all of these factors, the relative mass of the liver is increased to an extent greater than would have been expected to result from normal growth. Following removal of the tumors there is a reversal of all of these changes, except for a persisting increase in cell number and DNA content, and the resulting cells are smaller than normal. Whereas fatty metamorphosis and other degenerative changes occurred in the latter stages of tumor growth, the initial response was a striking hepatocellular enlargement and proliferation without significant fatty change. Fine structural studies of changes present in livers following 7 weeks of tumor growth showed many enlarged parenchymal cells containing proportional increases in all cytoplasmic constituents. Some cells, generally located at the lobule periphery, were heavily laden with fat vacuoles or showed almost complete fragmentation of the rough endoplasmic reticulum with formation of ribosome-studded vesicles containing material that was apparently secretory in character. Other fine structural changes included an increase in free ribosomes and polysomes and mitochondrial enlargement with the occasional appearance of very large bizarre mitochondrial forms. All changes, except possibly for a slight increase in relative liver mass, were prevented by adrenalectomy of the animal prior to tumor growth.

Comparison of Two Different Transplantable Mammotropic Pituitary Tumors. Hormone Content and Effect on Host

Summary A pituitary tumor (7315a) from a rat treated with 2,4,6-trimethylaniline was transplantable. Studies during the eighth and twelfth transfer generation of 7315a showed the tumor to be similar to the mammotropic tumor MtT F4 established by Furth in that it contained the same 3 pituitary hormones, which produced similar changes in the organs of the host. MtT 7315a and MtT F4 contained the same concentration of prolactin (2 IU/g dry weight) but MtT F4 contained more than 10 times the, concentration of growth hormone and ACTH found in MtT 7315a, Correspondingly rats with MtT 7315a grew less rapidly and had less hypertrophy of the liver, kidney and preputial gland than rats with MtT F4, but the mammary glands were larger. Both tumor lines induced equally large adrenals (9 X normal) and blood levels of corticosterone (8 X normal) but the ascorbic acid concentration of the adrenal was different (7315a: 94 vs F4: 180 mg/100g) due to difference in growth hormone levels.

Hormonal Interactions Among GH, ACTH, Cortisol and Dexamethasone upon Size of Kidney, Liver, and Adrenal

Summary A ZnACTH preparation of ACTH was found to be nearly 10 times more effective than the Acthar gel preparation as a stimulator of increase of adrenal weight but the two preparations were equally effective as stimulators of weight increase of the kidney and liver. Bovine GH (5 mg/day) had little effect on adrenal, kidney or liver weight. When injected with either ACTH preparation the BGH further increased the adrenal weights. Either cortisol or dexamethasone also increased the effectiveness of Acthar on adrenal weight, and when BGH was injected as a third hormone a further adrenal weight increase was observed suggesting three different mechanisms of action. Kidney weights were increased by cortisol (15 mg/day), dexa (200 μg/day) or Acthar (100 IU/day) to about the same extent. The addition of BGH (1 or 2 mg/day) reduced by more than one half the dose of the adrenal hormone required to produce a given kidney weight. Liver weights were increased by ACTH, cortisol and dexa. BGH increased the effect of each of these hormones on liver weight. When ACTH was injected a linear correlation between adrenal weight and kidney weight was again demonstrated but different slopes were obtained with ZnACTH and Acthar. These data further indicate the importance of hormones and the complexity of their interaction (hormonal balance) in controlling size of various major organs and tissues in the body.

Daily changes in concentration of pancreatic and serum insulin and of blood glucose during 5 days of treatment of rats with growth hormone, ACTH, cortisol, dexamethasone, and tolbutamide alone and in combinations

Abstract Rats with or without 0.5% tolbutamide in the diet were injected over a 5-day period with growth hormone, ACTH, cortisol, dexamethasone, or various mixtures of these diabetogenic hormones and the daily alterations in blood glucose (BG), serum (SI), and pancreatic insulin (PI) concentrations followed as well as glucosuria. GH (5 mg/day) increased the insulin concentration in the pancreas and serum without affecting blood glucose. ACTH (80 IU/day) decreased PI and increased SI with only a slight increase in BG. Cortisol and dexamethasone decreased PI and increased SI and BG. The severalfold increase in SI with glucocorticoids always preceded the increase in BG by 12–24 hr. Mixtures of GH with the glucocorticoids increased and quickened the rise in BG and SI and the falls in PI, but the rise in SI always preceded the rise in BG by several hours. During multiple hormonal treatment, PI decreased in magnitude usually for 3–4 days but by the fifth day tended to revert toward normal, showing adaptation. In contrast, BG and SI tended to remain elevated and glucosuria persisted. These data suggest that in spite of the high concentrations of diabetogenic agents used compensatory changes were made by the rat with intact pancreas over a period of 5 or more days. This hormonally induced condition of elevated SI and BG but normal PI is characteristic of insulin resistance. Tolbutamide by itself decreased PI without a rise in SI (except for a temporary increase at 4–8 hr after the first injection) and with only a minor decrease in BG. Most of the changes due to the hormones were accentuated in rats with 0.5% tolbutamide in the diet, suggesting that tolbutamide is diabetogenic because it decreases PI.

Constant relation between blood level of thyrotropin and total thyrotropin in thyroidectomized mice.

Summary In thyroidectomized mice approximately the same relationship exists between the blood level of TSH and total amount of TSH in the TSH-producing pituitary tissue in the body whether this tissue is in situ in the sella turcica or in a tumor in the hind leg, and while the amount of TSH in this tissue varies by 10,000 times from an amount of 20 milliunits to 200 units. These results demonstrate clearly and quantitatively the autonomous release of pituitary TSH independent of any hypothalamic influence. In these mice the units of TSH/ml of blood times 40 gives an approximate measure of total TSH in units in the body. Thyroxine treatment caused a parallel lowering of the level of TSH in blood and tumor.