Robert A. Liebelt

Nychthemeral variations in plasma free corticosteroid levels of the rat.

Summary Nychthemeral variations in levels of plasma free corticosteroids in the rat have been observed, with highest concentrations of steroid between 4 p.m. and midnight. The magnitude of these cyclic variations is such that they will have to be considered in measurement of “resting levels” of plasma corticosteroids in this species.

REGULATORY INFLUENCES OF ADIPOSE TISSUE ON FOOD INTAKE AND BODY WEIGHT

The influence of genetic, hormonal and neurogenic factors on the cellular component and lipid content of two specific fat organs in non-obese and obese inbred mice was recently described.’ It was suggested that genetic factors possibly intrinsic to adipose tissue imposed a specific developmental pattern upon the grossly organized components (fat organs) of the adipose tissue of the body in terms of lipid content and lipid-free mass. However, this genetic regulation appeared to be intimately related to hormones and neuroregulatory mechanisms. The data further suggested that no single specific fat organ was critical in the relationship between appetite regulation, weight gain and fat organ metabolic activity; but rather the “total mass” of adipose tissue distributed throughout the body was the important consideration in any postulated regulatory mechanism. The following series of experiments were carried out to further investigate the inter-relationships between lipid content of individual fat organs, total body lipid content as reflecting the total adipose tissue mass, food intake regulatory mechanisms and the development of obesity in the mouse.

Sensitivity to electric shock after ventromedial hypothalamic lesions.

Abstract Bilateral ventromedial hypothalamic lesions were produced in mice with gold-thioglucose and in rats with electric current. Shock thresholds were measured in both species of animals. Animals with lesions showed markedly lower shock threshold levels than the control subjects. Lesions in the ventromedial region of the hypothalamus may alter the emotionality of the animals and increase or escalate its response to noxious stimuli.

Extra-hypothalamic lesions associated with gold-thioglucose induced obesity.

Conclusion Goldthioglucose administration to inbred C57 Black and CBA mice, in amounts sufficient to induce hyperphagia and massive weight gain, results in lesions of nuclei adjacent to the area postrema of the medulla oblongata, to the median eminence of the hypothalamus, to the supraoptic crest between the hypothalamus and the basal telencephalon, and between the subcommissural and subfornical organs associated with the midbrain-epithalamic transition and the hippocampal formation. The hypothesis is advanced that the observed distribution of the lesions is related to deficiency of the blood-brain barrier at these sites.

Hypothalamic lesions associated with goldthioglucose-induced obesity.

Summary The response to goldthioglucose-induced obesity differs in two genetically independent inbred strains of mice (CBA and C57BL). This difference in response to a specific dose is associated with degree of hypothalamic damage, more extensive in CBA than in C57BL mice, the former becoming more obese than the latter. Even when hypothalamic lesions comparable to those induced in very obese CBA mice are obtained by relatively large doses of goldthioglucose in C57BL mice, weight gain is approximately one-half of that appearing in CBAs. Lesions of the fornix also occurred in CBA but not in C57BL mice; these lesions may be related to the greater weight increment in CBA mice. A further possibility is a genetically controlled (peripheral) metabolic difference in reaction to hypothalamic lesions in these 2 inbred strains.

Motivation and learning in mice after goldthioglucose-induced hypothalamic lesions

Shock-avoidance training was given to normal mice and to mice with goldthioglucose-induced lesions in the ventromedial region of the hypothalamus. The lesioned mice learned faster than the control mice. Lesions in the ventromedial region of the hypothalamus may alter the emotionality of an animal and thus its motivation during learning.

LOCALIZATION OF SULFHYDRYL AND DISULFIDE GROUPS OF PROTEIN IN PANETH CELL SECRETION OF THE MOUSE INTESTINE

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Goldthioglucose-induced hypothalamic lesion and ACTH release.

Discussion and conclusions The increase in plasma corticosterone resting levels seen in the first few days after injection of GTG may be due to one or several mechanisms: alteration of the conjugation capacity of the liver(18) due to the drug itself or accompanying the diminished food intake that immediately follows GTG injection(6), thus leading to increased plasma concentrations of free Cpd. B; or actual stimulation of the hypothalamic centers related to ACTH release by development of the hypothalamic lesion. These results show, at any rate, that the hypothalamic lesion produced in CBA mice by the dose of GTG used in this study does not inhibit release of ACTH normally produced by exposure to stress. Animals with this type of hypothalamic lesion, therefore. cannot be used for an assay of CRF.

Species and Strain Dependence of the Response to a Granulocytosis-Promoting Factor (GPF) Extracted from a Mouse Tumor.

Summary Marked strain differences were observed in the degree of granulocytosis which could be induced in both mice and rats by a partially purified granulocytosis - promoting factor (GPF) extracted from a transplantable mouse tumor, CE 1460. The strain differences appeared to be reflected in both the normal leukocyte range and the response to isotonic saline, parameters from which the strain-specific response to GPF could apparently be predicted. It was postulated that the active principle in GPF may be the same as that present in “leukopoietin” preparations from plasma and tissue sources. Furthermore, it was hypothesized that the greater granulocyte release promoted by GPF, as compared to that promoted by “leukopoietin”-rich preparations, might conceivably be due 1) to species or strain differences in the bioassay systems or 2) to a greater concentration of the active (granulocytosis-promoting) principle and/or a lower concentration of a theoretical granulo-cyte-release inhibiting substance in the partially purified GPF prepared by our method or 3) to a combination of these factors. These results indicate that genetic (strain and species) differences should be taken into consideration in evaluating the biologic activity of GPF and possibly also of “leukopoietin.”