Floyd R. Skelton

Studies on experimental thyroiditis.

The increasing attention directed to the role of autoimmunity in the pathogenesis of various diseases requires tha t efforts be intensified to elucidate the biological mechanisms underlying the phenomenon. For this purpose, studies of human disease are profitably coupled with investigations using experimental animals, where the immunological and pathological consequences of autosensitization can be observed under controlled conditions. Because of its resemblance to human chronic thyroiditis, experimental thyroiditis represents a particularly significant model. This autoimmune disease can be produced in several animal species including the rabbit, guinea pig, dog, rat, and mouse by injection of autologous, homologous or even heterologous thyroid protein, usually with Freund adjuvant. I t is characterized by formation of circulating autoantibodies and of delayed hypersensitivity to thyroglobulin, and by development of inflammatory changes in the animals own thyroid gland. Major problems exist in our understanding of the induction of this disease, its transfer from one animal to another, and the mechanisms actually responsible for cellular damage. The purpose of this paper is to survey briefly some current investigations underway in our laboratory on these topics.

The metabolism of progesterone-4-14C by adrenal homogenates from rats with adrenal-regeneration hypertension(1)

Abstract Progesterone-4- 14 C has been incubated with homogenates prepared from intact and regenerating rat adrenals. While corticosterone- 14 C was the major metabolite from incubations with intact adrenals, both corticosterone- 14 C and 11-deoxy-corticosterone- 14 C were identified as major metabolites from incubations of regenerating adrenals. 11-Deoxycorticosterone secretion by regenerating adrenals might explain the development of adrenal-regeneration hypertension.

Blood pressure in female and male rats following ventromedial hypothalamic lesions placed at four different ages.

Summary 1. Ventromedial hypothalamic lesions placed in female and male rats at the age of 21 and 26 days respectively, prevented the rise of blood pressure normally observed in intact rats of this age; lesions placed at the age of 59, 75 and 140 days did not show this effect. 2. Rats that had been lesioned at 59, 75 and 140 days of age ingested more sodium than their respective intact controls; this was more pronounced in the female rats than in the male animals. 3. The increased sodium intake due to hypothalamic hyperphagia may be responsible for the alleviation of the hypotensive effect of the lesions resulting from neuroendocrine deficiencies. 4. The fact that ventromedial lesions prevented blood pressure and adrenal weight from attaining magnitudes appropriate for intact controls in weanling rats only, i.e., during a phase of most active growth, suggests that the lesions interfered with the finer neuroendocrine regulation of adrenocorticotrophic hormone and perhaps growth hormone.

EFFECT OF GENTLING ON DEVELOPMENT OF ADRENAL REGENERATION HYPERTENSION IN IMMATURE FEMALE RATS.

Summary 1. Gentling acts as a stressor and increases blood pressure in adrenal-enucleated as well as intact rats. 2. At the same time gentling seems to promote growth, a paradoxical situation since growth is generally considered to be depressed by the activities of ACTH and glucocorticoids. 3. This paradox may be explained by one of the currently held concepts of the mechanism of adrenal-regeneration hypertension, namely the secretion of a hypertensive steroid other than corticosterone which is, however, ACTH-dependent.

Prevention of Methylandrostenediol, Methyltestosterone and Testosterone-Induced Hypertension in the Rat by Hypophysectomy

Summary Administration of methylandrostenediol, methyltestosterone and testosterone to hypophysectomized rats failed to produce the hypertensive vascular disease usually seen in normal animals receiving the same androgens. It is, therefore, evident that the pituitary, in addition to the adrenals, plays an essential role in the pathogenesis of androgen-induced hypertension and it is very likely that the constant stimulation of the adrenal gland by ACTH is essential to the development of such hypertensive disease. This work was supported by Research Grant HE 06975 from the National Heart and Lung Institute and by Training Grant GM 01500 from the National Institutes for General Medical Sciences, Bethesda, MD. The authors thank Mr. L. Joseph, Mrs. D. Ide, Mrs. G. Joseph, and Mrs. B. Cole for technical assistance.

Effect of Time of Reduction of Renal Mass on Development of Adrenal-Regeneration Hypertension.∗

Summary 1. Salt-treated, uninephrecto-mized-adrenalectomized and contralaterally adrenal enucleated female rats in which those operative steps are performed shortly after weaning (zero time) show a higher mean terminal blood pressure and greater enlargement of heart, kidney, brain and spleen than do similar rats that are operated on 2 weeks after zero time. 2. Performance of the uni-nephrectomy 2 weeks after uniadrenalectomy and adrenal enucleation results in significantly lower terminal mean blood pressure and correspondingly lower lesion severity indices. This suggests that the enucleation step proper is the crucial operation in bringing about the full severity of the hypertensive syndrome. 3. Uninephrectomy and uniadrenalectomy on day zero and contralateral enucleation of the compensatorily-hypertrophied adrenal 2 weeks later results in mean terminal blood pressure and lesion severity indices comparable to those rats in which these operations are carried out at zero time. Blood pressure only rises steeply after the hyper-trophied adrenal gland is enucleated. 4. It is concluded that, while reduction of renal mass contributes greatly to the development of this form of experimental hypertension, enucleation of the adrenal is the decisive step. It is further concluded that this combination of operations early in infancy finds a more favorable internal environment for the development of severe hypertensive cardiovascular disease.

Effect of ventromedial hypothalamic lesions on development of adrenal-regeneration hypertension in weanling female rats

Ventromedial hypothalame Läsionen hemmen die NNR-Regenerations-Hypertonie. Dabei ist nicht eine Verschiebung in der Nahrungs- oder Elektrolyt-Aufnahme verantwortlich19,20.