D. C. Van Dyke

Hypothalamic Control of Pituitary Function and Corpus Luteum Formation in the Rat.

Summary and Conclusions 1. Bilateral hypothalamic lesions ventral to the ventro-medial nucleus in female rats resulted in persistent vaginal cornification in the majority of animals. Thyroid morphology and I131 uptake in obese rats with constant cornification indicated increased thyroid activity. The ovaries of those showing constant cornification contained follicles of all sizes but no corpora lutea. The interstitial tissue was not atrophic. 2. The follicles were readily converted into corpora lutea by administration of luteinizing substances, both human chorionic gonadotrophin and pituitary interstitial cell stimulating hormone. The interpretation is made that secretion of luteinizing factor by the pituitary may be impaired by small, bilateral hypothalamic lesions ventral to the ventro-medial nucleus.

Normal response to erythropoietin or hypoxia in rats made anemic with turpentine abscess.

Summary and Conclusions Rats with a turpentine abscess developed characteristic mild anemia. Such rats showed an erythropoietic response comparable to that of normal controls following treatment with human urinary erythropoietin or exposure to hypoxia. Therefore, the rat having a turpentine abscess is capable of producing erythropoietin and the marrow is capable of responding when stimulated, suggesting that the mild anemia which accompanies a turpentine abscess does not serve as an adequate stimulus for increased red cell production.

Increased erythropoietic stimulant in plasma of pregnant rats.

Summary 1. Plasma of normal adult female rats contains a factor capable of stimulating erythropoiesis in hypophysectomized and newborn rats, as judged by increased circulating red cell volume and hemoglobin. 2. This humoral erythropoietic factor is markedly increased during pregnancy. 3. Injections of plasma from non-pregnant and pregnant rats resulted in an increase in plasma and blood volumes of hypophysectomized and newborn recipients.

Inability of growth hormone to prevent the anemia which follows hypophysectomy

Summary In the search for the factor in the anterior pituitary responsible for maintenance of the circulating red cell volume, the effect of growth hormone in maintaining the red cell volume of hypophysectomized rats was investigated. Administration of doses of growth hormone sufficient to maintain a normal rate of growth for 30 days failed to prevent the development of the anemia which characteristically follows hypophysectomy.

Correction of anemia following hypophysectomy by administration of cobalt.

Conclusions The anemia of hypophysectomy was repaired by the administration of cobalt. The increase in red cell volume was of the same magnitude as that reported in normal rats. Apparently the pituitary is necessary for a normal erythropoietic response to hypoxia but is not necessary to obtain a normal erythropoietic response from cobalt. In this way the mechanisms responsible in each case appear to differ.

Differential haemopoietic response of rat and guinea pig to extracts of human urine.

In 1957, Van Dyke, Garcia and Lawrence obtained from the urine of a patient suffering from ‘erythroid hypoplasia’, a concentrate which, in the rat, appeared to possess a potent erythropoietic action. This was demonstrated by an increase in the total circulating red cells in rats after daily injections for 14 days. The increase thus obtained exceeded that following exposure for a similar period of time to a simulated altitude of 15,000 ft. As a preliminary screening test for concentrates from a number of urines, they measured the appearance of59Fe in the peripheral blood of rats, and found it was appreciably increased in animals given active erythropoietic concentrates. In view of the fact that a quantitative technique had been developed for the study of bone marrow (Yoffey, 1956) in the guinea pig, it was thought advisable to investigate the action of an active urinary concentrate by observing its action on the bone marrow. (1959).

Failure of Cobalt to Influence the Life Span of the Erythrocyte

Conclusions This study shows that the life span of the red cell is not changed in rats made polycythemic with cobalt. The mechanism for the production of polycythemia following chronic administration of cobalt must be attributed to an increase in the rate of production and release of red cells into the circulation.

Failure of Newborn Rat to Respond to Hypoxia with Increased Erythropoiesis.

Summary Suckling rats, between the age of 4 to 16 days, do not respond to hypoxia with an increased erythropoiesis as judged by increased hematocrit, hemoglobin and red cell volume.

Production of Normal-Lived Erythrocytes with Erythropoietin.

Summary Erythrocytes produced in rats under stimulus of human urinary erythropoietin have a normal survival time in circulation. This and other evidence suggest that erythropoietin administration results in production of normal erythrocytes. This evidence is compatible with the concept that erythropoietin is part of the normal mechanism controlling erythropoiesis.