Frederick E. Emery

Progesterone in Adrenalectomized Rats

Summary Our results confirm previous reports that progesterone will keep adrenalectomized rats alive. 1 , 2 , 12 In our colony, after 2-stage adrenalectomy, doses of one milligram daily or less were usually adequate to keep young, newly-weaned, female rats alive and showing some gain in weight throughout the treatment period.

Duration of Estrus in Ovariectomized and Adrenal-Ovariectomized Rats Before and After Theelin

Within the last few years numerous papers have appeared on several phases of the adrenal problem without adding, as Rogoff 1 has recently discussed, any very definite contribution. The literature on the sex-relationship has been especially confusing; and the many references cited by Kroc and Martin 2 indicate that total adrenalectomy may cause no change, a slight modification or complete inhibition of the estrus cycles. These authors made a point of the fact that the weight-loss of adrenalectomized rats must be restored before normal estrus is again established following injections of the cortical hormone. Yet this same result, as to normal estrus in adrenalectomized rats, may be obtained by allowing the animals to drink salt solutions (Kutz, et al. 3 ). This led us to study, by a different procedure, the theelin-inhibition problem previously reported. 4 The present approach has been first, to compare ovariectomized and adrenal-ovariectomized rats as to the estrus occurring on successive days following the operation; and second, the duration and reoccurrence of estrus that followed various doses of theelin. The estrus cycles were taken daily, by the pipette method, for 2 weeks or longer preceding and following the operation. Six to 10 days following the operation, all rats were placed on Ringers solution as their only source of drinking water. A few animals died before the sixth day; but these are not considered in the data. All animals were autopsied. In 4 of the 60 rats composing the adrenal-ovariectomized group, adrenal fragments were found. Ovarian fragments were not seen in either group. The per cent of rats in estrus each day for 10 days before and 12 days after ovariectomy (group O) is shown in Fig. 1; and similar results for adrenal-ovariectomized rats (group A-O) are found in Fig. 2. The 2 figures are almost identical in every way.

Experimental Hypertrophy of the Adrenal Glands

The relationship between the hypophysis and the adrenal glands which has long been known to exist in clinical cases, 1 has not been well understood. Experiments in animals have thrown considerable light on this subject especially in regard to a pituitary substance necessary for normal adrenal function. 2 Many studies on pituitary implants and extracts in relation to the reproductive system have been made in recent years but the effects on the adrenal glands, when reported, were not significant. In immature rats implanted with pituitary glands of castrated rats some hypertrophy of the adrenals was noted at autopsy but the results were not outstanding. 3 Recently we have continued these studies and have arranged the experiments to show the effects of the cortico-adreno-tropic substance of the pituitary. The results have been very striking and consistent. Albino rats weighing about 150 gm. were divided into 2 groups of equal weight; one group consisted of 35 controls which were not injected; the other group consisted of 35 rats which were injected daily for 10 days with an extract of the pituitary gland. On the eleventh day the rats were killed and the adrenals weighed. The hypertrophy of the adrenal glands produced in the injected group amounted to as much as 150% and as little as 20% in the individual rats. Accurate determinations show that this hypertrophy is largely confined to the cortex which consists of cells larger than normal and more filled with lipoid material. Experiments with the growth hormone of the pituitary showed some enlargement of the adrenals but the effects were slight in comparison with whole pituitary extract. The thyroid gland was not increased in size.

The Anterior Pituitary Sex Hormone of Normal and Semicastrated Rats

Summary The amount of anterior pituitary sex hormone in the pituitaries of normal male and female rats was not noticeably changed after semicastration. This hormone has not been found in the blood serum of normal or semicastrated nullipara females, or in normal or semicastrated males. The need for a greater amount of the hormone in the Mood of semicastrated animals is pointed out.

Effects of Splenectomy on Pituitary Gonadotropic Substances

Summary Tests with pituitary grafts of minimal strength failed to show that splenectomy was concerned with: (1) summation effects of ovarian weights produced by repeated grafts over a period of 25 days, (2) the amount of ovarian response obtained at the end of 5 days, (3) the potency of the pituitary gland of the donor, or (4) the inhibition of estrus following sexual maturity induced by pituitary grafts.

Vasomotor Control of the Liver Circulation

Our present knowledge of the vasomotor control of the liver circulation is curiously inadequate. In due time the evidence for this conclusion will be reviewed in detail; now we wish merely to record a summary of the results which have been obtained during the last couple of years in a study of this problem, using cats under chloralose anesthesia and the liver plethysmograph previously referred to. 1 , 2 The peripheral vagus has no effect on liver volume; we have stimulated it in the neck (after denervating the heart according to Cannons method), below the heart in the thorax and after emerging through the diaphragm. The postganglionic fibers of the hepatic plexus constrict not only the terminals of the hepatic artery but also those of the portal vein. The preganglionic fibers of the splanchnic (left) have exactly the same effect on liver volume, either by way of the artery or portal vein, as stimulation of the postganglionic fibers in the hepatic plexus. Reflex pressor responses are accompanied by decreased liver volume; depressor reflexes produce dilation in the liver. If, however, the liver is denervated by cutting the fibers of the hepatic plexus, its volume then follows passively the general blood pressure. During the generalized vasomotor activity induced by asphyxia (rebreathing the air in a small balloon) the liver constricts powerfully during the rise of general blood pressure and remains constricted even as the heart begins to fail. If it is denervated, however, it dilates for a time as the general blood pressure is rising; but before this has reached its maximum the liver often begins to constrict maximally. This delayed constriction may be prevented by removal of the adrenals; then the denervated liver volume passively follows the general blood pressure throughout the course of the asphyxia.

Effect of Adrenalin and Pituitrin on the Volume of the Liver.

In view of the contradiction which exists in the literature in regard to the effects of adrenalin and pituitrin on the circulation in the liver, we have used the liver plethysmograph, which has been previously described, 1 in a new attack on this problem. The results will be very briefly described in this preliminary report without substantiation from actual records or attempt to cite the literature; these will appear in due time. Cats and rabbits under chloralose anesthesia have been used in this work; the results are as follows: I. Intravenous injections of adrenalin. 1. Pressor doses invariably produce constriction in the liver, whether introduced by way of the femoral, or portal veins, or hepatic artery, provided the general blood pressure is high and the animal in good condition. This constriction may last as long as the pressor response or it may at times give way to prompt and active dilation; when this latter occurs it may be abolished by section of the depressor nerves (rabbit). On the other hand, if the animal is in poor condition with low blood pressure the liver apparently dilates passively during the pressor response to an injection by way of the femoral vein. This is intensified by first clamping the hepatic artery, but is prevented altogether and even replaced by constriction if the portal vein has been previously clamped so as to restrict the volume changes in the liver to variations in its arterial blood supply; i. e., the liver is forced to expand under these conditions and in spite of active vasoconstriction within itself, because of an engorgement through its massive portal supply. This in turn is probably due to an unusual movement of blood through the toneless (?) mesenteric capillaries as a result of the high general blood pressure.

Augmentation of Gonad Stimulating Hormone of the Hypophysis by Copper

In a recent report 1 it was shown that zinc sulphate in combination with antuitrin S augmented the weights of the ovaries of immature rats above that obtained with antuitrin S alone. In contrast to this, zinc sulphate had no augmentative effect when given in combination with pituitary implants. Copper, on the other hand, seems to differ from zinc in certain of these ovarian augmentative reactions. Fevold, et al., 2 obtained ovulation in rabbits by intravenous injections of copper salts but failed to do so with zinc. In these rabbits the copper may have altered the response of the gonad stimulating hormones present in the blood. It, therefore, seems likely that a similar mechanism might be induced in immature rats by combinations of copper salts and pituitary implants. The data on this point are described in the present study. The recipients were albino rats of approximately 38 gm. body weight. All donors were normal adult male rats. The pituitary implants were made in the abdominal cavity under ether anesthesia. Copper sulphate was given intraperitoneally once or twice daily in doses up to one-third of a milligram at a time in one cubic centimeter of saline solution. The ovaries were removed 5 days after the implants were made. One normal male pituitary increased the average weight of both ovaries from 13.0 mg. (controls) to 17.0 mg. (groups A and B, Table I). Under the same treatment but with copper sulphate the ovaries weighed 22.3 mg. (group C). In this group the distribution of the ovarian weights was more even throughout the range while in those without copper (group B) in only 2 cases were the weights above 24 mg. The median like the mean was higher in the copper treated group but the differences are small and not statistically significant.

CIRCULATORY EFFECTS OF DIETHYLSTIL –BESTROL IN CATS AND RATS WITH A NOTE ON INTESTINAL ABSORPTION

THE PRESENT REPORT deals with the changes in blood pressure and heart rate induced by diethylstilbestrol administered intravenously and by intestinal absorption. The data show that the amount of diethylstilbestrol necessary to change the blood pressure is greater than the largest doses used for estrogenic action. Twenty–two cats and 20 rats were used. Approximately one-half of the cats were females, whereas all of the rats were castrated females. The experiments were acute and lasted as long as 6 hours for the cats but not more than 30 minutes for the rats. The animals were anesthetized with urethane and nembutal. Twenty-two cats and 20 rats were used. Approximately one-half of the cats were females, whereas all of the rats were castrated females. The experiments were acute and lasted as long as 6 hours for the cats but not more than 30 minutes for the rats.The animals were anesthetized with urethane and nembutal.

Treatment of Bartonella muris Infections with Sulfanilamide

Summary Splenectomized rats infected with Bartonella muris were treated with sulfanilamide in doses of 500 mg per kilo of body weight. A study of 30 rats thus treated showed that the treatment had no detectable effect on Bartonella muris. The toxicity of the sulfanilamide seemed to be a factor contributing to the mortality.