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C HUGGINS

Publications and source records attributed to C HUGGINS.

At least 37 records · Page 2Linked to original sources
PubMed1960

Disturbed reproductive function following section of the portal vein.

Integrity of the portal vein is a condition for normal function of the reproductive tract in female rats. Section of the portal vein (PVS) always abolished periodic sexual function. In a series of 23 animals, 6 developed continuous estrus and other signs of the presence of excessive amounts of estrogenic hormones; yet the ovaries of these rats were small. In 6 other rats there was growth of the prostate and additional evidence of increased activity of androgenic hormones. Many rats failed to become pregnant and nearly all pregnant rats aborted. Except for a decrease in lipid content, the composition of the liver of PVS rats resembled that of intact mates in the criteria which were applied. The rapid passage of blood through the liver is necessary to conjugate the excessive amounts of steroids which the rat ovary normally produces and an intact portal vein is an essential unit in the mechanism necessary for their partial inactivation.

Animals↗
PubMed1959

Influence of hormones on liver. I. Effects of steroids and thyroxine on pyridine nucleotide-linked dehydrogenases.

Modification of the endocrine milieu intérieur by administration or withdrawal of hormones considerably influenced the concentration in liver of lactic dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconic dehydrogenase. Hormones effective in this regard are thyroxine, estradiol-17beta, dihydrotestosterone, and 3alpha-hydroxysteroids in the androstane series. These hormonal effects are both organ-selective and, in liver, enzyme-selective. Thyroxine and steroids are not equivalent in their influence on the 3 hepatic dehydrogenases. Thyroxine was preeminent in this regard among hormones investigated in the present experiments. Each of the pyridine nucleotide-linked dehydrogenases in liver had an individually characteristic response to the administration of various hormones which was reflected in its hepatic level. The concentration in liver of lactic dehydrogenase was profoundly raised or lowered, respectively, by the administration of thyroxine or by thyroidectomy, and injection of steroids had small influence on its level. The levels of glucose-6-phosphate dehydrogenase and of 6-phosphogluconic dehydrogenase were considerably influenced by injection of thyroxine, estradiol-17beta, or testosterone. Sex steroids did not increase the levels of these enzymes in hypophysectomized or thyroidectomized rats unless thyroxine was administered concurrently. Under designated conditions, it was found that the concentration of 6-phosphogluconic dehydrogenase was increased by hormonal methods which did not elevate the concentration of glucose-6-phosphate dehydrogenase. But high levels of glucose-6-phosphate dehydrogenase were not achieved without a considerable elevation of 6-phosphogluconic dehydrogenase as well.

Animals↗
PubMed1959

Rapid induction of mammary carcinoma in the rat and the influence of hormones on the tumors.

A study was made of the optimal conditions for the induction of mammary cancer in the rat. 3-Methylcholanthrene was administered via the gastrointestinal tract, and a simple technique was worked out for inducing mammary cancer regularly and rapidly. Under conducive conditions, which were readily reproduced, multiple mammary carcinomas and these tumors only were induced in every rat in repeated experiments in 60 days or less. In the strain of animal employed in the present experiments, the rapid induction of mammary cancer proved to be a function of (a) dosage, (b) the timing of administration of the aromatic hydrocarbon, and (c) a favoring hormonal status of the recipient. Most of the established tumors were hormone-dependent because they diminished markedly in size after hormone withdrawal through ovariectomy or hypophysectomy. Similar regression of the tumors was frequently achieved by the administration of dihydrotestosterone. Shrinkage of the cancers was accompanied by atrophic changes. Experimental mammary tumors with these physiologic characteristics have not been recognized hitherto. The minority of mammary cancers continued to grow after ovariectomy; these are hormone-independent tumors and tumors of this sort had a characteristic cytologic appearance following modification of the endocrine state. The cell population of a single tumor was not always uniform in its response to appropriate hormonal modifications. In certain tumors in response to changes in the endocrine status of the host many of the cells underwent atrophy whilst other adjacent cells in the same tumor continued to grow so that the net result was a hormone-independent tumor. Hypophysectomy was the most effective method found to induce regression of mammary cancer in the present experiments.

Animals↗
PubMed1958

Effect of 3-methylcholanthrene on the endocrine system and metabolism of the rat and its influence to retard growth of mammary tumors hitherto refractory.

The repeated administration of 3-methylcholanthrene to adolescent rats resulted in (a) a profound, incomplete, and selective depression of certain hypophyseal functions; (b) decreased growth of transplanted mammary tumors; and (c) a retardation of body growth. Only the last mentioned effect was reversed by forced feeding. The retarded rate of body growth induced by 3-methylcholanthrene was prevented by the concurrent administration of dihydrotestosterone or progesterone, or by ovariectomy; rats so treated became overweight despite the injection of 3-methylcholanthrene. Phenolic estrogens intensified the retardation of body growth induced by 3-methylcholanthrene and emaciation resulted. The administration of 3-methylcholanthrene resulted in decreased gonadotrophin production by the pituitary and the ovaries were more drastically affected by the depression of pituitary activity than the adrenals were. The compound exerted differential effects on the pituitary glands of males and females respectively. Hormonal functions of both ovary and testis were decreased in rats treated with 3-methylcholanthrene but, whilst ovarian weight was much reduced, the size of the testis was not decreased and the germinal epithelium of the male was little affected by the treatment in most instances. There was a considerable reduction of the content of alkaline phosphatase in the breast of intact rats treated with 3-methylcholanthrene but atrophy of the mammary epithelium did not occur and hyperplasia of the mammary tree was often observed. The administration of 3-methylcholanthrene considerably slowed the growth of transplanted mammary tumors characterized by high dependence on hormones and the concurrent administration of gonadotrophin restored the growth rate of the tumors. The administration of 3-methylcholanthrene or androstan-17beta-ol-3-one was only moderately effective in controlling the growth of transplanted mammary tumors characterized by low hormonal dependence; the combined administration of these compounds was highly efficacious in retarding the growth of these refractory tumors. 3-Methylcholanthrene partially retarded the growth of mammary fibroadenomas in hypophysectomized rats.

Animals↗
PubMed1957

Hormonal influences on mammary tumors of the rat. II. Retardation of growth of a transplanted fibroadenoma in intact female rats by steroids in the androstane series.

Many members of the androstane series profoundly retarded the growth of a transplanted benign mammary fibroadenoma of the rat; the restraint of tumor growth was in direct proportion to the amount of the administered compound until its maximal effect was achieved. Certain steroids closely related to the androstane inhibitors accelerated the growth of the tumor. These effects of divergent sort depend on the molecular structure of the steroid. The molecular structure of androstane derivatives, which is of high significance in modifying the rate of growth of the benign mammary tumor, consists of multiple components. These include (a) the presence and number of ketone and hydroxyl groups in special orientation at specific sites, (b) the sites of dehydrogenation in the molecule, and (c) the presence, number, and state of hydrogenation of alkyl groups at designated molecular positions. These multiple factors determine whether androstane compounds will inhibit growth of the tumor, enhance it, or fail to influence its growth. The androstane compounds which caused either the restraint or the promotion of tumor growth had the common property of inducing proliferation of the normal mammary epithelium. Two mechanisms are involved in the restraint of growth of mammary fibroadenoma by androstane inhibitors. The primary effect is the abolition of action of phenolic estrogens and progesterone when dihydrotestosterone is administered concurrently, presumably through direct action at the tumor cell level A secondary contributory suppressive effect is the depression of ovarian activity, and consequently of the production of phenolic estrogens and progesterone, by these compounds. Transplanted mammary fibroadenoma in the rat possesses neoplastic traits and also some growth properties of normal mammary epithelium; inhibition of these latter by hormonal methods commonly retarded the growth of the tumor. But in hypophysectomized rats dihydrotestosterone failed to inhibit the growth of a mammary fibroadenoma with unusually low hormonal dependence as determined by functional tests of its growth.

Androgens↗
PubMed1956

Hormonal influences on mammary tumors of the rat. I. Acceleration of growth of transplanted fibroadenoma in ovariectomized and hypophysectomized rats.

A transplanted mammary fibroadenoma was found to grow in 95 per cent of intact adult female rats and the increment of tumor weights was progressive and logarithmic. The growth of the tumor was retarded by ovariectomy and still more when this was combined with adrenalectomy. In ovariectomized rats the growth of the tumor was stimulated by phenolic estrogens, this increase being enhanced when progesterone was added. In these responses to hormonal changes the mammary gland and the tumor resembled each other. Yet there are many differences between the growth of the fibroadenoma and that of the mammary gland. In contrast to the progressive growth which occurred in intact adult females there was a prolonged period of indolent growth of transplants in hypophysectomized rats; but after many weeks active growth began and the tumors eventually reached large size. During the period of quiescent growth the tumor was cytologically atrophic but after the growth spurt had started the microscopic appearance of the fibroadenoma resembled that of tumors growing in normal adult females. The mammary gland remained atrophic during both the slow and the accelerated phases of tumor growth, and so too with the other secondary sex expressions. In hypophysectomized rats estrone and progesterone, when combined, stimulated the growth of the tumor, and this growth was accelerated by the additional administration of lactogenic or growth hormones. None of these hormones, separately, stimulated the growth of the tumor. In ovariectomized rats other differences were demonstrated between the growth of the mammary gland and the fibroadenoma. Progesterone, injected alone, accelerated the growth of the tumor but not that of the mammary glands. The administration of phenolic estrogens exerted a biphasic effect on the growth of the tumor whilst that on the breast of its hosts was monophasic. With progressively increasing doses of these phenols there occurred primarily an augmentation of the rate of growth of the tumor until a peak was achieved; an increase of the dose above the optimal amount depressed the growth of the tumor. The stage of depression of growth was not observed in the mammary glands of these tumor-bearing rats. Many steroids which induced gestational changes in the mammary gland accelerated the growth of the tumor. Among these were estrone and progesterone in combination and 17alpha-ethinyl-19-nor-testosterone administered alone. But gestational changes developed in the mammary gland of rats treated with 4-androstene-3alpha,17beta-diol, without growth of the tumor. The evidence which we have presented proves that the mammary fibroadenoma tested had some of the functional properties of a normal mammary gland, and neoplastic traits as well. In its response to hormones it had characteristics which set it apart from all other endocrine targets of the rat.

Adenofibroma↗