Hypophysectomy

Abstract: 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.

Abstract: The direct effects of glucocorticoids on testicular LH receptor content and steroidogenesis were studied in vivo and in vitro. Immature hypophysectomized rats were treated with varying doses of dexamethasone, corticosterone, or a synthetic progestin, 17,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione (R5020). Some animals were also treated concomitantly with FSH to prevent the hypophysectomy-induced decrease in testis functions. At the end of 5 days of treatment, testicular LH/hCG receptor content was measured by [125I]hCG binding assay while steroidogenic responsiveness was measured by in vitro incubation of testes. Dexamethasone decreased testicular LH receptor in control and FSH-treated hypophysectomized rats in doses as low as 10 microgram/day, whereas corticosterone (10 microgram/day) decreased testicular LH receptor in the FSH-treated rats but had no effect in rats not treated with FSH. In contrast, R5020 had no effect on testicular LH receptor content. In vivo treatment of hypophysectomized rats with FSH increased both basal and hCG-stimulated production of androstanediol in vitro. In contrast, concomitant treatment with dexamethasone, but not R5020, decreased both basal and hCG-stimulated testicular androstanediol production. The direct effect of glucocorticoids on testicular steroidogenic potentials was also studied in primary culture of testicular cells obtained from adult hypophysectomized rats. Treatment of cultured testicular cells wtih hCG increased testosterone production. The addition of various natural and synthetic glucocorticoids, but not R5020, to hCG-treated cells decreased testosterone production in a dose- and time-related manner (triamcinolone greater than or equal to dexamethasone greater than cortisol greater than or equal to corticosterone). A 40% decrease in testosterone production was apparent at 6 h after addition of 10(-7) M dexamethasone to hCG-treated cells. These results demonstrate the direct inhibitory effect of glucocorticoids on testicular LH receptor content and steroidogenesis, suggesting the adrenal glucocorticoids may regulate testis functions.

Abstract: INTRODUCTION In 1924 Evans (25) reported that the injection of anterior pituitary extract was followed by adrenal hypertrophy. Smith (61, 62) in 1926 demonstrated that hypophysectomy induced atrophy of the adrenal cortex and that implantation of living hypophyseal tissue was followed by restoration of the gland to normal. These classical experiments established without doubt the specific tropic influence of the anterior pituitary on adrenal cortical function. Isolation of the adrenocorticotropic principle from anterior pituitary gland extract was reported by Collip in 1933 (15). In 1940 a somewhat simpler mode of preparation was described by Bates et al. (8). Further purification of the adrenocorticotropic hormone was accomplished by Evans and his group in California and Long and Sayers and their collaborators in New Haven. The former group worked with sheep pituitaries; whereas the latter used hog pitiiitaries. In 1943 Li et al. (41), employing a salt fractionation method, and Sayers et al. (56), using i...