Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymes involved in conversion of pregnenolone to testosterone in Leydig cell tumors showed a wide distribution among smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), and cytosol, while these enzymatic activities in normal testes were associated primarily with smooth endoplasmic reticulum. Progesterone, used as a substrate in the presence of an NADPH-generating system, was metabolized to androstenedione and finally to testosterone by microsomes from some strains of tumor which did not form testosterone from exogenous labeled androstenedione. Treatment of microsomal membranes from normal testes with 0.1 M Ca++ and Mg++ caused a marked decrease in 17 beta-dehydrogenase activity, measured as conversion of exogenous [3H]androstenedione to [3H]-testosterone, without serious effects on activities of 3 beta-ol-dehydrogenase or 17 alpha-hydroxylase. Studies of initial velocity kinetics showed that treatment with magnesium ion resulted in a marked reduction in affinity of androstenedione for 17 beta-dehydrogenase while the maximum velocity was the same as in untreated microsomes. Also, experiments using [14C]progesterone and [3H]androstenedione simultaneously as substrates demonstrated that treatment with Mg++ ion made it more difficult for exogenous [3H]androstenedione to reach the active site of 17 beta-ol-dehydrogenase than [14C]androstenedione formed in the microsomal membrane from [14C]progesterone. Microsomal proteins were more easily solubilized and 3 beta-ol-dehydrogenase was more severely influenced by Mg++ ion in tumor membranes than in normal microsomes.
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PMID:The possible roles of membrane organization in the activity of androgen biosynthetic enzymes associated with normal or tumorous mouse Leydig cell microsomes. 3 99

Cells of sarcoma 180 and of Ehrlich's carcinoma were maintained by serial transplantation in male and female Swiss mice. Either estrogen, progesterone, or testosterone were injected im at doses of 1 mg/mouse. Ascitic fluid was aspirated at intervals of 1, 3, 6, 24, and 48 hours following hormone injections. Enzyme activities were analyzed by subjective grading according to the intensity of staining reaction. Estrogen produced enhancement of alkaline phosphatase activity in both types of cells in both sexes of mice. Progesterone produced increased alkaline phosphatase activity in both types of cells from female hosts but an inhibitory effect in male hosts' cells. Testosterone produced no change in enzyme activity in tumor cells of female hosts but in male hosts it inhibited enzyme activity of sarcoma 180 cells and activated activity in carcinoma cells. The effect of all 3 hormones on acid phosphatase activity was activation. With adenosine triphosphatase, estrogen stimulated the activity in both types of tumor in both sexes. Progesterone stimulated cells from male hosts with little or no effect on cells from female hosts. This enzyme was resistant to testosterone. Succinate dehydrogenase activity under similar conditions was different. Estrogen reduced this activity and progesterone produced some inhibition of activity. Testosterone inhibited the sarcoma cells but had no effect on carcinoma cells of either sex. Others have shown that sex hormones affect the enzyme activities beyond the target tissues, particularly in the liver, kidney, and pancreas. Different responses of the enzymes seemed to depend on the endogenous hormonal status of the mice.
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PMID:Enzymatic responses of transplanted tumour cells towards estrogen, progesterone and testosterone. 13 8

High dosage MAP (medroxyprogesterone acetate) was used in the treatment of very advanced breast cancer. 25 patients were included in the study all of whom had measurable lesions which had been unsuccessfully treated by other methods, hormonal or combination chemotherapy. Tables present information on previous treatments, results of pre-MAP therapy examinations, and results of post-MAP therapy examinations. Treatment dosage is explained. Results with this high MAP-dosage therapy compare favorably with the rate of remission obtained through other primary hormonal therapies by other researchers. Promising results without noteworthy adverse effects were obtained; remissions, however, were short. 7 of the 25 had partial remission with a median duration of 5+ months. Another 7 patients obtained a stationary status of the disease. Even some patients who had not responded previously to Tamoxifen achieved partial remission with MAP therapy, indicating that the MAP does not operate directly on the tumor cells. The incidence of partial remissions was not adversely affected by previous combination chemotherapy and hormonal treatment. Acceptability of the treatment was good.
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PMID:High dose medroxyprogesterone-acetate treatment in advanced mammary carcinoma. A phase II investigation. 16 70

Characteristics of [3H]progesterone-binding components were studied in cell-free preparations of two hormonally responsive tumors: the R3230AC mammary adenocarcinoma and 9,10-dimethyl-1,2-benzanthracene-induced mammary tumor of the rat. Progesterone-binding macromolecules from cytosols of both mammary neoplasms exhibited sedimentation coefficients of 3.5 to 4.0 S on sucrose gradients of either low or high ionic strength. From Scatchard analyses of titration data, apparent dissociation constants of 4 to 6 X 10(-8) M were determined for ligand-binding protein complexes from either tumor. Specific progesterone-binding capacities varied considerably, ranging from 150 to 650 fmoles/mg of cytosol protein. Optimal binding of [3H]progesterone was reached by 2 to 3 hr at 3 degrees, pH 7.4, and then decreased rapidly. Specificity studies indicated that cortisol, corticosterone, and triamcinolone acetonide competed effectively for [3H]progesterone-binding. This suggested that [3H] progesterone was bound largely to a macromolecule distinct from transcortin, which does not bind glucocorticoids containing 9alpha-fluoro groups. Aldosterone, as well as several androgens and estrogens, were weak competitors of binding except at high concentrations. The nature of the inhibition of progesterone-binding sites by triamcinolone acetonide and corticosterone was competitive. Concurrent titrations of [3H]progesterone and [3H]triamcinolone acetonide-binding sites demonstrated that their binding capacities were similar, considering the relative stabilities of the complexes. These results, which indicated that progesterone and glucocorticoids compete for the same binding site, suggest that these hormones may influence mammary gland differentiation and development by a common mechanism.
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PMID:Characteristics of progesterone-binding components in neoplastic mammary tissues of the rat. 17 35

A total 39 kidney tumors were induced by a continuous oral administration of N-butylnitrosourea (BNU) in 33 out of 204 rats of W/Fu strain and of 41 (W/Fu X ACI/N)F1 rats. No spontaneous renal tumors were observed among 66 males and 109 females of W/Fu rats which survived beyond the age of 19 months. Histologically, renal cell and mesenchymal types were commonly observed; 24 cases belonging to the former and 11 cases to the latter. Two cases of nephroblastoma were also encountered. There was no sex difference in renal tumorigenesis with BNU as a whole. Castration in both sexes was apparently inhibitory for kidney tumor development. Estrogenization of castrated rats either by syngeneic ovary graft or by repeated injections of estradiol benzoate enhanced tumor induction with BNU. Progesterone was not effective in restoring the tumor incidence in castrated rats. Distribution of histological types of tumors thus induced differed among the hosts with different hormonal conditions; in males the majority was renal cell type, whereas almost all mesenchymal tumor and nephroblastoma cases were found in intact females or estrogenized rats. BNU induced a variety of tumors in several organs including cerebral hemisphere, peripheral nerves, mammary glands, hematopoietic system, digestive tracts, and so on. However, such concurrence did not affect the development of renal tumors in the present study.
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PMID:Influence of sex hormones on kidney tumors induced in rats with N-butylnitrosourea. 17 65

Six patients who took oral contraceptive agents for 5 to 18 years developed endometrial neoplasia. Endometrial adenocarcinoma occurred in 4 of these patients and severe adenomatous hyperplasia occured in 2. Five of the 6 patients took sequential agents; 1 patient used a combined agent. An additional patient who took Premarin and Provera sequentially developed adenocarcinoma of the endometrium. Eighteen cases of endometrial adenocarcinoma and 7 cases of adenomatous hyperplasia in patients with long-term sequential oral contraceptive use have previously been reported by others. Progestogens may not be completely protective against the endometrial cancer-causing potential of the estrogens, especially in the sequential regimens.
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PMID:Endometrial carcinoma and oral contraceptive agents. 19 73

At the Wilford Hall U.S. Air Force Base Medical Center, Texas, about 4000 postmenopausal women received estrogen replacement therapy during 1975. Of these, 2700 took estrogens only and 1240 were given a progestogen along with estrogen. Hysterectomy had been done previously on 1700 patients (42%), leaving 2300 with intact uteri and a risk of endometrial cancer. Adenocarcinoma of the endometrium was diagnosed in 7 patients. Of these, 6 had received estrogen therapy. There was 1 endometrial malignancy in a patient also receiving a progestogen. Among 510 untreated postmenopausal women with intact uteri, 1 adenocarcinoma of the endometrium was found. Type and dosage of estrogen were unrelated to endometrial malignancy. In addition to the 7 endometrial cancers from the clinic, 22 cases were diagnosed elsewhere and referred for treatment, 11 of these had received no hormones. 10 were taking estrogens and 1 was receiving Oracon for birth control. The incidence of endometrial malignancy in the U.S. is reported to be 21/100,000 women/year. There is a 3-fold to 9-fold increased risk of endometrial cancer associated with obesity alone. The probability that untreated postmenopausal women with intact uteri will develop carcinoma of the endometrium is 1/1000/year. With estrogen users, it is reported to be increased -7.6/1000 women/year. In the author's clinic during 1975, the incidence among those receiving only estrogen was 4.7/1000. Among those also receiving a progestogen the incidence was .8/1000. Unopposed estrogens apparently have a role in the etiology of endometria hyperplasia and neoplasia through incomplete shedding of the endometrium. Progesterone produces more complete sloughing of the endometrium and also converts all degrees of hyperplasia into secretory endometrium. Nulliparity, infertility, and anovulation are predisoposing factors to endometrial carcinoma. Progestogens are palliative therapy for endometrial cancer.
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PMID:Estrogens, progestogens and endometrial cancer. 19 79

Kinetic and molecular properties of components binding [3H]triamcinolone acetonide were studied using 105,000g supernatants of lactating mammary gland, R3230AC, and dimethylbenz[a]anthracene (DMBA) induced mammary tumors of the rat. Using a dextran-coated charcoal adsorption procedure, the relationship between specific glucocorticoid binding and protein concentration was linear in the range of 0.5-4.0 mg/reaction. These cytoplasmic macromolecules bound [3H]triamcinolone acetonide with limited capacity (50-400 fmol/mg of cytosol protein) and high affinity, Kd approximately 10(-8)-10(-9) M. Optimal binding was obtained when homogenizations were made in Tris buffers, at pH 7.4, containing monothioglycerol. Time course of association of [3H]triamcinolone acetonide and its binding sites showed maximal binding by 6-8 hr at 3 degrees which remained unchanged up to 24 hr. The rate constant of association at 3 degrees was in the range of 2-4 x 10(5) M-1 min-1. The rate constant of dissociation of bound [3H]triamcinolone acetonide could not be calculated accurately since the reaction was essentially irreversible for 5 hr at 3 degrees. Estimation of the half-life of the steroid-binding protein complexes from the Kd and the rate constant for association gave a value of 11-12 hr. From ligand specificity studies, the glucocorticoids, triamcinolone acetonide, corticosterone, cortisol, and dexamethasone competed well for [3H]triamcinolone acetonide binding sites. Progesterone, aldosterone, and the anti-glucocorticoid, cortexolone, were also good competitors while androgens and estrogens were weak inhibitors of binding. The binding compenents sedimented at 7-8 S in sucrose gradients of low ionic strength and dissociated into lower molecular weight components sedimenting at 4-5S in high ionic strength gradients. Studies in vivo using animals bearing the DMBA-induced tumor demonstrated that [3H]triamcinolone acetonide binding complexes were present in cytoplasmic and nuclear compartments. Sedimentation coefficients of the cytoplasmic and nuclear forms of these receptors labeled in vivo were 7-8S and 4-5S, respectively. These studies suggest that the molecular and kinetic binding properties of glucocorticoid receptors in neoplastic mammary tissues are similar to those of the normal mammary gland.
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PMID:Comparison of glucocorticoid-binding proteins in normal and neoplastic mammary tissues of the rat. 23 78

Drug toxicity testing is required by the U.S. Food and Drug Administration in bitches of beagle dogs for 7 years and in female rhesus monkeys for 10 years at 25-50 times the human dosage. Progesterone, medroxyprogesterone acetate, megesterol acetate, chlormadinone acetate, chloroethynl norethisterone and chloroethynyl norgestrel are some compounds which have induced tumors in beagle dogs. However, the endocrinology of the beagles is unlike that of a woman and binding affinity of synthetic progestogens to breast cytoplasmic progesterone receptors of the beagle and women have striking differences. Some progestogen compounds which do not produce neoplasia in dogs because of too low a dose are most potent in women. Both the WHO and the Committee on Safety of Medicines concluded that progestogen-induced breast tumors in beagles are unhelpful in predicting possible breast cancer in women who use oral contraceptives.
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PMID:Hounding the pill. 31 66

Nine ovarian Sertoli-Leydig tumors, showing varying degrees of differentiation, one pure ovarian Sertoli cell tumor, and one poorly differentiated stromal tumor of the testis, were examined for the presence of testosterone, estradiol and progesterone with an indirect immunoperoxidase method on formalin fixed paraffin embedded tissue. Clinically all nine patients with Sertoli-Leydig tumors had evidence of increased androgen production, manifested by either hirsutism or virilization; elevated serum testosterone was found in all four patients in whom it was measured. The patients with the pure ovarian Sertoli cell and testicular tumors were asymptomatic except for the presence of a mass. Testosterone was identified in Leydig cells in nine instances, in Sertoli cells in six, and in poorly differentiated spindle cells resembling the mesenchyme of the embryonic gonad in two. Cells with vacuolated cytoplasm, both Sertoli and Leydig cells, though positive for lipid were consistently negative for testosterone. Estradiol was present in Leydig cells in nine instances, in Sertoli cells in five, and in primitive gonadal stomal cells in two. The pattern of distribution was similar to that of testosterone but the intensity of the reaction for estradiol was generally less than that for testosterone. Progesterone was identified in Sertoli cells in one instance and was weakly positive in Leydig cells in three instances. The presence of testosterone and estradiol in both Sertoli and Leydig cells as well as in primitive spindle cells resembling those found in the embryonic gonad suggests that the latter cell is the precursor for both Sertoli and Leydig cells.
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PMID:An immunohistological study of steroid localization in Sertoli-Leydig tumors of the ovary and testis. 36 Dec 11


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