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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Choleragen stimulates steroid secretion and adenylate cyclase in three cell lines, adrenal tumor line (Y-1), a corticotropin-resistant mutant derived from Y-1 called OS-3, and a receptor-deficient Leydig tumor line (I-10). Sensitivity for half-maximal stimulation varies from 3 to 36 pM choleragen, the I-10 line being the most sensitive. Latency before the onset of steroidogenesis is longer in OS-3 and I-10 cells than in the Y-1 line. In both OS-3 and I-10 cells choleragen stimulates adenylate cyclase whether ITP or 5'-guanylylimidodiphosphate is the regulatory cofactor used. In addition to the responses of the receptor-deficient lines, choleragen does not, during its latency, block the response to corticotropin in Y-1 cells; corticotropin does not block binding of 125I-labeled choleragen to Y-1 cells; gangliosides do not interfere with the corticotropin-induced stimulation of Y-1 cells. We conclude that the corticotropin and choleragen receptors are different.
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PMID:Choleragen stimulates steroidogenesis and adenylate cyclase in cells lacking functional hormone receptors. 17 54

Lipopolysaccharides (endotoxins) from Escherichia coli, Serratia marcesens and Salmonella typhosa stimulated steroid production in Y-1 adrenal tumor cells in culture with a latent period of 3-4 h. Lipid A, derived from Escherichia coli lipopolysaccharide, also stimulated steroidogenesis. Lipopolysaccharides and lipid A also stimulate adenylate cyclase activity and cause rounding of the cells. In contrast, lipopolysaccharides do not stimulate steroidogenesis in receptor-deficient adrenal tumor cells (OS-3) or Leydig tumor cells (I-10). This tends to rule out contamination by enterotoxin to which these lines respond. Although both hormone and lipopolysaccharide responses are lost in these lines, there was no interaction between these sites as judged by the failure of lipopolysaccharides to block, during their latency, the response to corticotropin in Y-1 cells. The possibility that the lipopolysaccharide effect is one on membrane conformation is discussed.
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PMID:Endotoxic lipopolysaccharides stimulate steroidogenesis and adenylate cyclase in adrenal tumor cells. 17 55

In the adrenal tumor cell system ganglioside Gm1 inhibited cholera enterotoxin (CT)-induced steroidogenesis if it was preincubated with the toxin or added to adrenal cells 10 min before CT. In the preincubation studies a molar ratio of Gm1 to toxin of 3:1 was necessary for half-maximal inhibition of steroidogenesis. On the other hand, horse serum anticholeragenoid neutralized the steroidogenic response to cell-bound CT by 50% if it was added to adrenal monolayer cultures 15 min after the toxin. Specific antiserum was able to neutralized 20% of the toxin-induced activity even if it was added to adrenal cultures 2 h after CT. Phase contrast microscopy demonstrated that partial neutralization of the biochemical effect of CT by horse serum anticholeragenoid was accompanied by partial prevention of toxin-induced rounding of adrenal cells. Further studies showed that pretreatment of cultured adrenal cells with a maximal dose of CT increased cyclic adenosine 3'-5'-monophosphate formation in response to a maximal stimulating dose of adrenocorticotropin. This result suggested potentiation of hormonal activation of adenylate cyclase in intact adrenal tumor cells in response to CT.
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PMID:Interaction of cholera enterotoxin with cultured adrenal tumor cells. 17 45

Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action.
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PMID:Regulation of thyrotropin (TSH) release and production in monolayer cultures of transplantable TSH-producing mouse tumors. 17 85

Data from cultured cells have suggested that cyclic AMP and cyclic GMP may be important determinants of cell growth and transformation. However, few studies have examined cyclic nucleotide content and metabolism in naturally occurring tumors of man. Accordingly, in the present study we compared cAMP and cGMP levels and metabolism in carcinomas of the human colon to those of the adjacent uninvolved mucosa after therapeutic resection of these tissues. The cAMP content of the tumors, determined in samples frozen 30 min after excision, was significantly lower than that of the adjacent mucosa, when expressed on the basis of tissue wet weight, protein, or DNA content. By contrast, the cGMP content of the tumors was higher than that of the surrounding mucosa if calculated on the basis of tissue wet weight, but this difference did not persist when correction was made for the higher protein or DNA content of the tumors. Incubation of slices of mucosa or tumor with or without theophylline in vitro increased tissue cAMP and cGMP content above levels observed in frozen samples of the same tissue. However, after such incubations cAMP levels in the tumors remained clearly below that of the mucosa, while cGMP content of the two tissues did not differ. The failure of theophylline to abolish differences in cAMP content and the comparable activities of high and low Km cAMP-phosphodiesterase in homogenates of the two tissues suggested that the lower cAMP content of the tumors was a consequence of diminished cAMP synthesis rather than enhanced degradation. This possibility was supported by the reduction in basal and maximal prostaglandin E1 (PGE1)-responsive adenylate cyclase activity found in tumor homogenates relative to those of mucosa, and the lower levels of cAMP in tumor slices after incubation of the tissues with a maximal dose of PGE1 and theophylline. Since NaF-responsive adenylate cyclase activity was not significantly reduced in the tumors, the lower basal and PGE1 activities may not be related to a deficiency of the catalytic unit of the cyclase complex in this tissue. The role of reduced activity of the adenylate cyclase-cAMP system and/or reduced tissue cAMP-to-cGMP ratios in the pathogenesis of colonic carcinoma is uncertain, but these changes might favor unregulated cellular proliferation.
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PMID:The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon. 17 89

ACTH stimulated steroidogenesis and cAMP (adenosine 3',5'-monophosphate) accumulation in an adrenocortical mouse tumor cell line (clone Y1) with Kd values which differed by more than one order of magnitude (5.2 X 10(-11) M and 7 X 10(-10) M, respectively). All of the cAMP formed in response to added ACTH appeared extracellularly in 5- or 30-min incubations. ACTH, at 5 and 10 muU/ml, stimulated steroidogenesis to 25% and 40% of maximum activity; and increased the extracellular accumulation of cAMP 1.4-fold and 2.3-fold, respectively. The effects of ACTH appeared to be via an action on intracellular ATP, specific for cAMP and dependent on an ACTH-sensitive adenylate cyclase system. These observations indicate that ACTH increases cAMP accumulation in Y1 cells at virtually all steroidogenic concentrations and suggest that cAMP is an essential component of ACTH-stimulated steroidogenesis.
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PMID:Steroidogenesis and extracellular cAMP accumulation in adrenal tumor cell cultures. 17 21

Adenylate cyclase systems were examined in purified membrane preparations from normal rat liver and several Morris hepatomas with differing growth rates. All tumor membrane preparations had lower relative specific activities than did liver preparations. Liver adenylate cyclase was stimulated by fluoride, glucagon and guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Membranes from two slow-growing hepatomas (hepatomas 20 and 21) contained adenylate cyclase activities which are also stimulated by each of these three modulators. Membrane adenylate cyclases from several fast-growing hepatomas (hepatomas 3924A, 7777, 5123tc, and 9618A2) were marginally stimulated by glucagon but were readily stimulated by fluoride and Gpp(NH)p. Examination of the highly specific binding of 125I-glucagon to the various membrane preparations revealed much less binding in all the tumor membranes than in liver membranes. More detailed kinetic examination of membranes prepared from liver, slow-growing hepatoma 21 (which had reasonable binding to and stimulation by glucagon), and fast-growing hepatoma 3924A (which had marginal binding to and stimulation by glucagon) revealed major differences in rates of cyclic adenosine 3':5'-monophosphate production in the absence and presence of glucagon, Gpp(NH)p, and glucagon plus Gpp(NH)p and in the combined alteration of magnesium:adenosine 5'-triphosphate ratio and temperatures. The different kinetic characteristics in the hepatoma adenylate cyclase systems may be due to different structural characteristics of the tumor membranes or may be due to altered hormonal receptors, catalytic units, or receptor-catalytic unit interrelationships within the tumor membrane.
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PMID:Regulation of the adenylate cyclase system in transplantable hepatomas. 17 31

Isoproterenol, corticotropin (ACTH), and triodothyronine immobilized on glass and Sepharose beads by diazotization procedures have been shown to interact with cultured tumor cells of "target tissue" origin. Cells used were rat glioma cells (C6), rat adrenal tumor cells (Y-1), and rat pituitary tumor cells (GH3). The rat glioma cells bound principally to immobilized isoproterenol, whereas the rat adrenal tumor cells bound to immobilized corticotropin, and rat pituitary tumor cells bound to immobilized triiodothyronine. Binding was inhibited by preincubation of the cells in soluble drug or hormone. With C6 cells there was a positive correlation between adenylate cyclase [ATP pyrophosphate-lyase (cyclizing, EC 4.6.1.1] stimulation and the degree of binding to the immobilized isoproterenol. Norepinephrine, bound through the ethanolamine side chain via an amide linkage, did not bind cells, demonstrating specific structural requirements for drug-cell interactions. HeLa cells were shown to bind tightly to diphtheria toxin coupled to Sepharose beads via an amide bond. This binding was inhibited by prior incubation of the Sepharose toxin with purified antitoxin. Toxin bound to Sepharose via an azo bond did not bind cells. These data suggest that the cell affinities are due to cell surface receptors interacting with the immobilized drugs and hormones, and that the observed affinities possibly reflect the relative receptor complement of these cells.
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PMID:Affinity isolation of cultured tumor cells by means of drugs and hormones covalently bound to glass and Sepharose beads. 18 May 34

Experiments in vitro on tissue from a feminizing adrenocortical carcinoma removed from a postmenopausal patient are described. Portions of the adrenal tumor were cultured. The effects of ACTH, prolactin, and other protein hormones on the synthesis and secretion of steroid hormones by the cultured tissue were studied. Steroids were extracted from the culture medium with ethyl acetate. Steroid production was determined by high resolution-mass fragmentography and by radioimmunoassay. Results suggest that in vitro neither growth hormone (GH) nor luteinizing hormone (LH), at the concentrations used, effectively stimulated the synthesis and secretion of estradiol-17beta by the adrenal tumor tissue. However, ACTH and prolactin with insulin, appearing to influence the action of both these hormones, stimulated the output of estradiol-17beta. Steroid was being synthesized during the 3-day culture period. The tumor tissue actively synthesized and secreted into the medium estrone as well as estradiol-17beta under the influence of ACTH and prolactin with insulin. Data also suggest that LH and GH were capable of influencing the synthesis and secretion of androstenedione by the tissue explants. No DNA sulphate was present in the media from the tumor tissue cultures before or after incubation with either ACTH or prolactin. Results from studies with normal adrenal tissue in culture indicated that DNA sulphate, DHA, and androstenedione were present in the culture medium after 3 days' incubation. In this report the concentration of endogenous estrone relative to estradiol-17beta and estradiol was found to be high. The effect of protein hormones, other than ACTH, on adenylate cyclase activity of this tumor tissue indicated a lack of specificity of the membrane receptor sites. High resolution-mass fragmentography had greater specificity than radioimmunoassay.
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PMID:In vitro synthesis of steroids by a feminising adrenocortical carcinoma: effect of prolactin and other protein hormones. 18 Jul 40

The effects of prostaglandins on adenylate cyclase activity have been examined in membranes purified from normal rat liver and from a series of Morris hepatomas. Prostaglandin E1 gave the greatest stimulation (up to two-fold) in all membranes. However, prostaglandins A1, A2, and F2alpha, although stimulatory in liver and four tumor membranes, were inhibitory of adenylate cyclase activity in membranes from two of the fast-growing tumors. Arrhenius plots yielded broken line curves (at 20 degrees C) for the basal activity of all enzymes. Addition of various prostaglandins caused shifts in the broken line curves and/or produced nonbroken (straight) line curves for the liver and many of the hepatoma adenylate cyclases.
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PMID:Effect of prostaglandins on adenylate cyclase activities in membranes from liver and transplantable hepatomas. 18 16


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