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

Pituitary null cell adenomas and oncocytomas are tumors not associated with clinical or biochemical evidence of hormone excess; morphological studies have not hitherto revealed their origin or the nature of their hormone production, if any. We examined the in vitro secretory activity of seven null cell adenomas and five oncocytomas which caused symptoms of a mass lesion and variable degrees of hypopituitarism. All tumors were classified at the time of surgical resection using immunohistochemistry and electron microscopy. RIA revealed the presence of FSH, LH, and alpha-subunit of pituitary glycoprotein hormones in the culture medium of eight tumors, FSH and alpha-subunit in the medium of one tumor, and TSH, FSH, LH, and alpha-subunit in the medium of three adenomas. Morphological examination of cultured tissues confirmed the presence of tumor resembling those in the initial surgical specimen. Thus, we conclude that null cell adenomas and oncocytomas contain cells that can produce pituitary glycoprotein hormones, and that the majority produce gonadotropins.
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PMID:Gonadotropin secretion in vitro by human pituitary null cell adenomas and oncocytomas. 242 Aug 15

To determine whether sulfate and/or sialic acid are present on secreted mouse TSH, thyrotropic tumor minces and hypothyroid pituitaries were incubated with [3H]methionine and [35S]sulfate, or [35S]methionine and [3H]N-acetylmannosamine. The metabolically labeled TSH and free alpha-subunits were then analyzed by gel electrophoresis. [3H]N-Acetylmannosamine was a specific precursor (greater than 80%) for the sialic acid [3H]N-acetylneuraminic acid, as established by HPLC characterization of tritium label released by acid hydrolysis. Each of the three secreted subunits (TSH alpha, TSH beta, and free alpha) incorporated both sulfate and sialic acid. The incorporation of these labels was confirmed by the release of [35S]sulfate by endoglycosidase F and of [3H]N-acetylneuraminic acid by neuraminidase. Differential labeling of newly synthesized secreted TSH subunits was observed. In secreted TSH dimer, TSH beta incorporated 1.3 times more [35S]sulfate (P less than 0.05) and 2.5 times more [3H] N-acetylmannosamine (P less than 0.02) per carbohydrate chain than did TSH alpha. Secreted free alpha-subunit incorporated more [3H]N-acetylmannosamine, but less [35S]sulfate, then did secreted TSH alpha. To investigate the effect of TRH on TSH sulfation and sialylation, thyrotropic tumor minces and hypothyroid pituitaries were incubated with [35S]sulfate or [3H]N-acetylmannosamine, with or without 10(-7) M TRH; labeling was then normalized in each case to incorporation of [3H]mannose, a marker of the inner core sugars. TSH secreted in the presence of TRH had a lower sulfate to mannose ratio [28 +/- (+/- SE) 4% of control; P less than 0.05] and a lower sialic acid to mannose ratio (63 +/- 8% of control; P less than 0.05). TSH alpha and TSH beta were affected equally. No change was seen in the labeling of non-TSH secretory proteins. Differential glycoprotein sulfation and sialylation may, in part, explain the previously observed variability in isoelectric point, bioactivity, and MCR of TSH in different physiological states and may represent a point of regulation by TRH.
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PMID:Differential sulfation and sialylation of secreted mouse thyrotropin (TSH) subunits: regulation by TSH-releasing hormone. 242 82

Using specific radioimmunoassays, serum prolactin, TSH, LH, FSH, and inhibin levels were estimated in normal subjects and in patients with benign prostatic hyperplasia (BPH) before and after tumor resection. In the case of BPH, there was a significant rise in inhibin levels as compared to age-matched control groups, whereas LH and FSH levels were decreased significantly. The levels of inhibin and prolactin were significantly reduced after surgery, but no consistent changes in LH, FSH, or TSH levels were noted. The changes observed in hormonal levels in the BPH patients were not related to patient's age or size of the tumor.
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PMID:Circulating levels of inhibin, prolactin, TSH, LH, and FSH in benign prostatic hypertrophy before and after tumor resection. 243 3

Changes in serum growth hormone (GH) concentrations before and after TRH injection, oral glucose tolerance test (OGTT), L-dopa, CB-154 and LHRH administration were investigated in 78 gastric, 32 hepatocellular, 23 colonic, 20 pulmonary, 11 esophageal, 9 pancreatic and 9 other types of cancer patients. In addition, the effect of 5-FU or tegafur on thyroid function was studied in 39 gastric, 12 colonic, 8 hepatocellular, 5 pancreatic and 8 other types of cancer patients. The results obtained were as follows. 1) Paradoxical responses of growth hormones to TRH and OGTT were demonstrated in cancer patients, although normal increases in GH concentrations after L-dopa and CB-154 administration were shown. Incidences of GH response to TRH were significantly higher in female cancer patients than in male cancer patients, although there was no sex difference in the paradoxical responses of serum GH concentrations to OGTT. 2) After curative surgery, paradoxical responses of serum GH levels to TRH and OGTT were gradually diminished. Immunostaining of tumors using GH Ab was negative. Anti-tumor agents showed a stimulatory effect on the paradoxical response to OGTT. 4) More than 3 months after 5-FU or tegafur administration, significant elevations of serum T3, T4 and TBG concentrations were demonstrated in cancer patients, compared to pre-treatment values or those within 2 months after therapy, although there were no significant changes in serum thyroglobulin and TSH levels before and after therapy. In conclusion, tumor-dependent hypothalamic-pituitary changes were recognized in cancer patients. Long-term administration of 5-FU or tegafur caused elevations of serum T3 and T4 through high TBG concentrations.
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PMID:[Changes in endocrine status in cancer patients and the effect of chemotherapy on endocrine functions]. 243 76

Human chorionic gonadotropin (HCG) is a 40,000 dalton glycoprotein composed of two non-identical alpha- and beta-subunits. HCG and other related pituitary hormones, such as human luteinizing hormones (HLH), human follicle stimulating hormone (HFSH), and human thyroid stimulating hormone (HTSH), consist of nearly identical alpha-chains. However, their beta-chains show a variable degree of amino acid sequence homology. Detection and subsequent quantitative determination of HCG in human biological fluids is useful in early diagnosis of pregnancy and in monitoring of tumor patients. For these applications monoclonal antibodies (McAbs) with defined specificity are required. Several hybridomas secreting McAbs to HCG have been isolated. The hybridoma cells have been developed by fusion of NS1 myeloma cells with spleen cells of Balb/C mice immunized with HCG. With the aid of an enzyme linked immunosorbent assay, six McAbs were characterized. McAbs A-73, A-76 and A-112 recognize an epitope present on the alpha-HCG subunit. McAbs B-68, B-69 and B-106 recognize an antigenic determinant associated with the beta-HCG subunit. Two of these McAbs: B-68 and B-69 are directed against an epitope on the B subunit specific to the HCG molecule and B-106 McAb towards an epitope common to HCG, TSH, LH and FSH molecule. In a hemagglutination test, only the A-73 McAb is capable of inducing agglutination of sheep red blood cells coated with HCG, thus suggesting that this McAb recognizes a repeating epitope on the alpha-HCG molecule.
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PMID:Development of monoclonal antibodies directed against different epitopes of human chorionic gonadotropin. 243 77

Dexamethasone, like T3, inhibits the production of TSH. T3 inhibits TSH synthesis by reducing transcription of the genes encoding TSH-beta and alpha-subunits. Little information is available concerning the effects of dexamethasone on the individual subunits, or the combined effects of dexamethasone with T3. In a preliminary study, hypothyroid mice bearing the thyrotropic tumor TtT 97 were treated with 25, 250, or 500 micrograms dexamethasone ip daily for ten days. Plasma levels of TSH and its subunits were unchanged after 25 micrograms of dexamethasone and maximally suppressed after 250 micrograms. Plasma TSH was reduced to 51% (P less than .02), free TSH-beta to 54% (P less than .01), and alpha-subunit to 62% (P less than .001) of control values. In two similar experiments hypothyroid mice bearing TtT 97 were treated with dexamethasone (250 micrograms), T3 (0.5 or 1 microgram), or both dexamethasone with T3 for 10 days. Total alpha-subunit and TSH-beta were calculated by adding 1/2 TSH + free subunit concentrations. In the experiment using 1 microgram of T3, total plasma alpha-subunit was reduced by dexamethasone to 72%, by T3 to 45% (P less than .02), and by combined treatment to 23% (P less than .01) of control values. In the experiment using 0.5 microgram of T3, total plasma alpha-subunit was reduced by dexamethasone to 66% (P less than .05), by T3 to 67% (P less than .05), and by combined treatment to 46% (P less than .02) of control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of changes in plasma thyrotropin beta- and alpha-subunits, and mouse thyrotropic tumor thyrotropin beta- and alpha-subunit mRNA concentrations after in vivo dexamethasone or T3 administration. 243 70

The expression of the microsomal (M) antigen on the surface and in the cytoplasm of a strain of rat thyroid cells (FRTL-5) is under the regulation of TSH. In the present report the mechanism by which TSH induces such expression was investigated with the use of human microsomal antibody-positive serum and an indirect immunofluorescence technique. Studies were also performed to ascertain whether the M antigen of FRTL-5 cells could be identified with thyroid peroxidase (TPO), as suggested by recent data obtained in human thyroid tissue. Preabsorption experiments showed that, like solubilized human thyroid microsomes, purified human TPO completely abolished the binding of microsomal antibody to FRTL-5 cells. No inhibition was obtained by preabsorption with control human tissues (placenta, liver, and spleen) or human thyroglobulin, indicating that the antigen recognized by microsomal antibody in FRTL-5 cells was TPO. After 72 h of TSH withdrawal from the culture medium the M/TPO antigen disappeared from the surface and the cytoplasm of FRTL-5 cells. Readdition of TSH (250 microU/ml) to the culture medium of cells lacking the M/TPO antigen elicited its reappearance within 24-48 h. This effect of TSH was prevented by 10 microM cycloheximide or 0.5-5 micrograms/ml actinomycin D. Two well known stimulators of the adenylate cyclase-cAMP system, cholera toxin and forskolin, mimicked TSH in inducing the reappearance of the M/TPO antigen. A similar effect was observed with use of the phosphodiesterase inhibitor isobutylmethylxanthine. Reappearance of M/TPO antigen was also produced by the cAMP analog 8-bromo-cAMP. The tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate, which stimulates thyroid cell growth through a cAMP-independent pathway, was ineffective in inducing the M/TPO antigen in FRTL-5 cells. The present data indicate that 1) thyroid peroxidase accounts for most, if not all, of the microsomal antigen of FRTL-5 cells; and 2) TSH modulates the expression of the M/TPO antigen in FRTL-5 cells by a mechanism that involves cAMP production and requires mRNA formation and subsequent protein synthesis.
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PMID:Studies on the mechanism responsible for thyrotropin-induced expression of microsomal/peroxidase antigen in FRTL-5 cells. 245

We have determined the structures of high mannose (Man) oligosaccharide units at individual glycosylation sites of mouse TSH. Mouse thyrotropic tumor tissue was incubated with D-[2-3H]Man with or without [14C]tyrosine ([14C] Tyr) for 2, 3, or 6 h, and for a 3-h pulse followed by a 2-h chase. TSH heterodimers or free alpha-subunits were obtained from homogenates using specific antisera. After reduction and alkylation, subunits were treated with trypsin. The tryptic fragments were then loaded on a reverse phase HPLC column to separate tryptic fragments bearing labeled oligosaccharides. The N-linked oligosaccharides were released with endoglycosidase-H and analyzed by paper chromatography. Man9GlcNac2 and Man8GlcNac2 units predominated at each time point and at each specific glycosylation site, but the processing of high Man oligosaccharides differed at each glycosylation site. The processing at Asn23 of TSH beta-subunits was slower than that at Asn56 or Asn82 of alpha-subunits. The processing at Asn82 was slightly faster than that at Asn56 for both alpha-subunits of TSH heterodimers and free alpha-subunits. The present study demonstrates that the early processing of oligosaccharides differs at the individual glycosylation sites of TSH and free alpha-subunits, perhaps because of local conformational differences.
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PMID:Rates of processing of the high mannose oligosaccharide units at the three glycosylation sites of mouse thyrotropin and the two sites of free alpha-subunits. 245 13

We have studied the differential susceptibility to N-glycanase (peptide-N4-[N-acetyl-beta-glucosaminyl]asparagine amidase) of oligosaccharides at the individual glycosylation sites of mouse TSH and free alpha-subunits. Mouse thyrotropic tumor tissue or hypothyroid pituitary tissue were incubated with D-[2-3H]mannose for 6 h. [3H]Mannose-labeled TSH or free alpha-subunits were obtained from homogenates using specific antisera and were digested with N-glycanase in their native state or after heat denaturation and reduction in the absence or presence of detergents. Tryptic fragments of the digestion products were then analyzed by reverse phase HPLC so that the effects of N-glycanase at the individual glycosylation sites could be determined. N-Glycanase treatment of native molecules did not cleave oligosaccharides efficiently at Asn56 of alpha-subunits and Asn23 of TSH beta, whereas oligosaccharides at Asn82 of alpha-subunits were more susceptible regardless of whether the alpha-subunits were combined with TSH beta. Heat denaturation, reduction, and the presence of detergents did not substantially increase the cleavage by N-glycanase of the protected oligosaccharides, suggesting that the primary structures of the TSH subunits influenced efficiency at specific sites. Pretreatment of free alpha-subunits with trypsin failed to enable N-glycanase to work fully, as oligosaccharides at Asn56 were cleaved less effectively than those at Asn82. Thus, the susceptibility to N-glycanase differs at the individual glycosylation sites of mouse TSH and free alpha-subunits, and these differences may result from effects of the primary structures of the TSH subunits.
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PMID:Differential susceptibility to N-glycanase at the individual glycosylation sites of mouse thyrotropin and free alpha-subunits. 245 9

The immunohistological classification of 97 pituitary adenomas revealed in 34 cases alpha-subunit (a-su) positive cells in the tumor tissue. In 15 cases a-su was the only hormone found, in 11 cases the beta-subunits of the glycoprotein hormones could also be detected (10 cases with LH/FSH and 1 case with TSH). In 8 cases a-su was found simultaneously together with other hormones of the pituitary (ACTH and a-su in 1 case, GH and a-su in 4 cases, prolactin and a-su in 2 cases, prolactin, GH and a-su in 1 case). A-su could be demonstrated to be partly simultaneously produced together with these hormones in identical cells and secretory granules. Next to prolactin, the a-su was the second most frequently occurring hormone that could be detected immunohistologically in our material.
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PMID:Simultaneous production of the alpha-subunit of glycoprotein hormones and other hormones in pituitary adenomas. 246 68


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