Divergent changes in murine pituitary concentration of free alpha- and thyrotropin beta-subunits in hypothyroidism and after thyroxine administration.
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Biomedical subjects
Publications and source records attributed to D S Ross.
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We have previously demonstrated divergent changes in pituitary free TSH beta and alpha-subunit concentrations in hypothyroid mice during prolongation of experimental hypothyroidism and after T4 administration. This report compares the simultaneous responses of pituitary and thyrotropic tumor TSH, TSH beta, and alpha-subunit to 12 days of T4 administration in four groups of hypothyroid LAF1 mice bearing thyrotropic tumors. Half of each group received daily injections of T4 (10 micrograms/100 g BW, ip) for 12 days; the other half of each group received saline. Plasma concentrations of TSH, free TSH beta, and free alpha-subunit were suppressed by T4 administration to 0.1-1.5%, 2.0-3.9%, and 4.1-25% of control concentrations, respectively. Pituitary TSH and free TSH beta concentrations fell significantly with treatment to 24-43% and 10-28% of control concentrations, respectively. In contrast, pituitary alpha-subunit concentrations did not fall (they were 106-203% of control values), and a rise in the pituitary alpha-subunit concentration was statistically significant in one group (P less than 0.02). Thyrotropic tumor TSH and free TSH beta concentrations fell significantly with treatment to 9-31% and 8-35% of control concentrations, respectively. Tumor alpha-subunit concentrations did not fall (they were 87-195% of control values), and a 2-fold rise was statistically significant in one group (P less than 0.05). Both pituitary and tumor alpha-subunit to TSH beta molar ratios increased significantly with T4 administration in all groups. We conclude that (1) pituitary and thyrotropic tumor TSH beta concentrations fall after 12 days of T4 administration while alpha-subunit concentrations are unchanged or actually rise; (2) this divergent response is qualitatively similar in hypothyroid mouse pituitary and thyrotropic tumors; and (3) these data suggest differences between the regulation of intracellular TSH beta and alpha-subunit.
This report describes the conversion of a murine pituitary thyrotropic tumor (MGH 101) to a pure alpha-subunit-secreting tumor (MGH 101A) during a 6-yr period of serial transplantation. MGH 101 was a thyrotropic tumor originating from a hypothyroid mouse pituitary, growing only in hypothyroid hosts, and secreting large quantities of intact TSH and free alpha-subunit. Between the fourth and ninth transplantation generations, tumor TSH secretion declined progressively by at least 500-fold, to undetectable levels. In contrast, tumor secretion of free alpha-subunit decreased only 10-fold, and has since remained stable for nine transplantation generations. During the conversion to pure alpha-subunit secretion, MGH 101A exhibited growth in euthyroid as well as hypothyroid hosts, and increased its growth rate 2 to 3-fold. In contrast, the conventional thyrotropic tumor TtT 97 has maintained its secretion of both intact TSH and free alpha-subunit, its dependence on a hypothyroid environment, and its slower growth rate for nine generations. Gel chromatography of the media from tumor cell cultures confirmed that MGH 101A secreted only the free alpha-subunit, whereas TtT 97 secreted immunoactive TSH, TSH beta, and free alpha-subunit which eluted as separate peaks. We conclude that a dependent thyrotropic tumor has spontaneously developed into a pure alpha-subunit-secreting tumor which is independent of host thyroid function for its growth and alpha-subunit production.
One hundred and nineteen patients with Graves' hyperthyroidism who were treated with 131I alone or 131I followed by potassium iodide (131I + KI) were studied retrospectively. Patients in both groups who required only a single dose of 131I for successful treatment of hyperthyroidism had similar age, gland size, 24-h radioactive iodine uptake, pretreatment serum T4 concentrations, and radioactive iodine treatment dose. Seven weeks after 131I, mean serum T4 concentrations were 12.3 +/- 6.1 micrograms/dl (mean +/- SD) in patients who received 131I alone and 8.0 +/- 3.9 micrograms/dl in patients who received 131I + KI (p less than 0.001). Sixty percent of the patients who received 131I + KI and remained euthyroid 1 yr after 131I treatment developed documented transient hypothyroidism while receiving KI (serum T4, 1.4 +/- 0.9 micrograms/dl). Patients with transient hypothyroidism receiving KI had larger estimated thyroid gland weights when hypothyroid than patients whose hypothyroidism was permanent (32 +/- 6 vs. 16 +/- 11 g; P less than 0.001). The overall incidence of hypothyroidism 1 yr after treatment with 131I was 58% in each of the two groups. Sixteen percent of each group were not successfully treated by a single dose of 131I and required further therapy. Adjunctive KI effectively treated thyrotoxicosis more rapidly than 131I alone without adversely affecting outcome at 1 yr; however, patients taking KI more often develop transient hypothyroidism.
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Inbred male WF rats were given im injections of one of two antigenically and histologically distinct syngeneic tumor isografts, adenocarcinoma DMH-W 163 or spontaneous renal cell carcinoma SPK. Serum and peripheral blood lymphocytes were harvested from tumor-bearing and normal age-matched controls before and after isograft challenge at weekly intervals. Serial circulating immune complex (CIC) levels were quantitated by polyethylene glycol (PEG) insolubilization. T-cell mitogen responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were followed serially. Tumor growth was measured at least weekly. PEG-CIC values rose early after tumor injection, increased with tumor growth, and declined in some animals just before death. Mitogen response to PHA was significantly decreased in isografted tumor-bearing rats, particularly at later stages of tumor development, compared to normal uninoculated controls. Responses to Con A were variable, and suppression was not always seen in tumor bearers. In animals that did not have progressive tumor growth after isograft injection, PEG-CIC levels did not change and responses to PHA were not suppressed. Patterns of CIC change and responses to PHA were not affected by differences in tumor histology or growth rates. Thus serial CIC levels measured by the PEG assay correlate with tumor growth and precede nonspecific suppression of T-cell mitogenic response in these animal tumor models.
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The antithetical relationship of the F and V alleles in British Friesian cattle was found to be imperfect. The presence of another allele was inferred. It was suspected of being native to the British Isles. Parentage records that contravened the assumption that F + V -- and F--V + animals were homozygous were not necessarily erroneous. Black and white cattle in the Netherlands have received semen from a bull carrying the allele.
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A study was made of the progeny of a pair of dizygotic twin bulls whose blood group phenotypes were identical but were genotypically different, indicating a complete replacement of one of the bulls haematopoietic tissus by that of its cotwin. The study was made in an attempt to determine whether the genes of one sibling were transmitted by the other. It it were so it would follow that the germ cells of the testes were chimaeric. Blood typing of 97 progeny provided no evidence to indicate the presence of such a germ cell chimaerism.
Chest radiographs of 661 British electric-arc welders have been examined by three film readers experienced in the radiology of pneumoconiosis. About 7% of the welders showed signs of small rounded opacities of category 0/1 or greater. No definite evidence of large opacities (Progressive Massive Fibrosis) was seen. The prevalence of chest abnormalities other than pneumoconiosis was 7%. A clear association between prevalence of small rounded opacities of category 0/1 or greater and years of exposure to fumes was established, although few signs of severe grades of simple pneumoconiosis were seen.
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