Alteration in the transmission of TSH-message to thyroid target in a transplantable rat thyroid tumor.

Plasma membranes derived from a transplantable rat thyroid tumor (line 1-5G in Wollman's classification), which is unresponsive to thyrotropin (TSH) but is responsive to dibutyryl 3', 5' cAMP, have been evaluated to localize the defect. TSH binding in tumor plasma membrane is slightly lower than in normal rat thyroid membranes. No change in affinity, but simply a lower capacity was observed.

Rat thyroid phosphofructokinase. Comparison of the regulatory and molecular properties with those of rat muscle enzyme.

The kinetic and molecular properties of rat thyroid phosphofructokinase (specific activity 134 units/mg) were compared with those of rat muscle phosphofructokinase (specific activity 135 units/mg). Thyroid and muscle phosphofructokinase showed similar sedimentation patterns in sucrose density gradients; their affinity for DEAE-cellulose was similar but not identical. A comparison of the kinetic properties revealed differences in the pH optima.

Tetanus toxin interactions with the thyroid: decreased toxin binding to membranes from a thyroid tumor with a thyrotropin receptor defect and in vivo stimulation of thyroid function.

Normal rat thyroid membranes adsorb neurotoxicity when incubated with purified tetanus toxin. Membranes from a rat thyroid tumor with a thyrotropin receptor defect adsorb very little neurotoxicity when similarly evaluated. This inability of the tumor membranes to adsorb neurotoxicity is correlated with a defect in their ability to bind both 125I-labeled tetanus toxin and [125I]iodothyrotropin.

Effects of thyrotropin on the thyroid cell membrane: hyperpolarization induced by hormone-receptor interaction.

Cultured thyroid cells accumulate the lipophilic cation triphenylmethylphosphonium, indicating that there is an electrical potential (interior negative) across the plasma membrane. Thyrotropin stimulates the uptake of the lipophilic cation 3-fold, and the proton conductor carbonylcyanide-m-chlorophenylhydrazone causes efflux of triphenylmethylphosphonium accumulated in the presence or absence of thyrotropin. The stimulatory effect of thyrotropin on triphenylmethylphosphonium accumulation is not mimicked by human chorionic gonadotropin, a glycoprotein hormone with a similar structure whose target organ is not the thyroid, and the effect is abolished if the thyrotropin-receptor activity of the cells is destroyed by treatment with trypsin.

Phosphofructokinase (isozymes) activation by theophylline or by 3',5' cyclic AMP administration.

Phosphofructokinase activity of rat thyroid, kidney and muscle can be enhanced by in vivo administration of theophylline or cyclic AMP. This enhancement occurs in the different tissues to a different extent depending on the tissue-specific isozymes. Thyroid and muscle phosphofructokinase which is mainly A-type, is strongly stimulated after administering theophylline in the drinking water over a 8 days period.

Differences in phosphofructokinase regulation in normal and tumor rat thyroid cells.

The kinetic and molecular properties of a phosphofructokinase derived from a transplantable rat thyroid tumor lacking regulatory control on the glycolytic pathway were studied. The properties of the near-purified enzyme (specific activity 140 units/mg) were compared with those of phosphofructokinase from normal rat thyroid (specific activity 134 units/mg). The electrophoretic mobilities and gel elution behavior of these two enzymes were almost similar.

Diminished binding of thyroid-stimulating hormone in a transplantable rat thyroid tumor as a possible cause of hormone unresponsiveness.

The adenylate cyclase activity and the binding of 125I-labeled thyroid-stimulating hormone (TSH) of normal and tumor rat thyroid plasma membranes were compared. No significant difference in the basal and fluoride-sensitive adenylate cyclase activity between normal and tumor plasma membranes was observed. Thyroid plasma membranes responded to TSH, whereas the enzyme from the tumor plasma membranes was TSH insensitive.

[Presence of various protein kinases and of partially copurified endogenous substrates in the soluble fraction of an experimental tumor of the rat thyroid gland].

Various fractions containing protein-kinases have been partly purified from supernatant (105 000 g) of an experimental rat's thyroid cancer (1-8 Wollman). These fractions are activated at different levels by cyclic nucleotides and present an unequal affinity for protamine; they phosphorylate an endogenous substrate apparently copurified with the enzyme fractions and adorbed with them on calcium phosphate gel.

[Subcellular distribution of the protein kinase activity in the normal and neoplastic thyroid tissue of the rat].

Thyroid tissue has been fractionnated by centrifugation (105 000 q) of its homogenate. Protein-kinase activity in presence of histone is distributed in nuclei (11.5%) mitochondira (22.