INTERACTION OF THYROTROPHIN WITH THE HUMAN THYROTROPHIN RECEPTOR

Author:

SMITH B. REES,PYLE GWYNETH A.,PETERSEN V. B.,HALL R.

Abstract

The relationship between the binding of thyrotrophin (TSH) to receptors and the production of cyclic AMP has been investigated using crude human thyroid membranes. Receptor binding was studied by use of 125I-labelled bovine TSH, which had been purified by absorption to and elution from human thyroid membranes. This 125I-labelled material showed the same biological activity as the unlabelled hormone. Binding studies at equilibrium indicated that the association constant of the TSH–membrane interaction decreased as the amount of TSH bound increased. Kinetic data did not provide definite evidence that this was due to an effect of increasing receptor occupancy on the dissociation rate constant. Detectable stimulation by TSH of cyclic AMP production by the membranes was observed with as little as 30 μu. (1 ng) hormone. Increasing amounts of TSH over the range 0–250 μu. caused increases in the production of cyclic AMP, proportional to the amount of hormone bound. With larger amounts of TSH, increasingly greater amounts of bound hormone were required to give corresponding increases in cyclic AMP formation, and addition of TSH in amounts greater than 16 mu. resulted in progressive inhibition of cyclic AMP formation. Kinetic studies indicated that receptor binding was not rate-limiting in the stimulation of cyclic AMP production by TSH.

Publisher

Bioscientifica

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

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