Inhibition by adenosine of thyroidal T4 release in vitro.

Adenosine, like catecholamines, inhibits the thyroidal T4 release in vitro, when stimulated by TSH,N,O'-dibutyryl cyclic AMP [(Bu) 2cAMP], and phosphodiesterase inhibitors. Unlike catecholamines, the adenosine-induced inhibition is independent of adrenergic receptors. It is postulated that TSH stimulates thyroidal T4 release through a cAMP activated, adenosine-sensitive, protein kinase.

Inhibition of thyrotropin- and dibutyryl cyclic AMP-induced secretion of thyroxine and triiodothyronine by catecholamines.

Thyrotropin (TSH), 1 MU/ml and N6, O2'-dibutyryl adenosine 3',5-cyclic monophosphoric acid (dbcAMP) greatly enhanced the release of thyroxine (T4) and triiodothyronine (T3) from mouse thyroids incubated in vitro. L-Epinephrine (E) and L-norepinephrine (NE) strongly inhibited the TSH and dbcAMP-stimulated release of thyroid hormones; L-isoproterenol (IPNE) exerted a relatively weak inhibition. The inhibition by catecholamines was prevented by the alpha-adrenergic blocker, phentolamine; L-propranolol, a beta-adrenergic blocker, had no effect on the inhibition. The TSH-induced release of thyroid hormones was not affected by adrenergic blockers. Epinephrine did not affect the increase in thyroidal cAMP content induced by TSH. These results indicate that catecholamines act by way of an alpha-adrenergic receptor to suppress TSH-stimulated release of thyroid hormones at a point beyond cAMP formation.

An in vitro procedure for the estimation of thyroid hormone releasing factors in sera of thyrotoxic patients.

LATS containing sera and a number of Graves' disease sera stimulated T4 release from mouse thyroids in vitro as determined by RIA, thus confirming the presence of a thyroid hormone releasing factor in sera of thyrotoxic patients. The pattern of stimulation was similar to that previously shown for TSH in terms of T4 release time sequence. cAMP increase and catecholamine inhibition via alpha-adrenergic receptors. In the same in vitro system, neutralization with a human thyroid homogenate showed presence of LATS-Protector (LPA) in LATS negative thyrotoxic sera. The present study describes a simpler procedure for estimating LATS or similar activity, as compared to the McKenzie assay, and suggests identical receptor sites for TSH and other thyroid stimulators.

Thyroid uptake of 201thallium and its control by TSH.

Patients injected with 201Thallium (201Tl) for myocardial scanning present good thyroid visualization. Determinations in mice injected with 201Tl indicated a high thyroid/serum concentration ratio (T/S). The 201Tl biological half-life (t 1/2) in serum (30 - 135 s) was much shorter than in thyroid (53 - 55 h) for human subjects and experimental animals. The 1 h 201Tl T/S ratio was comparable to that of 131I and 99mTc, indicating presence of a gradient for 201Tl also. Increase of endogenous TSH induced by propylthiouracil led to a significant rise in in T/S for 99mTc, 131I and 201Tl, whereas TSH inhibition by feeding l-thyroxine led to decrease in T/S for 99mTc and 201Tl. In vitro thyroid/medium concentration ratio (T/M) of 99mTc and 201Tl was decreased after 20' incubation with ouabain, an inhibitor of the Na+, K+, activated ATP-ase. However, perchlorate in vitro or in vivo failed to diminish the 201Tl T/M ratios or to affect the t 1/2 of 201Tl in human subjects, whereas T/M of 201Tl was depressed by KCl addition to the medium.