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.

Catecholamine inhibition of thyrotropin-induced secretion of thyroxine: mediation by an alpha-adrenergic receptor.

Thyroxine secretion by mouse thyroid gland incubated in vitro was measured. Thyrotropin or dibutyryl cAMP increased thyroxine secretion several-fold. l-Epinephrine and l-norepinephrine strongly inhibited this stimulated release; l-isoproterenol was relatively ineffective. Phentolamine prevented the inhibition by catecholamines of thyroxine release; l-propranolol had no effect. These findings indicate that stimulation of alpha-adrenergic receptors opposes the action of thyrotropin in the regulation of thyroxine secretion.

Mediation by serotonin of gold thioglucose-induced necrosis of the ventromedial hypothalamus.

Agents that lower serotonin levels or inhibit serotonin action prevent GTG-indurea and that such damage leads to abnormally increased capillary permeability. Since the VMH is rich in serotonin and since serotonin is a potent oedema-producing agent mice, these findings indicate that the production of necrosis by GTG is mediated by release of serotonin from the damaged pericapillary processes.

Gold thioglucose obesity syndrome.

Parenteral administration of gold thioglucose to mice produces an area or necrosis in the ventromedial portion of the hypothalamus. The lesion, like lesions produced by electrocautery of this area, causes hyperphagia and consequent obesity. The glucose moiety of gold thioglucose is essential for production of the lesion. Glucose analogues (2-deoxy-glucose, sodium thioglucose and phlorizin) prevent the gold thioglucose-induced lesion, and by themselves produce a transient hyperphagia. Insulin deficiency prevents the lesion. Either adrenalectomy or hypophysectomy counteracts the effect of insulin deficiency. Electron microscopic studies, in which general necrosis is avoided by administration of aspirin before gold thioglucose or by administration of subnecrotic doses of gold thioglucose, reveal that gold thioglucose primarily affects neural elements contiguous with capillaries in the ventromedial hypothalamus. The experimental observations indicate the presence of special glucoreceptor cells in the ventromedial hypothalamus that are involved in the regulation of food intake.

Action of gold thioglucose on pericapillary structures in the ventromedial hypothalamus.

The administration of GTG to mice leads to death of all structures in a circumscribed area of the VMH as a result of loss of blood circulation. The loss of circulation is due to damage by GTG of neural processes adjacent to some of the capillaries in this area; damage to these processes leads to abnormal capillary permeability. Pericapillary damage occurs under conditions where capillary damage and consequent necrosis are prevented. Abnormal capillary permeability appears to follow release of a vasoactive substance from the damaged neural processes. Damage to the pericapillary neural processes by GTG is insulin-dependent and is counteracted by glucocorticoids.