Inhibition of Thyrotropin- and Dibutyryl Cyclic AMP-Induced Secretion of Thyroxine and Triiodothyronine by Catecholamines¹²

Abstract

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.

Efferent Neuroendocrine Pathways of Sympathetic Superior Cervical Ganglia

“…Therefore, the most feasible interpretation for these results is that the NE released local ly at the level of thyroidal acini modifies negatively the re sponse of thyroid cells to TSH. The present observations agree with some [5,32,47] but not all [35] the studies on the effects of catecholamines on thyroid function, and correlate well with our prior findings on an impending increase of sensitivity of thyroid cells to endogenous or exogenous TSH in chronically SCGx rats [42], The effect of NE could be ex erted on ther acini themselves (as revealed by in vitro studies) [32] or be partly explained by the vascular changes brought about by endogenous catecholamine release inas much as a decrease in blood flow, estimated by 86Rb uptake, was found in the thyroid gland during the degeneration of sympathetic nerve terminals after SCGx (table III).…”

“…In humans both stimulatory and inhibitory effects of epinephrine were reported; an acute injection increased 1311 uptake whereas a continuous infusion depressed it [23]. In vitro and in vivo experiments have shown that epinephrine and NE can stimulate [27,31,33,49], inhibit [5,32,47] thy roid function or be devoid of influence on it [1], For exam ple, micromolar concentrations of N E added to the incuba tion medium of thyroid glands inhibited TSH-induced se cretion of thyroid hormones [32]. Our present results indi cate that during NE release from degenerating sympathetic varicosities in the thyroid gland (as measured by the decline in NE content, fig.…”

Mechanism for the Inhibitory Action of 2-Deoxy-Glucose on Thyroid Hormone Secretion in the Mouse

“…Our suggestion is, besides our present results, also based on the fact that adrenergic nerve terminals occur in close connection to the follicular cells [II. 22,23] and that previous pharmacological investigations have shown that exogenous administration of norepinephrine inhibits TSH-induced thyroid hormone secre tion in the mouse [1,4], Furthermore, norepinephrine has been demonstrated to inhibit TSH-induced thyroid hormone secre tion from mouse thyroid in vitro by an effect antagonized by phentolamine but not by propanolol [19,20] and probably exerted by ai-adrenoceptors [26,27], Also, TSH-induced accu mulation of cyclic AMP in human thyroid cells has been shown to be inhibited by norepinephrine [33].…”

“…In con trast, a reduction of TSH-induced thyroid hormone release has been obtained by norepinephrine [4,[19][20][21] and carbachol [2,7,25]. Furthermore, electrical nerve activation has been found to increase basal thyroid hormone secretion in some experi mental systems [ 15,24], but not in others (31 ], whereas its effect on TSH-induced thyroid hormone release has not been studied.…”

Role of the Sympathetic Nervous System in the Control of Thyroid Compensatory Growth of Normal and Hypophysectomized Rats

“…In view that ipsilateral SCGx of hemiTx rats pre vented the decrease of circulating T4 as a consequence of partial thyroid removal, a permissive effect of SCG abla tion on thyroid hormone response to TSH can be put forth. Indeed, in an experimental paradigm resulting in thyroid sympathetic nerve terminal degeneration with concomitant release of nerve varicosity content in the vicinity of thyroid follicles, TSH-induced T4 secretion decreased markedly [5]; likewise, NE depressed thyroid secretory response to TSH in vitro [24,28]. Further experiments assessing the time course for the effect of bilateral SCGx on circulating TSH and T4 concentrations would strengthen these conclusions.…”