Epinephrine: effect on uptake of iodine by dispersed cells of calf thyroid gland.

In isolated thyroid cells I-epinephrine (0.1 and 10.0 micrograms per milliliter), norepinephrine and isoproterenol consistently stimulated the accumulation and organic binding of iodine. The effect was partially inhibited by phentolamine, but not propranolol, and hence may be mediated by alpha receptors. Theophylline did not mimic or enhance the epinephrine effect, suggesting that the latter may not result from activation of adenyl cyclase.

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.

Acetylcholine and norepinephrine: compared actions thyroid metabolism.

Acetylcholine (ACh; 5 X 10(-4) M), like norepinephrine (NE; 6 X 10(-6) M), as shown previously, stimulated iodide organification by mouse thyroids in vitro, while at the same time it inhibited TSH- or (Bu)2cAMP-induced T4 release. However, thyroid cAMP was not changed by ACh, suggesting that ACh, like NE, exerted its effects at a step beyond cAMP production. Also, while ACh increased cGMP concentrations, (Bu)2cGMP and 8-bromo-cGMP were not effective on thyroid function in this system. Neurotransmitters, then, presumably do not exert their action through cyclic nucleotide stimulation ACh-induced stimulation of organification and inhibition of release was reversed by 10(-5) M atropine (ATR) but not by 10(-5) M d-tubocurarine, indicating that muscarinic receptors were involved. ATR also reversed inhibition of T4 release induced by NE, suggesting that the presynaptic cholinergic pathway may be responsible for stimulation of postsynaptic cholinergic and adrenergic neurotransmitters in the thyroid gland.

Calcium depletion stimulates thyroxine release from the thyroid.

Excised mouse thyroids incubated in Ca++-free medium were stimulated to release increased amounts of stable thyroxine. This stimulation of thyroxine release by incubated thyroid tissue was not additive with TSH or (Bu)2cAMP. It was reversed by norepinephrine through an alpha adrenergic receptor, similar to TSH or (Bu)2cAMP stimulation. Depletion of Ca++ did not result, however, in an increase in the concentration of cAMP in incubated thyroid glands, suggesting that its locus of action was subsequent to TSH stimulation or cAMP production.

Norepinephrine and thyrotropin effects on the thyroid in vitro: simultaneous stimulation of iodide organification and antagonism of thyroxine release.

Norepinephrine (NE), which has previously been shown to inhibit TSH-induced T4 release by mouse thyroids in vitro, was found to stimulate iodide organification. The concentration of NE (6 X 10(-7) M) necessary to stimulate organification of iodide was 10 times less than the concentration (6 X 10(-6) M) required for inhibition of TSH-induced T4 release. Both actions of NE were exerted through an alpha-adrenergic receptor, since they were inhibited by phentolamine but not by l-propranolol. One milliunit of TSH maximally stimulated T4 release only, but larger amounts (100 mU) also stimulated organification. TSH stimulation of T4 release and organification was not affected by adrenergic antagonists and therefore was not mediated by adrenergic receptors. N6, O2-Dibutyryl cAMP and isobutylmethylxanthine, like TSH, stimulated T4 release. Their actions were inhibited by NE. However, both compounds, unlike TSH, failed to enhance organification in mouse thyroids. The effects of TSH and NE on the cAMP content of incubated mouse thyroids were also studied. TSH induced a prolonged increase in thyroidal cAMP during the 90-min incubation; this increase was unaffected by alpha- or beta-adrenergic antagonists. In contrast, NE (6 X 10(-5) M) produced a transient but significant increase in cAMP only within the first 5 min. Unlike the action of NE on organification, this short term stimulatory effect on cAMP production was mediated by a beta-adrenergic receptor, since it was blocked by l-propranolol but not by phentolamine. The following conclusions were reached: 1) stimulation of iodide organification and thyroid hormone release involves different sensitivity thresholds for TSH and NE; 2) TSH stimulation of iodide organification, hormone release, and cAMP formation is not exerted through adrenergic receptors; 3) NE stimulates organification and inhibits TSH-stimulated T4 release through alpha-adrenergic receptors, but stimulates cAMP production through beta-receptors; and 4) cAMP may not be the mediator of all TSH actions on the thyroid.

Dopamine and L-dopa: inhibition of thyrotropin-stimulated thyroidal thyroxine release.

Previous studies had suggested that norepinephrine (NE) and its precursors dopamine (DA) and L-DOPA acted similarly on iodine metabolism of isolated thyroid cells. Present studies indicate that this similarity extends to the inhibition by catecholamines of TSH-stimulated T4 release by mouse thyroids incubated in vitro. DA (5 X 10(-4) M), like NE, shown previously, inhibits TSH-stimulated T4 release. This inhibition was reversed by the alpha-blockers phentolamine, prazosin, and yohimbine, but not by the beta-blocker L-propranolol. DU-18288 and diethyldithiocarbamate, inhibitors of DA beta-hydroxylase, did not reduce DA inhibition, suggesting that prior conversion to NE was not a condition for DA activity. Apomorphine, a dopaminergic agonist but not a NE precursor, acted like DA, and its inhibition was also reversed by alpha-blockers. Furthermore, sulpiride, a dopaminergic blocker, reversed DA and apomorphine inhibition of TSH stimulation. These results suggest that DA inhibits TSH-stimulated T4 release through both adrenergic and dopaminergic receptors. On the other hand, L-DOPA, exerting an inhibition like that of DA, was also reversed by alpha-blockers, but its activity was greatly diminished by carbidopa, an inhibitor of aromatic L-amino acid decarboxylase, the enzyme converting L-DOPA to DA. This indicated that L-DOPA had to be converted to DA for activity. Both DA and L-DOPA inhibited stimulation of T4 release induced by (Bu)2cAMP, suggesting that their effect was exerted at a locus distal to cAMP generation. Indirect confirmation of a cAMP-independent pathway was obtained when DA inhibited TSH-stimulated cAMP formation, but, contrary to T4 release, this inhibition was not reversed by dopaminergic or adrenergic blockers. Presumably, therefore, DA inhibition of TSH-stimulated cAMP production was not related to T4 release. We conclude that 1) DA inhibits TSH-stimulated T4 release in mouse thyroids via alpha-adrenergic and dopaminergic receptors; 2) L-DOPA has to be converted to DA to produce inhibition; and 3) cAMP is unlikely to be an intermediary in DA inhibition.

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.

Cerebral perfusion in early and late opiate withdrawal: a technetium-99m-HMPAO SPECT study.

The purpose of this study was to determine if cerebral blood flow (CBF) alterations are associated with discontinuation of heroin in chronic heroin users, and whether these alterations are reversible during abstinence. Ten physically healthy opioid-dependent males, hospitalized on an inpatient drug rehabilitation unit, were studied. Each patient had an initial single photon emission computed tomographic (SPECT) scan with the radiotracer technetium-99m-d,l-hexamethylpropyleneamine oxime (99mTc-HMPAO) 1 week after opiate discontinuation and a repeat scan 2 weeks later. The initial scans in 9 of the 10 subjects demonstrated significant, often discrete, perfusion defects, especially in the frontal, parietal, and temporal cortices. Two weeks later, repeat brain perfusion SPECT scans showed improvement in all nine subjects who had abnormal scans. Comparisons of the first scan with the second scan showed an increase in cortical uptake on the repeat SPECT study. All subjects had normal computed tomographic or magnetic resonance imaging scans. The results of this preliminary study suggest that the chronic use of opiates, like chronic use of cocaine, results in perfusion abnormalities without corresponding abnormalities on imaging studies of cerebral anatomy and morphology. This study also documents that these perfusion defects are partially reversible with short-term abstinence.

Incidental detection of adult polycystic kidney disease on routine bone scan.

A routine bone scan performed on a 36-y old male incidentally demonstrated enlarged kidneys with multifocal areas of radionuclide concentration suggestive of polycystic kidneys. Further evaluation using ultrasonography, CT scan, and a 99mTc-GHA renal scan confirmed the initial impression. The routine evaluation of the kidneys on a bone scan is emphasized as a simple method of identifying previously unsuspected renal structural abnormalities.