The effect of methoxamine, a specific alpha 1-adrenergic agonist, on the release of T3, T4 and cAMP from perifused mouse thyroid was studied to clarify the role of the alpha 1-adrenergic receptor in the regulation of thyroid hormone secretion. TSH-stimulated T3 and T4 release was inhibited significantly by methoxamine. With regard to cAMP release, methoxamine inhibited TSH-stimulated cAMP release in the presence of 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone but did not inhibit TSH-stimulated cAMP release in the presence of 3-isobutyl-1-methylxanthine. Methoxamine did significantly suppress TSH-stimulated release of T3 and T4 in the presence of each phosphodiesterase inhibitor. Depletion of Ca2+ in the perifusion buffer abolished completely the inhibitory effect of methoxamine on TSH-stimulated T3 and T4 release. The present study suggests that activation of the alpha 1-adrenergic receptor inhibits TSH-stimulated T3 and T4 secretion through a Ca(2+)-dependent mechanism in the mouse thyroid gland.
We examined the effect of noradrenaline on the release of 3,5,3'-tri-iodothyronine (T3) and thyroxine (T4) from perifused mouse thyroid. Noradrenaline suppressed the thyrotrophin (TSH)-stimulated release of T3 and T4. The addition of prazosin, which is a specific alpha 1 antagonist, or the depletion of Ca2+ from the perifusion buffer completely abolished the inhibitory effect of noradrenaline on TSH-stimulated T3 and T4 release. Noradrenaline did not inhibit TSH-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) release in the presence of 3-isobutyl-1-methylxanthine (IBMX), which inhibits both cAMP-specific and calmodulin-sensitive phosphodiesterases. Noradrenaline significantly suppressed the TSH-stimulated release of T3 and T4 in the presence of IBMX. These results suggest that the inhibitory effect of noradrenaline on TSH-stimulated T3 and T4 release is not mediated through a cAMP-dependent process or the activation of a calmodulin-sensitive phosphodiesterase, and that this inhibition is mediated through a Ca(2+)-dependent process regulated by the alpha 1-adrenergic system in the mouse thyroid.
The effect of the ionophore A23187 on a. the release of thyroid hormone from perifused mouse thyroid glands and b. the morphological changes in follicular epithelial cells was evaluated. A23187 at a concentration of 5 \g=m\mol/lsignificantly inhibited both the TSH-and the forskolin-stimulated release of T3 and T4. In the presence of 3-isobutyl-1-methylxanthine or (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) RO 20-1724, A23187 did not affect the forskolin-stimulated release of cAMP, but did inhibit the release of T3 and T4 stimulated by forskolin. Light and electron microscopic evaluation of the follicular epithelial cells of mouse thyroid tissues following 1-h stimulation with forskolin showed numerous pseudopods engulfing luminal colloid of various size and the presence of reabsorbed colloid droplets in the apical cytoplasm. Quantitative electron microscopic analysis revealed that the addition of the ionophore A23187 reduced the number of reabsorbed colloid droplets to one eighth in follicular epithelial cells. These observations suggest that the increase in intracellular Ca2+ induced by the ionophore A23187 inhibits the TSH-stimulated thyroid hormone release independently of the cAMP level, and that the suppression of thyroid hormone release may be due to an inhibition of colloid reabsorption. Intracellular Ca + plays an important role in the regulation of cell function in many biological sys¬ tems, especially in respect to exocytosis and secre¬ tion (1). However, an inhibitory effect of an in¬ crease in intracellular Ca2+ in the thyroid has been reported (2-4). The ionophore A23187 and carbamylcholine, both of which increase the influx of calcium, inhibit the TSH-stimulated production of cAMP (2-4) and the secretion of iodine (4). We re¬ cently showed that, in rat thyroid glands, A23187 inhibited both the TSH-induced morphological changes in the follicular epithelial cells and the TSH-stimulated release of T3 without reducing the cAMP level (5).The present experiment was designed to inves¬ tigate further the mechanism by which an increase in intracellular Ca2+ attenuates the release of thy¬ roid hormone using a mouse thyroid perifusion system, which has been found useful in studying thyroid function in vitro (6). In this experiment, we quantitatively evaluated the ultrastructural changes induced by forskolin in the follicular epi¬ thelial cells with dynamic observation of the release of thyroid hormone by the agent. Materials and MethodsPerifusion of the mouse thyroid gland was performed as previously described (5-8). Thyroid glands were obtained from BALB/c or ddY mice (8-10 weeks) under ether an¬ esthesia. The excised glands were pre-incubated in KrebsRinger bicarbonate buffer, pH 7.4, containing 0.1% glu¬ cose and 0.3% BSA (KRBG) at 37°C for 90 min. Twenty pre-incubated thyroid halflobes were placed in a chamber and perifused with the same buffer at a flow rate of 1.9 ml/20 min. KRBG was used as the infusion buffer for an initial period of 60 min. After washing with Ca2+-free KRBG for 10 min, the buffer...
We studied the histology and the pathogenic mechanism of black thyroid induced in rats by oral administration of 2,4-diaminoanisole sulfate (DAAS), a component of permanent hair dye. Histochemical examination of thyroids of rats fed for 6 weeks with DAAS showed that the black pigments were localized in the follicle epithelial cells, and stained positively by Fontana-Masson's method. Ultrastructural study disclosed electron dense deposits in lysosomes of these cells. Determination of serum levels of T4, T3 and TSH revealed a suppressed thyroid function in DAAS-treated rats. No black discoloration occurred in thyroid glands when DAAS was given with a regular diet containing propylthiouracil (PTU) or thyroid powder, or with a low iodine diet. The black discoloration of DAAS solution was accelerated in virro in the presence of H20; by lactoperoxidase in a dose-dependent manner. The results suggest that thyroid peroxidase (TPO) plays an essential role in the discoloration and that the black discoloration of the thyroid gland is related to the iodine metabolism. We conclude that pigmentation of therthyroid gland induced by oral administration of DAAS is due to deposition of oxidized derivatives of DAAS in lysosomes in follicle epithelial cells, resulting in a suppressed thyroid function.2,4-Diaminoanisole sulfate (DAAS; 4-Methoxy-mphenylenediamine sulfate) was first studied on its mutagenic effect in animals by oral administration; the agent was also reported to cause the black discoloration of the thyroid gland (6, 7, 17). Minocycline, an antibiotic, has also been known to induce the black discoloration of the thyroid gland (black thyroid) in both animals (3, 8) and humans (2). Although thyroid pigment granules were previously reported to be composed of melanin (11, 13) or lipofuscin (2, 12), our morphological and biochemical studies on minocycline-induced black thyroid have clearly demonstrated that the pigment granules are composed of a metabolic derivative of minocycline itself (14). However, the mechanism of black discoloration of the thyroid gland and the effect of the discoloration on the thyroid function still remained unclear.To further clarify the pathophysiology of the black thyroid, we investigated in this study the histology and mechanism of DAAS-induced thyroid pigmentation and its effect on the thyroid function. MATERIALS AND METHODSMale Sprague-Dawley rats purchased from Japan SLC (Shizuoka, Japan) were used. The animals were kept at a temperature of 25°C at 55% relative humidity and under a controlled 12-h light cycle.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.