In:
European Journal of Endocrinology, Oxford University Press (OUP), Vol. 132, No. 6 ( 1995-06), p. 735-743
Abstract:
Dugrillon A, Gärtner R. δIodolactones decrease epidermal growth factor-induced proliferation and inositol-1,4,5-trisphosphate generation in porcine thyroid follicles–a possible mechanism of growth inhibition by iodide. Eur J Endocrinol 1995;132:735–43. ISSN 0804–4643 δ-Iodolactones (6-iodo-8,11,14-eicosatrienoic δ-lactone, δ-IL), an iodinated derivative of arachidonic acid, has been shown to be synthesized in thyroid tissue and to inhibit thyroid cell proliferation. It is discussed as a potential mediator of the autoregulatory pathway of iodide in cyclic adenosine-3′,5′-monophosphate (cAMP)- and thyrotropin (TSH)-independent growth. We therefore further localized the action of iodide and of δ-IL in isolated porcine thyroid follicles. Epidermal growth factor (EGF) and 12- O -tetradecanoylphorbol-13-acetate (TPA) dose dependently stimulated thyroid cell proliferation which could be inhibited by staurosporin (0.1–10 nmol/l), Iodide (2.5–40 μmol/l) as well as δ-IL (0.5–2 μmol/l) also dose dependently inhibited EGF- and TPA-induced proliferation. As the calcium ionophor A 23187 (100 pmol/l) completely abolished the inhibitory effects of iodide and of δ-IL, this may indicate a mechanism of δ-IL at or proximal to the calcium-dependent activation of protein kinase C. The growth inhibitory effect was restricted to δ-iodolactones when δ-Il was compared to 6-iodo-8,11,14,17-eicosatetraenoic δ-lactone and 5-iodo-7,10,13,16,19-docosapentaenoic γ-lactone, It could not be prevented with propylthiouracil and therefore deiodination and a different iodide action is unlikely. Inositol-1,4,5-trisphosphate (IP 3 ) and cAMP were measured in extracts from isolated porcine thyroid follicles stimulated with EGF 10 ng/ml) or TSH 1.0U/l) revealing comparable kinetics in IP 3 generation, while cAMP formation was only stimulated by TSH, δ-Iodolactone (2 μmol/l) only decreased EGF-induced IP 3 formation, whereas TSH-induced IP 3 and cAMP formation was unchanged. The γ-iodolactone which did not inhibit thyroid cell proliferation, also had no effect on IP 3 generation. These results demonstrate an action of iodide and δ-IL at the calcium-dependent signal transduction modulating thyroid cell proliferation by EGF but not TSH. δ-Iodolactone acts at or proximal to the generation of IP 3 induced by EGF, whereas the TSH-dependent signal transduction seems to be unaltered. δ-Iodolactone may therefore be speculated as a specific inhibitory mediator of iodide on growth factor-induced thyroid cell proliferation. Alex Dugrillon, Zentrallabor der Medizinischen Klinik und Poliklinik, University of Heidelberg, Bergheimer Str. 58, D-69115 Heidelberg. Germany
Type of Medium:
Online Resource
ISSN:
0804-4643
,
1479-683X
DOI:
10.1530/eje.0.1320735
Language:
Unknown
Publisher:
Oxford University Press (OUP)
Publication Date:
1995
detail.hit.zdb_id:
1485160-X
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