Effect of okadaic acid and calyculin-A, two protein phosphatase inhibitors, on thyrotropin-stimulated triiodothyronine secretion in cultured sheep thyroid cells.
We have studied the effect of two protein phosphatase inhibitors on thyrotropin (TSH)-stimulated triiodothyronine (T3) production by sheep thyroid cells grown in primary culture. Incubation of sheep thyrocytes with okadaic acid (OA) and calyculin-A (CL-A), two potent inhibitors of type 1 (PP1) and type 2A (PP2A) protein phosphatases, resulted in an increase of TSH-stimulated T3 production. This effect was detected using concentrations as low as 0.1 pM with OA and 1 fM with CL-A. An inhibitory effect on T3 production, due to cellular death, was observed with 6 nM OA and 1 nM CL-A. In the absence of TSH, OA or CL-A had no effect on T3 production by thyrocytes. Forskoline (10 microM), an activator of adenylate cyclase, increased the basal and TSH-stimulated T3 release by sheep thyroid cells; this effect was increased by OA in cells grown in the basal state but not in the presence of TSH. These results suggest that the marine toxins OA and CL-A, two potent inhibitors of PP-1 and PP-2A, have significant stimulatory effects on T3 secretion promoted by TSH and FK. These observations indicate that these proteins could be important mediators of thyroid hormone production.
Arufe
M C
MC
Departamento de Biología Funcional y Ciencias de la Salud, Universidad de Vigo, Spain.
Beckett
G J
GJ
Durán
R
R
Alfonso
M
M
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008387:Marine Toxins; D019319:Okadaic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D012756:Sheep; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D014284:Triiodothyronine / Q000096:biosynthesis / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D014284:Triiodothyronine; D005576:Colforsin; D019319:Okadaic Acid; C059041:calyculin A; D013972:Thyrotropin; D010749:Phosphoprotein Phosphatases