Dual activation by thyrotropin of the phospholipase C and cyclic AMP cascades in human thyroid.
In human thyroid slices prelabeled with myo-[2-3H]inositol, thyrotropin (TSH, 3-30 mU/ml) stimulated IP3, IP2 and IP1 generation over a prolonged time course. The cAMP response was much more sensitive to TSH, peaking between 1 and 5 mU/ml. Forskolin (10(-5) M) and isoproterenol had no effect on basal IP levels, while carbamylcholine (10(-5) M, 10(-4) M) also increased IP accumulation. These data suggest that in the human thyroid, TSH activates a phospholipase C generating IP3 and diacylglycerol independently of the well-known adenylate cyclase stimulation. They validate in the human model a dual mode of action of the hormone previously proposed on the basis of indirect observations.
Laurent
E
E
Institute of Interdisciplinary Research, School of Medicine, Hospital Erasme, Brussels, Belgium.
Mockel
J
J
Van Sande
J
J
Graff
I
I
Dumont
J E
JE
D000242:Cyclic AMP / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D013972:Thyrotropin; D000242:Cyclic AMP; D010738:Type C Phospholipases