Pairs of cyclic AMP analogs, that are specifically synergistic for type I and type II cAMP-dependent protein kinases, mimic thyrotropin effects on the function, differentiation expression and mitogenesis of dog thyroid cells.
The role of the two different isozymes of the cAMP-dependent protein kinase is still unclear. We have investigated the potential roles for each isozyme in dog thyroid cells, a model in which the function, expression of differentiation and proliferation are positively regulated by thyrotropin acting through cyclic AMP. The dog thyroid contains both type I and type II cAMP-dependent protein kinases. These isozymes were selectively activated in vitro by type-I-directed and type-II-directed analog pairs. In thyroid slices, both type-I directed and type II-directed analog pairs synergistically activated thyroid hormone synthesis, as measured by incorporation of 131I into proteins and thyroid hormone secretion as determined by the release of butanol-extractable 131I. In primary cultures of dog thyroid cells both isozyme-directed analog pairs synergistically enhanced iodide trapping, a marker of differentiation, and DNA synthesis, as measured by the percentage of cells incorporating [3H]thymidine into their nuclei. However, DNA synthesis was more sensitive to type-I-directed pairs. The results demonstrate that both cAMP-dependent protein kinase isozymes can mediate the action of cAMP on function, differentiation expression and cell proliferation in dog thyroid cells.
Van Sande
J
J
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Lefort
A
A
Beebe
S
S
Roger
P
P
Perret
J
J
Corbin
J
J
Dumont
J E
JE
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004285:Dogs; D004357:Drug Synergism; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007454:Iodides / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*
D007454:Iodides; D007527:Isoenzymes; D013972:Thyrotropin; D000242:Cyclic AMP; D011494:Protein Kinases