Cooling enhances adenosine 3':5' monophosphate accumulation in thyrotropin stimulated dog thyroid slices

Dog thyroid slices have been stimulated in vitro by thyrotrophin (TSH) at 37 degrees C and 25 degrees C. Adenosine 3':5'-monophosphate (cyclic AMP) accumulation was enhanced by cooling to 25 degrees C. This observation has been extended to kidney cortex slices stimulated by parathyroid hormone (PTH). However, this phenomenon is not general: it does not apply to thyroid slices stimulated by prostaglandin E1 (PGE1) or adrenal cortex slices stimulated by adrenocorticotrophic hormone (ACTH). Slight cooling provides a useful tool to influence biochemical mechanisms in intact cells and therefore the mechanism of action of cooling on cyclic AMP was investigated in dog thyroid slices stimulated by TSH. Adenylate cyclase and cyclic nucleotide phosphodiesterase activities as measured in acellular preparations decreased in parallel with the temperature. A decrease of the cyclic AMP efflux from the cell at 25 degrees C, although not measurable in this preparation, did not seem to be responsible for the phenomenon. computer simulation of the kinetics of the cyclic AP accumulation curve is compatible with the hypothesis of decrease in the desensitization rate of adenylate cyclase at 25 degrees C. This was demonstrated using an experimental protocol in intact slices and by measurements of adenylate cyclase activities in particulate preparations of slices pretreated or not by the hormone. This decreased adenylate cyclase desensitization can explain the higher cyclic AMP levels in TSH stimulated thyroid slices incubated at 25 degrees C. However, this does not exclude complementary mechanisms.