Regulation of thyrotropin (TSH) release and production in monolayer cultures of transplantable TSH-producing mouse tumors.
Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D051379:Mice; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009711:Nucleotides / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D013972:Thyrotropin / Q000096:biosynthesis / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D014184:Transplantation, Homologous; D014284:Triiodothyronine / Q000494:pharmacology
D009711:Nucleotides; D011458:Prostaglandins E; D014284:Triiodothyronine; D013004:Somatostatin; D013972:Thyrotropin; D013806:Theophylline; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D013974:Thyroxine; D002118:Calcium