Evidence for induction by cortisol in vitro of a protein inhibitor of transport and phosphorylation processes in rat thymocytes.
Studies of intact rat thymocytes incubated in vitro with cortisol, actinomycin D, puromycin, and cycloheximide indicate that distinct inhibitory effects of cortisol on transport and phosphorylation are due to an action on mRNA synthesis with consequent induction of synthesis of protein(s) with inhibitory influence. Incubation of thymocytes with cortisol results in inhibition of the rate of labeled orthophosphate incorporation into ATP and the entry of rubidium ion and hexoses into the cells. Continuing protein synthesis is required for the progressive and persistent manifestation of the inhibitory effects of the steroid. RNA synthesis is also required during the initial phase of incubation of cells with cortisol, but significant inhibitory effects of cortisol, once initiated, are evident for at least 60-120 min after addition of actinomycin D. In contrast, addition of cycloheximide some time after cortisol results in prevention or reversal of the effects of the steroid. In the absence of cortisol, the antibiotics exert relatively little effect on orthophosphate incorporation and on the transport processes studied. It is suggested that the sequence of events leading to dissolution of thymocytes exposed to cortisol is initiated by the synthesis of mRNA coding for inhibitory protein(s) with more rapid turnover rates than that of the mRNA, and that these events are modulated by the relative sensitivity of different cellular processes to the protein inhibitor(s).
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects*; D002247:Carbon Isotopes; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism; D006601:Hexoses; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010710:Phosphates / Q000378:metabolism; D010759:Phosphorus Isotopes; D011691:Puromycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011868:Radioisotopes; D051381:Rats; D012413:Rubidium; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D014529:Uridine / Q000378:metabolism
D002247:Carbon Isotopes; D006601:Hexoses; D007461:Iodoacetates; D010710:Phosphates; D010759:Phosphorus Isotopes; D012333:RNA, Messenger; D011868:Radioisotopes; D014316:Tritium; D003609:Dactinomycin; D011691:Puromycin; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D012413:Rubidium; D005998:Glycine; D014529:Uridine; D006854:Hydrocortisone