Thyrotropin upregulates alpha 1-adrenergic receptors in rat FRTL-5 thyroid cells.
FRTL-5 rat thyroid cells grown and maintained in a medium containing 0.05 nM thyrotropin have a 10-fold higher number of alpha 1-adrenergic receptors on their cell surface than FRTL-5 cells maintained in the absence of thyrotropin in their medium. The increased number of alpha 1-adrenergic receptors, measured as increased specific [3H]prazosin binding per microgram of DNA, is not associated with any changes in Kd values for prazosin. Thyrotropin increases the number of alpha 1-adrenergic receptors by inducing their biosynthesis, as evidence by the inhibitory effects of cycloheximide or actinomycin D; the effect on biosynthesis is cAMP-mediated, since 8-bromoadenosine 3',5'-cyclic monophosphate, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine can mimic the thyrotropin effect in both extent and time course. The alpha 1-adrenergic receptors on FRTL-5 thyroid cells have been functionally linked to iodide efflux into the follicular lumen and to the iodination of thyroglobulin--i.e., to the formation of thyroid hormones; the alpha 1-adrenergic receptor signal is mediated by Ca2+ rather than by cAMP and involves arachidonic acid intermediates. The present data thus describe a unique upregulation phenomenon wherein the sequential expression of two receptors (thyrotropin and alpha 1-adrenergic) and two distinct signal systems (cAMP and Ca2+) are apparently a necessary prelude to thyroid hormone homoeostasis.
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D011224:Prazosin; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000096:biosynthesis* / Q000187:drug effects; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects*; D013972:Thyrotropin / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; C030013:cactinomycin; D003609:Dactinomycin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013972:Thyrotropin; D002772:Cholera Toxin; D003513:Cycloheximide; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine; D011224:Prazosin