Thyrotropin modulates low density lipoprotein binding activity in FRTL-5 thyroid cells.
FRTL-5 cells possess high affinity low density lipoprotein (LDL) receptors which bind, internalize, and degrade LDL. When FRTL-5 cells are deprived of thyrotropin (TSH) the binding of LDL increases more than 2-fold. Upon addition of TSH, at a concentration of 1 x 10(-10) M or greater, LDL binding decreases rapidly and within 24 h reaches the level which is typical of FRTL-5 cells chronically stimulated by TSH. The data available suggest that TSH-dependent down-regulation of LDL receptor activity is exerted through a reduction of the number of active LDL receptors, with no change in affinity. It is unlikely that the synthesis of LDL receptors is impaired, since LDL receptor messenger RNA is not decreased by TSH. The effect of the hormone on LDL receptor activity can be mimicked by 8-Br-cAMP and is completely abolished by the protein synthesis inhibitor cycloheximide but not by actinomycin D. TSH regulation of LDL receptor activity is lost in v-ras Ki-transformed FRTL-5 cells (Ki Mol) which also have lost TSH dependence for adenylate cyclase activation and growth. However, 8-Br-cAMP decreases LDL binding in Ki Mol FRTL-5 cells. The reduced availability of LDL receptor in TSH-stimulated FRTL-5 cells may be related to the increased membrane fluidity (Beguinot, F., Beguinot, L., Tramontano, D., Duilio, C., Formisano, S., Bifulco, M., Ambesi-Impiombato, F. S., and Aloj, S. M. (1987) J. Biol. Chem. 262, 1575-1582) or may reflect increased degradation of LDL receptors. We propose that a lower cholesterol uptake is needed in an actively proliferating cell population, to increase the production of isoprenoids whether it be for cholesterol biosynthesis or for the synthesis of other compounds requiring isoprenoid precursors.
Bifulco
M
M
Centro di Endocrinologia ed Oncologia Sperimentale/Consiglio Nazionale delle Ricerche, University of Naples, Italy.
Santillo
M
M
Tedesco
I
I
Zarrilli
R
R
Laezza
C
C
Aloj
S M
SM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D011905:Genes, ras; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051381:Rats; D011973:Receptors, LDL / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland; D013972:Thyrotropin / Q000494:pharmacology*; D013997:Time Factors
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D003609:Dactinomycin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013972:Thyrotropin; D003513:Cycloheximide