Thyroid hormone receptor occupancy and biological effects of 3,5,3,-L-triiodothyronine (T3) in GH4C1 rat pituitary tumour cells.
The GH4C1 pituitary cell line, an excellent model for a thyroid hormone action study, was used for determination of the relationship between thyroid hormone receptor occupancy and intensity of cell proliferation, prolactin (PRL) production, thyrotropin (TSH) inhibition and 3,5,3,-L-triiodothyronine (T3) receptor down-regulation. Nuclear receptor population was progressively occupied by T3 in concentrations ranging from 0.025 to 10.0 nM T3. Bmax ranged from 0.029 fmol/10(6) cells at the lowest T3 concentration to Bmax = 12.51 fmol/10(6) cells at the highest concentration. Each of the observed biological events is operative within distinct dose-response ranges in cultured GH4C1 cells. The maximal biological response (except the TSH inhibition and T3 receptor down-regulation) does not require the occupation of the whole nuclear receptor population by T3 and the intensity of none of the responses studied was directly proportional to thyroid hormone receptor occupancy.
Filipcík
P
P
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Strbák
V
V
Brtko
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000096:biosynthesis; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000096:biosynthesis; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D011388:Prolactin; D013972:Thyrotropin