ABSTRACT
Objective:Exploring the role of thyrotropin receptor(TSHR) in lipotoxicity-induced thyroid function damage.Methods:Rat thyroid follicular epithelial cells(RTC) were stimulated with different doses of palmitic acid(PA), and the lipid content of the cells was observed through Oil Red O staining. The expression levels of TSH receptor(TSHR), Ttf1, and SSBP1 mRNA and protein in each group were detected using RT-PCR and Western blot. The TSHR protein level in the cell culture supernatant was measured using ELISA. Membrane TSHR was assessed through immunofluorescence and compared with the control group. We used PA to stimulate the TSHR over-expression(TSHR OE) and normal RTC, as PA+ TSHR OE group and PA group respectively, then testing Tg mRNA and protein, cAMP and Tg in cell supernatants levels, then comparing with the control.Results:RTC were stained into peau d′orange in PA groups. Compared with the control group, we found TTf1, SSBP1 and TSHR mRNA as well as protein levels in PA groups were decreased(all P<0.05), TSHR of the cell membrane and supernatants were reduced(all P<0.05), characterizing dose-dependent changes partly. Moreover, we found in PA group Tg mRNA level was downregulated( P<0.05), Tg protein levels were reduced in the supernatants and cells( P<0.05), cAMP level was decreased in cells( P<0.05); in TSHR OE group, Tg mRNA level was upregulated( P<0.05), Tg protein levels in cells and supernatants were increased(all P<0.05), cAMP level was similar. Compared with the PA group, we found in PA+ TSHR OE group Tg mRNA level was upregulated( P<0.05), Tg protein levels were increased in the supernatants and cells(all P<0.05), cAMP level was elevated in cells( P<0.05). Conclusion:PA induces lipid deposition in RTC, decreased synthesis and secretion of Tg. This effect is likely achieved through the downregulation of the TSHR/cAMP signaling pathway.
ABSTRACT
Objective To investigate the circadian change of autonomic nervous system in hyperthyroidism (HT) patients. Methods Recording 24 h dynamic electrocardiography from 33 HT patients( HT group) and 35 controls (control group). The cardiac autonomic nervous function was evaluated by the time domain and frequency domain analysis of heart rate variability( HRV). Results Comparing with control group, the SDNN, SDANN, ASDNN and rMSSD were significantly lower in HT group[ (82.3 ± 29.0)ms vs. (139.4±40.2 ) ms, ( 75.0 ± 27.4) ms vs. ( 130.3 ± 43.9) ms, (29.9 ± 14.9 ) ms vs. (57.3 ± 14.4) ms,( 19.8 ± 10.9 ) ms vs. (29.5 ± 9.4) ms ] (P ＜ 0.01 or ＜ 0.05 ), the long term total power (TP), high frequency (HF), low frequency (LF) and very low frequency (VLF) were significantly lower in HT group [ (566.1±573.2) ms2/Hz vs. ( 1894.2 ± 984.3)ms2/Hz, (68.1 ± 88.9 ) ms2/Hz vs. (232.7 ± 155.5 ) ms2/Hz, ( 127.4 ±163.0) ms2/Hz vs. (551.3 ± 390.6) ms2/Hz, (330.3 ± 300.6) ms2/Hz vs. (1073.2 ± 570.2) ms2/Hz] (P ＜0.01 ). Comparing with control group, short term VLF was higher in HT group during most time in 24 hours (P＜ 0.05 ). Short term LF was higher in HT group mainly in day time (P＜ 0.05 ). Short term HF was higher in HT group occasionally in the whole day (P＜0.05). Short term LF/HF didn't show significant difference between HT group and control group at most time points (P＞0.05).Conclusion In HT patients, cardiac chronotropic property is impaired, sympathetic activity increases in whole day, vagal activity increases correspondently but the increase in day is more marked than that in night.