The interactive effects of ethinylestradiol and progesterone on transcriptional expression of genes along the hypothalamus–pituitary–thyroid axis in embryonic zebrafish (Danio rerio)

Tris(2-chloroethyl) Phosphate Exerts Hepatotoxic Impacts on Zebrafish by Disrupting Hypothalamic–Pituitary–Thyroid and Gut–Liver Axes

“…38,39,81,82 Because the synthesis of thyroid hormones is primarily regulated by TRH and TSH, which are secreted by the hypothalamus and pituitary gland, respectively, the disturbance of T3 and T4 may be due to TCEP-induced suppression of TRH and TSH. 38,83 In this study, disruption of the HPT axis was further confirmed by the expression analysis of its target genes. expression levels of tshβ, dio1, dio2, and tg in the fish brain were significantly upregulated by TCEP exposure.…”

“…Because all of these genes encode molecules that positively regulate the HPT axis, their upregulation could be a feedback response to the disrupted HPT axis. ,− For instance, upregulation of tshβ might be a response at the transcriptional level to compensate for the decline of TSH in the brain. Similarly, since dio 1 and dio 2 encode deiodinases that catalyze the transformation of T4 to T3, their upregulation could be a response to the disequilibrium of T3 and T4. , Furthermore, the expressions of ttr , trα , and trβ in the zebrafish liver were also significantly altered by TCEP exposure, indicating a disrupted regulatory function of the HPT axis in the liver. For example, the suppression of ttr , which encodes the thyroid hormone transporter transthyretin, suggests that the transportation of thyroid hormones in the liver is obstructed by TCEP exposure .…”

“…Similarly, since dio 1 and dio 2 encode deiodinases that catalyze the transformation of T4 to T3, their upregulation could be a response to the disequilibrium of T3 and T4. 83,87 Furthermore, the expressions of ttr, trα, and trβ in the zebrafish liver were also significantly altered by TCEP exposure, indicating a disrupted regulatory function of the HPT axis in the liver. For example, the suppression of ttr, which encodes the thyroid hormone transporter transthyretin, suggests that the transportation of thyroid hormones in the liver is obstructed by TCEP exposure.…”

“…First, in addition to the significantly lower levels of TRH and TSH in the brain, zebrafish treated with TCEP also had significantly lower T3 and higher T4 levels in their plasma, resulting in a marked decline in the T3/T4 ratio (Figure S2). Since circulating T3, the bioactive form of thyroid hormone, is derived from the peripheral monodeiodination of the outer aromatic ring of T4, the disrupted equilibrium between T3 and T4 (indicated by alterations in T3 and T4 as well as a reduction in the T3/T4 ratio) suggests evidence of HPT-axis dysfunction. ,,, Because the synthesis of thyroid hormones is primarily regulated by TRH and TSH, which are secreted by the hypothalamus and pituitary gland, respectively, the disturbance of T3 and T4 may be due to TCEP-induced suppression of TRH and TSH. , …”

The antibacterials ciprofloxacin, trimethoprim and sulfadiazine modulate gene expression, biomarkers and metabolites associated with stress and growth in gilthead sea bream (Sparus aurata).

“…Alterations in the expression levels of different players of HPT axis, such as trh and tsh, and alterations in zebrafish growth have been documented after exposure to chemical compounds such as perfluorododecanoic acid, naphthoflavone, and benzo[a]pyrene (Movahedinia et al, 2018;Teles et al, 2005a;Zhang et al, 2018), suggesting that the toxicological effect of these compounds could be mediated by HPT axis. In addition, some studies suggest that the modulation of trh transcription is also regulated by concentrations of different thyroid hormones through a negative feedback mechanism (Tan et al, 2022).…”