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Amphibian metamorphosis is an excellent example of hormone-dependent control of development. Thyroid hormones (THs) regulate almost all aspects of metamorphosis, including brain development and larval neuroendocrine function. Sex steroids are also important for early brain function, although little is known about interactions between the two hormonal systems. In the present study, we established brain developmental profiles for thyroid hormone receptors (tralpha and trbeta), deiodinases (dio1, dio2 and dio3), aromatase (cyp19) mRNA and activity, oestrogen receptors (eralpha and erbeta), androgen receptor (ar) and 5alpha-reductases (srd5alpha1 and srd5alpha2) mRNA during Silurana (Xenopus) tropicalis metamorphosis. Real-time reverse transcriptase-polymerase chain reaction analyses revealed that all of the genes were expressed in the brain and for most of the genes expression increased during development, with the exception of dio2, srd5alpha1 and srd5alpha2. The ability of premetamorphic tadpoles to respond to exogenous THs was used to investigate the regulation of TH- and sex steroid-related genes in the brain during development. Exposure of premetamorphic tadpoles to triiodothyronine (T3; 0, 0.5, 5 and 50 nm) for 48 h resulted in concentration-dependent increases in trbeta, dio2, dio3, eralpha and erbeta. Expression of srd5alpha2 showed large increases (six- to 7.5-fold) for all three concentrations of T3. No changes were detected in dio1, ar and cyp19 transcript levels; however, cyp19 activity increased significantly at 50 nm T3. The results obtained suggest that expression of TH-related genes and er during development could be regulated by rising levels of THs, as previously documented in Lithobates (Rana) pipiens. The positive regulation of srd5alpha by T3 in the brain suggests that endogenous TH levels help maintain or control the rate at which srd5alpha mRNA levels decrease as metamorphosis progresses. Finally, we have identified sex steroid-related genes that are responsive to T3, providing additional evidence of crosstalk between THs and sex steroids in the tadpolebrain.
Fig. 1. Brain developmental profiles of thyroid hormone-related genes during Silurana tropicalis metamorphosis and adulthood. Transcript levels of tralpha (a), trbeta (b), dio1 (c), dio2 (d) and dio3 (e) were measured in whole brain from Nieuwkoop and Faber (NF) stage 50 until adulthood. Levels of mRNA are expressed relative to NF 50 and are normalised to RNA content. Results for the reference gene ribosomal protein L8 (rpl8; f) are also presented. Bars represent the mean ± SEM. Different letters indicate statistically significant differences between stages (n = 5â8 pools; P<0.05). Brain samples for NF 66 and adulthood were statistically analysed separately from NF 52â60 samples (for details, see Materials and methods). Main morphological characteristics (i.e. whole body and hind limb diagrams) are included for each NF stage of development. Note that the scales of the y-axis vary between genes. A, adult.
Fig. 2. Brain developmental profiles of sex steroid-related genes during Silurana tropicalis metamorphosis and adulthood. Transcript levels of eralpha (a), cyp19 mRNA and activity (b) erbeta (c), srd5alpha1 (d), ar (e) and srd5alpha2 (f) were measured in whole brains from Nieuwkoop and Faber (NF) stage 50 until adulthood (y-axis on the left). Levels of mRNA are expressed relative to NF 50 and are normalised to RNA content. Enzyme activity for cyp19 (b) was measured from NF 52â66 (y-axis on the right) and is expressed in fmol/h normalised to protein content. Bars represent the mean ± SEM. Different letters indicate statistically significant differences between stages (n = 5â8 pools; P<0.05). Brain samples for NF 66 and adulthood were statistically analysed separately from NF 52 to NF 60 samples (for details, see Materials and methods). Significant differences in enzyme activity levels are indicated by small letters (n = 5â6; P<0.05). Note that the scales of the y-axis vary between genes. A, adult.
Fig. 3. Effects of triiodothyronine (T3) exposure on the expression of thyroid hormone-related genes in Silurana tropicalis premetamorphic tadpoles. Silurana tropicalis (Nieuwkoop and Faber stage 52â54) were exposed to T3 (0, 0.5, 5, 50 nm) for 48 h. Effects of T3 on tralpha and trbeta (a), dio1, dio2 and dio3 (b) and the reference genes rpl8, gapdh and 18S (c) are presented. Data are presented as the fold changes relative to control and are normalised to RNA content (note the broken y-axis for a and b). Bars represent the mean ± SEM. Asterisks represent significant differences from the control group (n = 8 pools; *P<0.05; **P<0.01; ***P<0.001). Note that the scales of the y-axis vary between genes.
Fig. 4. Effects of triiodothyronine (T3) exposure on the expression of sex steroid-related genes in Silurana tropicalis premetamorphic tadpoles. Silurana tropicalis (NF 52â54) were exposed to T3 (0, 0.5, 5, 50 nm) for 48 h. Effects of T3 on eralpha and erbeta (a), cyp19 mRNA and activity (b), srd5alpha1 and srd5alpha2 (c) and ar (d) are presented. Gene expression data (y-axis on the left) are presented as the fold changes relative to control and are normalised to RNA content. Enzyme activity (y-axis on the right; b) is expressed in fmol/h normalised to protein content. Bars represent the mean ± SEM. Asterisks represent significant differences in gene expression levels from the control group (n = 8 pools; *P<0.05; **P<0.01; ***P<0.001). Significant differences in enzyme activity levels are indicated by delta (δ; n = 5; P<0.01) relative to the control group. Note that the scales of the y-axis vary between genes.
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