The influence of stress on thyroid hormone production and peripheral deiodination in the Nile tilapia (Oreochromis niloticus)

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Abstract

The existence of an interaction between the adrenal/interrenal axis and the thyroidal axis has since long been established in vertebrates, including fish. However, in contrast to mammals, birds and amphibians, no effort was made in fish to expand these studies beyond the level of measuring plasma thyroid hormones. We therefore set out to examine the acute effects of a single dose of dexamethasone (DEX) on plasma thyroxine (T4) and 3,5,3′-triiodothyronine (T3) levels, as well as on the activity and mRNA expression of the different iodothyronine deiodinases in liver, gills, kidney and brain in Nile tilapia. To take into account the effect of handling stress, this treatment was compared both to a non-treated and to a saline injected group. In general, the observed changes were acute (3 and 6 h) while values had returned to control levels by 24 h post-injection. Only DEX administration caused an acute drop in circulating T3 levels compared to non-treated animals, while none of the treatments affected plasma T4 levels. This indicates that the DEX induced decrease in plasma T3 levels was not due to a lowered thyroidal hormone production and secretion. DEX injection provoked a decrease in peripheral T3 production capacity via a decrease in hepatic outer ring deiodination activity (both D1 and D2), whereas T3 clearance increased by induction of the inner ring deiodinating D3 pathway in liver and in gills. Deiodination activities in kidney and brain were not affected. Effects of saline injection were only observed in liver, where D1 activity decreased and D3 activity increased as in the DEX group, but to a lesser extent. Real-time PCR showed that the changes in hepatic D3 were clearly regulated at the pretranslational level, while this was not confirmed for the other changes. Our results show that both handling stress and DEX injection acutely disturb peripheral deiodination activity in Nile tilapia. However, the effects of the long acting glucocorticoid analogue are more pronounced and result in a decrease in circulating T3 availability.

Introduction

The primary thyroid hormone (TH) synthesized by the thyroid in teleost fish, as in other vertebrates, is l-thyroxine (T4). Ultimately, most T4 is converted enzymatically to active or inactive derivatives in extrathyroidal tissues. Outer ring deiodination (ORD) removes an iodine from the T4 phenolic ring, thereby creating the receptor-active 3,5,3′-triiodo-l-thyronine (T3). Alternatively, inner ring deiodination (IRD) removes an iodine from the tyrosyl ring to form the receptor-inactive 3,3′, 5′-triiodo-l-thyronine (rT3). T3 itself can be further degraded to inactive 3,3′-diiodo-l-thyronine (T2) through IRD. These ORD and IRD pathways contribute to the regulation of thyroidal status by adjusting T3 availability in plasma and tissues. As in mammals, thyroid hormone deiodination in fish is catalyzed by at least three iodothyronine deiodinases: D1, D2 and D3, that in general have similar biochemical properties as their mammalian counterparts (Byamungu et al., 1990, Leatherland et al., 1990, Mol et al., 1997, Mol et al., 1998, Orozco et al., 2002, Orozco et al., 2003, Sanders et al., 1997, Sanders et al., 1999, Van der Geyten et al., 1998).

Glucocorticoids, predominantly secreted as a response to stress (Harvey et al., 1984), have been demonstrated to affect thyroid function by interacting at both the central and peripheral level in mammals and birds (Decuypere et al., 1983, Kaplan, 1986, Kühn et al., 1998). Stress responses in fish have many similarities to those of other vertebrates (Barton and Iwama, 1991, Wendelaar Bonga, 1997), and thus are probably equally important in regulating thyroid economy in teleost fish. There is, however, surprisingly limited data available concerning the interaction of glucocorticoids with thyroid hormone production and peripheral deiodination in fish. A chronic pharmacological dose of cortisol (50 μg/kg) increased plasma T4 concentrations in rainbow trout (Oncorhynchus mykiss) whereas plasma T3 levels tended to decrease (Milne and Leatherland, 1980). In contrast, Redding and co-workers (1986) demonstrated that a single intravenous injection of cortisol hemisuccinate (15–150 μg/kg) in European eel (Anguilla anguilla) decreased plasma concentrations of T3 and T4 in a dose-dependent manner, without affecting plasma T4 clearance, but increasing plasma T3 clearance. These data suggest that cortisol under these conditions decreased thyroid hormone production and increased T3 degradation. However, in contrast to the above findings, long term (56 days) intraperitoneal implantation of cortisol (50 μg/kg) in a medium of hydrogenated coconut oil had no effect on plasma T4 and T3 concentrations in brook charr (Salvelinus fontinalis), although the T4 to T3 conversion had significantly increased (Vijayan et al., 1988). This discrepancy could only be explained by assuming that under these conditions the clearance of T3 from plasma had increased, which is in agreement with the data obtained in eel (Redding et al., 1986). Intraperitoneal implantation of cortisol (10–25 mg/kg) in hydrogenated corn oil caused a significant decrease in plasma T3 that was again accompanied by an increase in T3 clearance rate in rainbow trout (O. mykiss) without affecting the T4 levels and hepatic monodeiodinase activity, thereby suggesting that chronic physiological levels of cortisol enhance plasma T3 clearance while having no effect on T4 production and hepatic conversion into T3 (Brown et al., 1991).

In summary, all the available data on the effects of glucocorticoids on plasma thyroid hormone levels and peripheral deiodination in fish so far do not allow to formulate any clear cut conclusions. Although it appears that exposure to glucocorticoids tends to decrease plasma T3 levels, changes in plasma T4 levels are more variable. Furthermore, so far, insufficient data are available to allow any speculations about the role of the iodothyronine deiodinases in this scheme. The goal of the present study was therefore to investigate the effects of a single injection of a long acting synthetic glucocorticoid—dexamethasone—on circulating TH levels and on peripheral thyroid hormone metabolism in Nile tilapia (Oreochromis niloticus). To take into account the effect of handling stress, this treatment was compared both to a non-treated and to a saline injected group. The Nile tilapia was chosen as an experimental model, because in the last decade it has become one of the most extensively studied fish species in the field of thyroid physiology, especially when it comes to elucidating the function and regulation of iodothyronine deiodinases in fish (Orozco and Valverde, 2005).

Section snippets

Experimental design

Nile tilapia (O. niloticus) were obtained from a commercial fish farm (Maryn Donkers, Boerdonk, The Netherlands). One hundred and forty fishes with a mean weight of 290 ± 20 g were randomly distributed over seven tanks and were acclimatized for 2 weeks in the laboratory in 200-l white fiberglass tanks supplied with aerated running tap water of 25 ± 0.5 °C (flow rate: 1.1 l/min). Light–dark regime was 12/12 h. The fish were fed ad libitum with commercial tilapia pellets (Tilapia TI-3 feed, Skretting.

Results

Table 2 shows the F and p values of the two-way ANOVA analysis of all parameters for non-treated, saline and DEX injected fish.

Discussion

The present study clearly demonstrates that in Nile tilapia, the administration of 25 μg DEX per 100 g body weight can acutely reduce plasma T3 concentrations. These finding are in agreement with previous studies done in yearling coho salmon (Oncorhynchus kisutch) and European eel (A. anguilla) where cortisol injection decreased plasma T3 levels (Redding et al., 1984, Redding et al., 1986). Similar results were also obtained in rainbow trout (O. mykiss) using cortisol implants (Brown et al., 1991

Acknowledgments

We wish to thank L. Noterdaeme, W. Van Ham and F. Voets for their technical assistance during the experiment. This study was supported by the FWO Grant G.0272.04. C.N. Walpita was supported by an IRO scholarship from the KU Leuven and the Flemish Interuniversity Council (VLIR). Serge Van der Geyten was supported by the Fund for Scientific Research—Flanders. The authors declare that there is no conflict of interests that would prejudice the impartiality of this scientific work.

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