Search

Because the avian thyroid gland secretes almost exclusively thyroxine (T4), the availability of receptor-active 3,3′,5-triiodothyronine (T3) has to be regulated in the extrathyroidal tissues, essentially by deiodination. Like mammals and most other vertebrates, birds possess three types of iodothyronine deiodinases (D1, D2, and D3) that closely resemble their mammalian counterparts, as shown by biochemical characterization studies in several avian species and by cDNA cloning of the three enzymes in chicken. The tissue distribution of these deiodinases has been studied in detail in chicken at the level of activity and mRNA expression. More recently specific antibodies were used to study cellular localization at the protein level. The abundance and distribution of the different deiodinases shows substantial variation during embryonic development and postnatal life. Deiodination in birds is subject to regulation by hormones from several endocrine axes, including thyroid hormones, growth hormone and glucocorticoids. In addition, deiodination is also influenced by external parameters, such as nutrition, temperature, light and also a number of environmental pollutants. The balance between the outer and inner ring deiodination resulting from the impact of all these factors ultimately controls T3availability.

In this paper we report the cloning of the chicken preprothyrotropin-releasing hormone (TRH) cDNA and the study of its hypothalamic distribution. Chicken pre-proTRH contains five exact copies of the TRH progenitor sequence (Glu-His-Pro-Gly) of which only four are flanked by pairs of basic amino acids. In addition, the amino acid sequence contains three sequences that resemble the TRH progenitor sequence but seem to have lost their TRH-coding function during vertebrate evolution. The amino acid sequence homology of preproTRH between different species is very low. Nevertheless, when the tertiary structures are compared using hydrophobicity plots, the resemblance between chicken and rat prepro-TRH is striking. The cloning results also showed that the chicken preproTRH sequence includes neither a rat peptide spacer 4 (Ps4) nor a Ps5 connecting peptide. Comparison of the cDNA sequence with the chicken genome database revealed the presence of two introns, one in the 5′ untranslated region, and another downstream from the translation start site. This means that the gene structure of chicken preproTRH resembles the gene stucture of this precursor in mammals. Based on the cDNA sequence, digoxigenin-labelled probes were produced to study the distribution of preproTRH in the chicken brain. By means of in situhybridization, preproTRH mRNA was detected in the chicken paraventricular nucleus (PVN) and in the lateral hypothalamus (LHy).

This paper reports the results of in vivoand in vitroexperiments on the feedback effects of corticosterone on the hypothalamo–pituitary–adrenal axis in embryos at day 18 of incubation and in 9-day-old chickens. In vivo, a significant negative feedback was detected on the levels of corticotropin-releasing factor (CRF) precursor (proCRF) mRNA and on the plasma concentration of corticosterone, two hours after a single intravenous injection with 40 μg corticosterone. In contrast, the levels of CRF peptide in the hypothalamic area, the CRF receptor type 1 (CRF-R1) mRNA and pro-opiomelanocortin (POMC) mRNA levels in the pituitary were not affected by the in vivoadministration of corticosterone. In vitro, incubation with 1 μM corticosterone did not affect the CRF-R1 mRNA levels in the pituitary, but significant feedback inhibition was observed on the POMC mRNA levels. These in vitroeffects were the same at the two ages studied. The in vitrofeedback effect on the proCRF gene expression, however, differed with age. In 9-day-old animals a decrease in gene expression was observed which was not detectable in embryonic tissue at day 18 of the ontogeny.

Fasting and refeeding have considerable effects on thyroid hormone metabolism. In the present study, 8-day-old meat-type cockerels were subjected to a 2-day starvation period followed by 3 days' refeeding. Blood and tissue samples were collected at the start of the experiment, at 4, 24, and 48 h of starvation, and at 4, 8, 24, 48, and 72 h of refeeding. This study demonstrates that in chicken, fasting decreased plasma T3and TSH levels and increased plasma T4concentrations. This was accompanied by increased hepatic type III deiodinase (D3) and decreased renal D3 activity. There were no changes in hepatic or renal type I deiodinase (D1). Refeeding restored normal plasma T3, T4, and TSH levels, while hepatic D3 and renal D3 activities returned to prefasting levels. Again hepatic D1 was not affected, but renal D1 was lower than the ad libitumvalues during the entire refeeding period. These results confirm that liver D3 is involved in the regulation of plasma T3during fasting and refeeding in the chicken. Northern blot analysis demonstrated increased hepatic D3 mRNA levels during the first day of starvation that disappeared by the end of the second day; refeeding had no additional effects. These results suggest that in fasted chickens the rapid upregulation of hepatic D3 occurs predominantly at a pretranslational level, whereas the drop in hepatic D3 activity after refeeding is probably regulated at a posttranslational level. In addition, renal D3 may play a role in the regulation of local T3availability.

Enzymes catalyzing the outer ring deiodination (ORD) of iodothyronines are important for the regulation of thyroid hormone bioactivity. We have studied ORD of thyroxine (T4) and 3,3',5'-triiodothyronine (rT3) in liver and kidney microsomes offish, i.e. tilapia ( Oreochromis niloticus). Tilapia kidney contains an enzyme which resembles the mammalian selenoenzyme type I iodothyronine deiodinase (ID-I) with respect to substrate preference (rT3 > T4) and high (≈ μM) Kmvalues, but is much less sensitive to selenocysteine (Sec)-targeted inhibitors, including 6-propyl-2-thiouracil (PTU). In contrast, tilapia liver contains an enzyme very similar to mammalian type II deiodinase (ID-II) with respect to substrate preference (T4 > rT3), low (≈ nM) Kmvalues, and lack of sensitivity to Sec inhibitors.

Enzymes catalyzing the outer ring deiodination (ORD) of iodothyronines are important for the regulation of thyroid hormone bioactivity. We have studied ORD of thyroxine (T4) and 3,3',5'‐triiodothyronine (rT3) in liver and kidney microsomes offish, i.e. tilapia (Oreochromis niloticus). Tilapia kidney contains an enzyme which resembles the mammalian selenoenzyme type I iodothyronine deiodinase (ID‐I) with respect to substrate preference (rT3 > T4) and high (≈ μM) Kmvalues, but is much less sensitive to selenocysteine (Sec)‐targeted inhibitors, including 6‐propyl‐2‐thiouracil (PTU). In contrast, tilapia liver contains an enzyme very similar to mammalian type II deiodinase (ID‐II) with respect to substrate preference (T4 > rT3), low (≈ nM) Kmvalues, and lack of sensitivity to Sec inhibitors.

Chickens were used as a model to further analyze the efficacy and specificity of L-692,429, a novel nonpeptidyl mimic of growth hormone (GH)-releasing peptide-6 (GHRP-6), which is a specific GH-releasing secretagogue in mammals. Actions at the level of the pituitary and the hypothalamus were studied. Pituitaries isolated from 1-day-old (C1) chicks responded in a dose-dependent manner to L-692,429 (ED50=10 nM). Using equimolar concentrations of thyrotropin-releasing hormone (TRH), human GH-releasing hormone (hGHRH1–29), and L-692,429 (10 nM), L-692,429 had 20–25% thein vitropotency of the two endogenous releasing factors. There was an additive effect between hGHRH1–29(10 nM) and L-692,429 (10 or 100 nM) on GH release from C1 pituitaries but no such additive effect was observed when pituitaries were exposed to both TRH (10 nM) and L-692,429 (100 nM). An acute challenge with 50 μg L-692,429 resulted in increased plasma GH levels within 5 min, which remained elevated for up to 15 min (C1 chickens). This increase in GH was accompanied by a drop in hypothalamic TRH content by 5 min. Hypothalamic somatostatin (SRIH) content did not change. Plasma corticosterone concentrations were increased following L-692,429 treatment, whereas plasma α-subunit, T4, and T3levels were unchanged. To confirm the role of the decreased hypothalamic TRH concentrations in the GH-releasing activity of L-692,429 in the chicken, chickens (C1) were pretreated with normal rabbit serum (NRS) or a TRH antiserum (1/50) 1 h prior to the L-692,429 challenge. Both groups showed an increase in circulating GH but the increase was within 5 min inhibited by the TRH antiserum pretreatment, whereas no differences were noted in plasma corticosterone levels. It is concluded that in the chicken the GH secretagogue L-692,429 has a dual action site: (1) directly at the level of the pituitary and (2) centrally through an increase in hypothalamic TRH release.

SYNOPSIS. Considering thyroid hormone levels in the chicken, we should keep in mind that these concentrations are the integrated result of production and release on one hand and elimination, tissue utilization or peripheral interconversion on the other. Moreover all these processes can be and are probably influenced by the relative amounts of thyroxine (T4), triiodothyronine (T4) and reverse-triiodothyronine (rT4) as well as by the ratio of free/bound thyroid hormones. Additionally, other hormones will act upon the thyroid axis and its peripheral metabolism and vice versa. Environmental factors directly or indirectly modify or modulate this already complicated picture. In this review, we therefore will first mention the circulating thyroid hormone levels and the thyroid content of iodohormones. In the second section, the control by the central axis of thyroxine production by the thyroid gland as well as some aspects of peripheral metabolism, with the attention focussed on thyroxine monodeiodination is discussed. Processes which are known to be of importance in thyroid physiology such as recompartementalization or bile excretion are hardly studied in avian species. Many questions about the control of thyroid functioning remain unanswered because of the lack of a homologous TSH radioimmunoassay. It is tempting to assume that the mammalian model can give us the answers; however, too many exceptions in regard to thyroid hormone physiology as it is known in mammals are described, thereby underscoring that thyroid physiology in avians should be investigated without a bias towards research done in mammals.