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Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well described for all vertebrates and can be tracked down up to the level of gene expression. Both thyroid hormones and corticosteroids may induce morphological changes leading to metamorphosis climax in the neotenic Mexican axolotl (Ambystoma mexicanum). In a first series of experiments, metamorphosis was induced with an injection of 25 μg T4 on three alternate days as judged by a decrease in body weight and tail height together with complete gill resorption. This injection also resulted in elevated plasma concentrations of T3 and corticosterone. Previous results have indicated that the same dose of dexamethasone (DEX) is ineffective in this regard (Gen. Comp. Endocrinol. 127 (2002) 157). In a second series of experiments low doses of T4 (0.5 μg) or DEX (5 μg) were ineffective to induce morphological changes. However, when these submetamorphic doses were injected together, morphological changes were observed within one week leading to complete metamorphosis. It is concluded that thyroid hormones combined with corticosteroids are essential for metamorphosis in the axolotl and that only high doses of either thyroid hormone or corticosteroid can induce morphological changes when injected separately. [Copyright &y& Elsevier]

Recent research has shown that in the chicken important interactions take place between the adrenal and the thyroidal axis both at the central and the peripheral level. In vivo as well as in vitro experiments showed that ovine corticotropin-releasing hormone (oCRH) clearly increases thyrotropin (TSH) secretion in late embryonic and early posthatch chicks. In vivo experiments in older chickens, however, suggested that this response might disappear at a later stage. Therefore we started to study in detail the ontogeny of the TSH releasing activity of oCRH using the in vitro perifusion technique. Several embryonic stages (E14, E16, and E18) as well as posthatch stages (C1, C8, C22, and adult chickens) were included in the study. We also investigated the possible regulatory role of somatostatin (SRIH) in this specific endocrine function of CRH. The perifusion studies show that CRH stimulated the TSH release at all stages tested. The 10 and 100 nM oCRH doses were almost equally effective at the early embryonic stages while in most posthatch stages the higher oCRH dose was significantly more effective than the lower one. The stimulation factor, representative for the relative increase in TSH secretion following oCRH challenge, was high at early embryonic stages and clearly lower in adult animals. This seemed to be related to an age-dependent increase in basal TSH secretion levels. In both embryonic (E19) and posthatch (C8) chicks a pretreatment of the pituitaries with SRIH lowered the sensitivity of the thyrotropes to an oCRH challenge. This effect was more pronounced in the posthatch chicks compared to the embryos. The results show that CRH is capable of stimulating the TSH secretion during the entire life cycle of the chicken and that SRIH may play an important role in the fine-tuning of this response by lowering the sensitivity of the thyrotropes to CRH. [Copyright &y& Elsevier]

Abstract: We previously described the cloning of the full-length chicken thyrotropin receptor (TSHRa) and two splice variants, lacking exon 3 (TSHRb) or both exons 2 and 3 (TSHRc). Here we report the identification of three novel splice variants of the chicken TSHR, named TSHRd, -e and -f, differing in their C-terminal region and containing unique exonic sequences that are not present in the other TSHR variants. This finding suggests a TSHR gene structure with 13 rather than the previously assumed 10 exons. The three novel exons appear to be chicken-specific, as no equivalents of these exons were found in other vertebrate genomes. Like the full-length receptor, the five TSHR splice variants are most abundantly expressed in thyroid gland. TSHRb, -d, -e and -f mRNA was also present in virtually all extra-thyroidal tissues expressing TSHRa, whereas TSHRc shows a more restricted tissue distribution. Whether these receptor transcripts are translated to functional proteins needs to be verified, but if so, they could be attributed various physiological roles. [Copyright &y& Elsevier]

Abstract: Corticotropin-releasing factor (CRF) is considered to be a main adrenocorticotropin-releasing factor in vertebrates. In non-mammalian species, CRF and related peptides cause the release of thyroid-stimulating hormone (TSH) from the anterior pituitary. The actions of CRF peptides are mediated by two G protein coupled receptors (CRF1 and CRF2) that have different ligand specificities. Using ligands that bind preferentially or selectively to the CRF2 we tested the hypothesis that TSH release by the amphibian pituitary gland is mediated by the CRF2. Injection of frog CRF, urocortin 1 or the CRF2-specific ligand urocortin 3 all produced significant, acute increases (by 2h) in plasma thyroxine concentration in prometamorphic tadpoles. Chronic injections of CRF peptides accelerated tadpole metamorphosis, and the peptides with the highest affinity for the CRF2 (urocortin 1 and sauvagine) had the greatest potency. Ligands selective for the CRF2 (frog urocortin 3, mouse urocortins 2 and 3) all accelerated tadpole metamorphosis. We then tested frog urocortins 1 and 3, mouse urocortin 2 and sauvagine for their TSH-releasing activity using dispersed frog anterior pituitary cells in culture. All of the peptides tested markedly enhanced the release of TSH. Secretagogue-induced TSH release was completely blocked by the general CRF receptor antagonist astressin or the CRF2-specific antagonist antisauvagine-30. Conversely, the type 1 CRF receptor-specific antagonist antalarmin had no effect on TSH secretion. Our results support the hypothesis that CRF-induced TSH release by the amphibian pituitary gland is mediated by the CRF2. [Copyright &y& Elsevier]