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08.05.2008 | 11:11 AM

Feeding and Metabolism in Mice Lacking Pituitary Adenylate Cyclase-Activating Polypeptide.

Disruption of the pituitary adenylate cyclase-activating polypeptide (PACAP) gene in mice has demonstrated a role for this highly conserved neuropeptide in the regulation of me- tabolism and temperature control. Localization of PACAP neurons within hypothalamic nuclei that regulate appetite suggest PACAP may affect feeding and thus energy balance. We used PACAP-null mice to address this […]

12.04.2008 | 10:00 AM

Reawakened interest for type 3 deiodinase during illness.

Thyroid hormones influence gene expression in virtually all vertebrate tissues. Precise regulation of the active endogenous ligand, 3,5,3′- triiodothyronine (T3), is achieved by the sequential removal of iodine moieties from the thyroid hormone molecule. Type III iodothyronine deiodinase (D3) is the major inactivating enzyme terminating the action of T3 and preventing activation of the prohormone, […]

17.03.2008 | 11:17 AM

Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats.

Thyroid hormone is a critical determinant of cellular metabolism and differentiation. Precise tissue-specific regulation of the active ligand 3,5,3′-triiodothyronine (T3) is achieved by the sequential removal of iodine groups from the thyroid hormone molecule, with type 3 deiodinase (D3) comprising the major inactivating pathway that terminates the action of T3 and prevents activation of the […]

23.11.2007 | 10:38 AM

Reawakened interest in type III iodothyronine deiodinase in critical illness and injury.

Thyroid hormones influence gene expression in virtually all vertebrate tissues. Precise regulation of the active endogenous ligand, 3,5,3′- triiodothyronine (T3), is achieved by the sequential removal of iodine moieties from the thyroid hormone molecule. Type III iodothyronine deiodinase (D3) is the major inactivating enzyme terminating the action of T3 and preventing activation of the prohormone, […]

04.09.2007 | 11:33 AM

Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes.

The Sonic hedgehog (Shh) pathway plays a critical role in hair follicle physiology and is constitutively active in basal cell carcino- mas (BCCs), the most common human malignancy. Type 3 iodo- thyronine deiodinase (D3), the thyroid hormone-inactivating en- zyme, is frequently expressed in proliferating and neoplastic cells, but its role in this context is unknown. […]

27.06.2007 | 10:54 AM

Effects of Rexinoids on Thyrotrope Function and the Hypothalamic-Pituitary-Thyroid Axis.

Retinoid X receptor (RXR)-selective retinoids (rexinoids) can cause central hypothyroidism in humans, and this effect has been confirmed in rodent models. In this report, we charac- terized the effect of rexinoids on the hypothalamic-pituitary- thyroid axis in mice and TSH regulation in a thyrotrope-de- rived cell line. The synthetic rexinoid (LG 268) suppressed TSH and […]

27.06.2007 | 10:21 AM

Atypical Expression of Type 2 Iodothyronine Deiodinase in Thyrotrophs Explains the Thyroxine-Mediated Pituitary Thyrotropin Feedback Mechanism.

Type 2 iodothyronine deiodinase (D2) activates T4 by deiodi- nation to T3, a process being the source of most T3 present in the brain. In the mediobasal hypothalamus, expression of the dio2 gene is potently activated by administration of bacterial lipopolysaccharide (LPS), which in turn mediates the modi- fications in thyroid homeostasis typically observed in […]

17.06.2007 | 11:45 AM

Type 2 iodothyronine deiodinase is highly expressed in germ cells of adult rat testis.

The testis has been classically described as a thyroid hormone unresponsive tissue, but recent studies indicate that these hormones might play an important role in developing testes. We have previously demonstrated that type 2 iodothyronine deiodinase (D2), a thyroid hormone-activating enzyme, is expressed in adult rodent testis and that its activity is induced by hypothyroidism. […]

13.04.2007 | 11:40 AM

Ubiquitination-Induced Conformational Change within the Deiodinase Dimer Is a Switch Regulating Enzyme Activity.

Ubiquitination is a critical posttranslational regulator of protein stability and/or subcellular localization. Here we show that ubiquitination can also regulate proteins by transiently inactivating enzymatic function through conformational change in a dimeric enzyme, which can be reversed upon deubiquitination. Our model system is the thyroid hormone-activating type 2 deiodinase (D2), an endoplasmic reticulum-resident type 1 […]

06.04.2007 | 9:30 AM

Peroxisome Proliferator Activator Receptor Coactivator-1 Expression Is Reduced in Obesity.

Peroxisome proliferator activator receptor- coactivator 1 (PGC-1) is a major candidate gene for diabetes-related meta- bolic phenotypes, contributing to decreased expression of nuclear-encoded mitochondrial genes in muscle and adipose tissue. We have demonstrated that muscle expression of PGC-1 and – is reduced in both genetic (Lepob/Lepob) and acquired obesity (high fat diet). In C57BL6 mice, […]