Related Experiment Videos
[Endocrinology 1998-1999]
1Laborator pro endokrinologii a metabolizmus, III. interní kliniky 1. LF UK a VFN, Praha.
Abstract:
In the cascade hormone--second messenger--cellular G-proteins (GTP binding proteins), impairment can occur also at the last step: Mutant G-proteins may amplify the response (e.g. hypophyseal and thyroid adenomas) or reduce it (pseudohypoparathyreosis, testitoxicosis). Other new group of diseases appears to be anexinopathy: Among anexins belong also lippocortins and impairments occur in the hemocoagulation. "Reverse endocrinology" is a process description when the recognition of receptor (called an "orphan receptor") comes earlier than that of the hormone: Such receptors are known for several steroid hormones, retinoids and eicosanoids and it appears they are important also in the metabolism of cholesterol. A single antigen--glutamic acid decarboxylase (GAD), can cause autoimmune disease as the immuno-dependent diabetes (IDDM). Treatment of the skin T-cell lymphoma by some retinoids can result in hypothyroidism. Retrotransposones are example of the human genome modification with yet unknown clinical manifestations. Hepatocytal growth factor reveals to be the hope for treatment of cirrhosis. Search for effective peroral insulin substitutes is at present based on testing of various metabolites of fungi. Antibodies against TNF (tumor necrosis factor) become tested as "anti-cytokine therapy" in patients with rheumatoid arthritis. Some other suggestions for new ways of treatment is also listed, including the intranasal administration of estradiol.
Insights
Disruptions in G-protein signaling and anexinopathies cause various diseases. Research explores novel treatments for conditions like autoimmune diabetes and rheumatoid arthritis, including hormone and growth factor therapies.
Area of Science:
- Endocrinology and molecular signaling pathways.
- Genetics and human genome modifications.
- Immunology and autoimmune diseases.
Context:
- Explores the final step in the hormone-second messenger-G-protein cascade, where G-protein mutations lead to diseases like adenomas and pseudohypoparathyreosis.
- Introduces anexinopathies, including lippocortins, and their role in hemocoagulation disorders.
- Defines 'reverse endocrinology' where orphan receptors are identified before their corresponding hormones, impacting steroid hormone, retinoid, and eicosanoid signaling, and cholesterol metabolism.
Purpose:
- To review emerging research and potential therapeutic targets in endocrinology and related fields.
- To highlight novel disease mechanisms and treatment strategies.
- To discuss advancements in understanding genetic modifications and autoimmune responses.
Summary:
- Discusses G-protein mutations causing endocrine disorders and anexinopathies affecting hemocoagulation.
- Highlights 'reverse endocrinology' with orphan receptors and their link to steroid hormones, retinoids, and cholesterol.
- Covers autoimmune diabetes (IDDM) linked to glutamic acid decarboxylase (GAD), retinoid effects on thyroid, retrotransposons, hepatocyte growth factor for cirrhosis, fungal metabolites for insulin, anti-TNF therapy for rheumatoid arthritis, and intranasal estradiol administration.
Impact:
- Identifies new disease groups and mechanisms, such as G-proteinopathies and anexinopathies.
- Suggests novel therapeutic avenues including growth factors, anti-cytokine therapy, and alternative drug delivery methods.
- Provides insights into the clinical relevance of orphan receptors and genetic elements like retrotransposons.