Dual intracellular pathways in gonadotropin releasing hormone (GnRH) induced desensitization of luteinizing hormone (LH) secretion
| Autor: | Jeffrey C. Sellers, L. Wayne Duck, Jimmy D. Neill, M.Patricia Cassina, Lois C. Musgrove |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cholera Toxin
medicine.medical_specialty Gs alpha subunit Molecular Sequence Data Gonadotropin-releasing hormone Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Gonadotropin-Releasing Hormone chemistry.chemical_compound GTP-Binding Proteins Pituitary Gland Anterior Internal medicine medicine Animals Amino Acid Sequence Phosphorylation General Pharmacology Toxicology and Pharmaceutics Receptor Protein kinase A Cells Cultured Protein Kinase C Protein kinase C Binding Sites Cholera toxin General Medicine Luteinizing Hormone Cyclic AMP-Dependent Protein Kinases Peptide Fragments Rats Enzyme Activation Endocrinology Bucladesine chemistry Phorbol Tetradecanoylphorbol Acetate Receptors LHRH Intracellular |
| Zdroj: | Life Sciences. 64:2215-2223 |
| ISSN: | 0024-3205 |
| Popis: | The mechanisms of GnRH-induced desensitization of LH secretion are poorly understood. Protein kinase C (PKC) and protein kinase A (PKA) desensitize some receptors of the 7-membrane type, and the GnRH receptor has consensus phosphorylation sites for PKC in the first and third intracellular loops, and a site for PKA in the first intracellular loop. In the first set of experiments we determined whether synthetic peptides representing the three intracellular loops of the receptor could be phosphorylated in vitro by purified PKC and PKA. As compared with a model substrate peptide for PKC, the third intracellular loop was phosphorylated 74% and the first intracellular loop 21%; PKA-phosphorylated the first intracellular loop peptide 17% as well as a model peptide substrate. In the second set of experiments, we used phorbol 12-myristate 13 acetate (PMA), an established PKC stimulator, and cholera toxin (CTX), established to activate the Gs protein and presumed to activate PKA, to treat cultured rat pituitary cells followed by LH measurements. Treatment with both drugs severely impaired GnRH-stimulated LH secretion whereas neither drug alone reduced LH secretion. Dibutyryl cAMP did not duplicate the effects of cholera toxin suggesting that the CTX action could not be explained by an increase in cAMP. These results suggest that more than one intracellular signaling pathway requires activation in order to induce desensitization; one pathway involves PKC and the other involves a pathway stimulated by cholera toxin, presumably Gs protein, which does not involve PKA. |
| Databáze: | OpenAIRE |
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