03-08-2008, 03:36 PM
RIGTH FROM E-MEDICINE
McCune-Albright syndrome is the result of a postzygotic somatic mutation in the gene coding for the alpha subunit of the stimulatory G protein (Gsa).
The specific mutations that cause McCune-Albright syndrome occur at a site in the protein that mediates the inactivation of the Gsa subunit. Once activated, the mutated Gs alpha subunit remains activated for a prolonged period despite the absence of hormone stimulation of the receptor. The result is constitutive activation of the Gsa subunit, constant stimulation of adenylyl cyclase, and persistently high levels of intracellular cAMP. In various tissues, increased cAMP levels can mediate mitogenesis and increased cell function. The specific phenotype depends on the cell type containing the mutation.
The classic triad of features in McCune-Albright syndrome, polyostotic fibrous dysplasia, autonomous endocrine function, and café au lait skin pigmentation, can all be explained by activation of the Gsa subunit and increased intracellular cAMP.
Eumelanogenesis (formation of brown/black pigment) normally is stimulated by melanocyte-stimulating hormone (MSH) binding to the MSH receptor, a classic G protein receptor coupled to Gsa. Constitutive activation of the Gsa subunit in melanocytes results in the increase in brown pigmentation characteristic of the café au lait spots seen in the syndrome. Likewise, both the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) receptors are Gsa coupled receptors
McCune-Albright syndrome is the result of a postzygotic somatic mutation in the gene coding for the alpha subunit of the stimulatory G protein (Gsa).
The specific mutations that cause McCune-Albright syndrome occur at a site in the protein that mediates the inactivation of the Gsa subunit. Once activated, the mutated Gs alpha subunit remains activated for a prolonged period despite the absence of hormone stimulation of the receptor. The result is constitutive activation of the Gsa subunit, constant stimulation of adenylyl cyclase, and persistently high levels of intracellular cAMP. In various tissues, increased cAMP levels can mediate mitogenesis and increased cell function. The specific phenotype depends on the cell type containing the mutation.
The classic triad of features in McCune-Albright syndrome, polyostotic fibrous dysplasia, autonomous endocrine function, and café au lait skin pigmentation, can all be explained by activation of the Gsa subunit and increased intracellular cAMP.
Eumelanogenesis (formation of brown/black pigment) normally is stimulated by melanocyte-stimulating hormone (MSH) binding to the MSH receptor, a classic G protein receptor coupled to Gsa. Constitutive activation of the Gsa subunit in melanocytes results in the increase in brown pigmentation characteristic of the café au lait spots seen in the syndrome. Likewise, both the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) receptors are Gsa coupled receptors