[Molecular defects in hormone receptors and G proteins in human disorders].
The biological effects of hormones are mediated by plasma membrane and nuclear receptors which transmit extracellular signals to the cytoplasm and nucleus. The mutations in these receptors can affect normal signal transduction with loss-of-function mutations leading to hormone resistance and gain-of-function mutations leading to constitutive activation of signaling pathways. Mutations in plasma membrane are involved in a large number of clinical disorders, including dwarfism, Laron syndrome, congenital hyperthyroidism or hypothyroidism, nephrogenic diabetes insipidus, resistance to TSH, LH, FSH and ACTH, Jansen's metaphyseal chondrodysplasia and autosomal dominant hypoparathyroidism. While, mutations in nuclear receptors are the cause of resistance to glucocorticoid, androgen, estrogen, thyroid hormone and vitamin D. The loss-of-function mutations leading to familial hormone resistance disorders are germ line in origin whereas the gain-of-function mutations leading to constitutively active receptors are somatic. The plasma membrane receptors for those disorders except GH resistance consist of seven spanning-transmembranes which couple with GTP binding (G) protein. Abnormal G protein also exhibits gain and loss of function for hormones, leading to tumors and pseudo-hypoparathyroidism, respectively. This review summarizes molecular defects in hormone receptors and G proteins and their associated clinical features.
Takeda
K
K
Clinical Laboratory Medicine, Kochi Medical School, Nankoku.
Sugiura
T
T
D002462:Cell Membrane / Q000235:genetics; D004700:Endocrine System Diseases / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011956:Receptors, Cell Surface / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D015398:Signal Transduction
D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D019204:GTP-Binding Proteins