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The pituitary glycoprotein hormones thyrotrophin (thyroid-stimulating hormone, TSH), lutrophin (luteinising hormone, LH) and follitrophin (follicle-stimulating hormone, FSH), as well as the placental choriongonadotrophin (human chorionic gonadotrophin, hCG) are composed of a common alpha-subunit and a specific beta-subunit, coupled by noncovalent interactions. Formation of alpha/beta dimers is necessary for their biological function. Mutations and polymorphisms in the genes encoding these hormones are relatively rare, apparently because of their vital role in the regulation of reproductive and metabolic functions. However, a few genetic alterations in these genes have been identified and offer valuable, novel information about the structure-function relationships of the glycoprotein hormones. The purpose of this review is to present the known mutations and polymorphisms of the TSH, LH and FSH subunit genes and describe their functional consequences as causative factors of hypothyroidism and hypogonadism. Because genuinely inactivating TSH and gonadotrophin mutations are extremely rare, they are unlikely to be encountered in clinical practice. However, some of the polymorphisms are relatively common and because they may change the immunoreactivity of the hormone, they may result in aberrant laboratory findings.

hormones

Structure-function relationships of glycoprotein hormones; lessons from mutations and polymorphisms of the thyrotrophin and gonadotrophin subunit genes