Congenital disorders of estrogen biosynthesis and action

Estrogens regulate pubertal development and reproductive function in women, spermatogenesis in men, and bone turnover and metabolic conditions in individuals of both sexes. Estradiol, the major estrogen in humans, is synthesized from testosterone by the action of aromatase and exerts its effects though binding to estrogen receptors. Germline loss- and gain-of-function variants in CYP19A1, the gene encoding aromatase, lead to aromatase deficiency and aromatase excess syndrome, respectively. Germline loss-of-function variants in ESR1, the gene encoding estrogen receptor a, are known to cause of estrogen insensitivity/resistance. In addition, rare variants in ESR1 and ESR2 have been implicated in various disease phenotypes. Clinical studies on these rare endocrine disorders provided clues to understand the biological functions of estrogens in the human body. This review introduces the genetic basis, phenotypes, and current management procedures of congenital disorders in estrogen biosynthesis and action. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Estrogens play important roles in pubertal development, reproductive function, bone turnover, and metabolic conditions. Mutations in genes related to estrogen synthesis and action can lead to congenital disorders. Clinical studies on these disorders provide insights into the functions of estrogens in the human body.