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Androgens in Congenital Adrenal Hyperplasia.
Front Horm Res 2019; 53:65-76FH

Abstract

Congenital Adrenal Hyperplasias (CAH) are genetic diseases transmitted in an autosomal recessive way and these diseases affect many aspects of human health. The majority of CAH cases is due to a deficiency in 21-hydroxylase as a result of the existence of mutations in both alleles of the CYP21A2 gene. Since the identification of mild, non-classic forms of this disease, CAH has been recognized to be one of the most common genetic diseases in human beings. This disease is generally associated with elevated secretion of androgens, sometimes resulting in virilizing syndromes, including genital ambiguity, precocious puberty in both sexes, or milder syndromes of androgen excess like precocious pubarche or the occurrence of hirsutism and oligomenorrhea in women. Accumulating precursors like 17-hydroxypregnenolone and 17-hydroxyprogesterone (17OHP) are directed to the synthesis of androgens through the enzyme 17-hydroxylase/17,20 lyase leading to the production of dehydroepiandrosterone that is then converted to testosterone and dihydrotestosterone (DHT) at the gonads and at other peripheral tissues. 17OHP, the hallmark of 21-hydroxylase deficiency, can be converted to androstenedione (in a low efficiency molecular process) but can also be converted to DHT through an alternative pathway that becomes active due to the large amounts of accumulated 17OHP - the backdoor pathway. Another important pathway that becomes significant in this disease is the 11-oxyandrogens pathway through which androstenedione is converted to 11β-hydroxyandrostenedione at the adrenal and from there to 11-ketotestosterone and 11-ketoDHT. The elevated androgens levels affect the hypothalamic-pituitary-gonadal axis and, in some cases, the ovary resulting in chronic anovulation and infertility.

Authors+Show Affiliations

Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Porto, Portugal, dpignatelli@yahoo.com. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal, dpignatelli@yahoo.com. Department of Biomedicine, Faculty of Medicine of the University of Porto, Porto, Portugal, dpignatelli@yahoo.com.Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Porto, Portugal. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal. Endocrine, Cardiovascular & Metabolic Research, Department of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto, Porto, Portugal.Alma Mater University of Bologna, Bologna, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31499506

Citation

Pignatelli, Duarte, et al. "Androgens in Congenital Adrenal Hyperplasia." Frontiers of Hormone Research, vol. 53, 2019, pp. 65-76.
Pignatelli D, Pereira SS, Pasquali R. Androgens in Congenital Adrenal Hyperplasia. Front Horm Res. 2019;53:65-76.
Pignatelli, D., Pereira, S. S., & Pasquali, R. (2019). Androgens in Congenital Adrenal Hyperplasia. Frontiers of Hormone Research, 53, pp. 65-76. doi:10.1159/000494903.
Pignatelli D, Pereira SS, Pasquali R. Androgens in Congenital Adrenal Hyperplasia. Front Horm Res. 2019;53:65-76. PubMed PMID: 31499506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Androgens in Congenital Adrenal Hyperplasia. AU - Pignatelli,Duarte, AU - Pereira,Sofia S, AU - Pasquali,Renato, Y1 - 2019/09/09/ PY - 2019/9/10/entrez PY - 2019/9/10/pubmed PY - 2019/9/10/medline SP - 65 EP - 76 JF - Frontiers of hormone research JO - Front Horm Res VL - 53 N2 - Congenital Adrenal Hyperplasias (CAH) are genetic diseases transmitted in an autosomal recessive way and these diseases affect many aspects of human health. The majority of CAH cases is due to a deficiency in 21-hydroxylase as a result of the existence of mutations in both alleles of the CYP21A2 gene. Since the identification of mild, non-classic forms of this disease, CAH has been recognized to be one of the most common genetic diseases in human beings. This disease is generally associated with elevated secretion of androgens, sometimes resulting in virilizing syndromes, including genital ambiguity, precocious puberty in both sexes, or milder syndromes of androgen excess like precocious pubarche or the occurrence of hirsutism and oligomenorrhea in women. Accumulating precursors like 17-hydroxypregnenolone and 17-hydroxyprogesterone (17OHP) are directed to the synthesis of androgens through the enzyme 17-hydroxylase/17,20 lyase leading to the production of dehydroepiandrosterone that is then converted to testosterone and dihydrotestosterone (DHT) at the gonads and at other peripheral tissues. 17OHP, the hallmark of 21-hydroxylase deficiency, can be converted to androstenedione (in a low efficiency molecular process) but can also be converted to DHT through an alternative pathway that becomes active due to the large amounts of accumulated 17OHP - the backdoor pathway. Another important pathway that becomes significant in this disease is the 11-oxyandrogens pathway through which androstenedione is converted to 11β-hydroxyandrostenedione at the adrenal and from there to 11-ketotestosterone and 11-ketoDHT. The elevated androgens levels affect the hypothalamic-pituitary-gonadal axis and, in some cases, the ovary resulting in chronic anovulation and infertility. SN - 1662-3762 UR - https://www.unboundmedicine.com/medline/citation/31499506/Androgens_in_Congenital_Adrenal_Hyperplasia L2 - https://www.karger.com?DOI=10.1159/000494903 DB - PRIME DP - Unbound Medicine ER -