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20 - Androgen insensitivity syndromes

from Part III - Management of specific disorders

Published online by Cambridge University Press:  04 May 2010

By
Jarmo Jääskeläinen  and
Ieuan A. Hughes
Edited by
Adam H. Balen ,
Sarah M. Creighton ,
Melanie C. Davies ,
Jane MacDougall  and
Richard Stanhope
Jarmo Jääskeläinen
Affiliation:
Department of Paediatrics, Addenbrooke's Hospital, Cambridge
Ieuan A. Hughes
Affiliation:
Department of Paediatrics, Addenbrooke's Hospital, Cambridge
Adam H. Balen
Affiliation:
Leeds Teaching Hospitals, University Trust
Sarah M. Creighton
Affiliation:
University College London Hospitals
Melanie C. Davies
Affiliation:
University College London
Jane MacDougall
Affiliation:
Addenbrooke's Hospital, Cambridge
Richard Stanhope
Affiliation:
Great Ormond Street Hospital
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Summary

Introduction

Androgen insensitivity syndromes (AIS) arise from target tissue resistance to androgen action. The clinical manifestations of androgen resistance vary from external genitalia that are completely female to degrees of partial masculinization. These syndromes are the most common identifiable cause of male undermasculinization.

Role of androgens in sex determination

After development of the testis (sex determination), which is not androgen dependent, the events of male sex differentiation involve two pathways, one inhibitory and one stimulatory. The principal function of the inhibitory pathway is to cause regression of the Müllerian ducts and thus to repress the development of female internal genitalia (Fallopian tubes, uterus, and upper third of the vagina). This process occurs between six and eight weeks' gestation, mediated by anti-Müllerian hormone (Josso and Clemente, 2003). The stimulatory events of male sex differentiation require high levels of androgens and a functional androgen receptor (AR). Testosterone is thought to be critical in stabilizing the Wolffian duct system to prevent its involution and to induce differentiation into the epididymides, vasa deferentia and seminal vesicles. Stabilization of the Wolffian ducts occurs between 9 and 13 weeks' gestation, when testosterone is secreted from the testes, mostly under the control of placental chorionic gonadotrophin. Dihydrotestosterone (DHT) cannot be involved in this process, as the 5α-reductase enzyme that converts testosterone into DHT is not yet expressed in these tissues (Wilson et al., 1993).

Type
Chapter
Information
Paediatric and Adolescent Gynaecology
A Multidisciplinary Approach
 , pp. 253 - 266
Publisher: Cambridge University Press
Print publication year: 2004

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