-
European Review For Medical and... Jun 2018We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations... (Review)
Review
OBJECTIVE
We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations causing it.
MATERIALS AND METHODS
We searched PubMed with a larger emphasis on the physiology, genetics and current management of AIS.
RESULTS
AIS is an X-linked recessive Disorder of Sex Development (DSD). It is caused by mutations of the Androgen Receptor, and their large amount and heterogeneity (missense and nonsense mutations, splicing variants, deletions, and insertions) are responsible for the wide spectrum of possible phenotypes of patients, divided into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory investigations have laid the foundation for a diagnostic hypothesis, it is important to identify the actual karyotype of the individual and search for the mutation in the Androgen Receptor to diagnose with certainty the syndrome. Alternatively, in the absence of such evidence, the diagnosis should more properly be an AIS-like condition, which we describe as well in our report.
CONCLUSIONS
The management of this DSD is based on pharmacotherapies, surgery and psychological support: all of them must be directed to facilitate the patient's life, considering his/her sexual identity.
Topics: Androgen-Insensitivity Syndrome; Humans; Male; Mutation; Receptors, Androgen
PubMed: 29949163
DOI: 10.26355/eurrev_201806_15272 -
Lancet (London, England) Oct 2012Androgen insensitivity syndrome in its complete form is a disorder of hormone resistance characterised by a female phenotype in an individual with an XY karyotype and... (Review)
Review
Androgen insensitivity syndrome in its complete form is a disorder of hormone resistance characterised by a female phenotype in an individual with an XY karyotype and testes producing age-appropriate normal concentrations of androgens. Pathogenesis is the result of mutations in the X-linked androgen receptor gene, which encodes for the ligand-activated androgen receptor--a transcription factor and member of the nuclear receptor superfamily. This Seminar describes the clinical manifestations of androgen insensitivity syndrome from infancy to adulthood, reviews the mechanism of androgen action, and shows examples of how mutations of the androgen receptor gene cause the syndrome. Management of androgen insensitivity syndrome should be undertaken by a multidisciplinary team and include gonadectomy to avoid gonad tumours in later life, appropriate sex-hormone replacement at puberty and beyond, and an emphasis on openness in disclosure.
Topics: Androgen-Insensitivity Syndrome; Androgens; Diagnosis, Differential; Female; Humans; Male; Mutation; Zinc Fingers
PubMed: 22698698
DOI: 10.1016/S0140-6736(12)60071-3 -
Archives of Endocrinology and Metabolism 2018Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen... (Review)
Review
Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.
Topics: Androgen-Insensitivity Syndrome; Female; Hormone Replacement Therapy; Humans; Male; Phenotype
PubMed: 29768628
DOI: 10.20945/2359-3997000000031 -
Journal of Neuroendocrinology Feb 2022Widespread sex differences in human brain structure and function have been reported. Research on animal models has demonstrated that sex differences in brain and... (Review)
Review
Widespread sex differences in human brain structure and function have been reported. Research on animal models has demonstrated that sex differences in brain and behavior are induced by steroid hormones during specific, hormone sensitive, developmental periods. It was shown that typical male neural and behavioral characteristics develop under the influence of testosterone, mostly acting during perinatal development. By contrast, typical female neural and behavioral characteristics may actually develop under the influence of estradiol during a specific prepubertal period. This review provides an overview of our current knowledge on the role of steroid hormones in the sexual differentiation of the human brain. Both clinical and neuroimaging data obtained in patients with altered androgen levels/actions (i.e., congenital adrenal hyperplasia or complete androgen insensitivity syndrome [CAIS]), point to an important role of (prenatal) androgens in inducing typical male neural and psychosexual characteristics in humans. In contrast to rodents, there appears to be no obvious role for estrogens in masculinizing the human brain. Furthermore, data from CAIS also suggest a contribution of sex chromosome genes to the development of the human brain. The final part of this review is dedicated to a brief discussion of gender incongruence, also known as gender dysphoria, which has been associated with an altered or less pronounced sexual differentiation of the brain.
Topics: Androgen-Insensitivity Syndrome; Androgens; Animals; Brain; Female; Gonadal Steroid Hormones; Humans; Male; Pregnancy; Sex Differentiation; Steroids
PubMed: 34708466
DOI: 10.1111/jne.13050 -
International Journal of Molecular... Jan 2021Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY... (Review)
Review
Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.
Topics: Androgen-Insensitivity Syndrome; Androgens; Chromosomes, Human, X; Female; Gonads; Hormone Replacement Therapy; Humans; Karyotype; Male; Mutation; Receptors, Androgen
PubMed: 33514065
DOI: 10.3390/ijms22031264 -
Italian Journal of Pediatrics Sep 2021In healthy adolescents, delayed pubarche is generally a benign condition that is caused by a physiological discrepancy between gonadarche and adrenarche. In presence of... (Review)
Review
In healthy adolescents, delayed pubarche is generally a benign condition that is caused by a physiological discrepancy between gonadarche and adrenarche. In presence of other clinical signs and symptoms, delayed pubarche can be caused by single or multiple hormones deficiency (such as adrenal insufficiency, panhypopituitarism and hypothyroidism) and/or genetic conditions (Turner syndrome, androgen insensitivity syndrome). Exposition to endocrine disruptors has also been described as a possible cause of delay of pubic hair development. Basic blood tests, karyotype and first level imaging studies are helpful in the differential diagnosis.
Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Androgen-Insensitivity Syndrome; Endocrine Disruptors; Environmental Exposure; Female; Humans; Hypothyroidism; Male; Puberty, Delayed; Turner Syndrome
PubMed: 34488834
DOI: 10.1186/s13052-021-01134-0 -
Andrology May 2016The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male... (Review)
Review
The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen-AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post-transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post-transcriptional stages.
Topics: Androgen-Insensitivity Syndrome; Androgens; Humans; Male; Muscular Disorders, Atrophic; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Androgen
PubMed: 26991422
DOI: 10.1111/andr.12167 -
Intractable & Rare Diseases Research May 2023Androgen insensitivity syndrome (AIS) is a rare genetic disorder that affects the development of the male reproductive system in individuals with a 46,XY karyotype. In... (Review)
Review
Androgen insensitivity syndrome (AIS) is a rare genetic disorder that affects the development of the male reproductive system in individuals with a 46,XY karyotype. In addition to physical impacts, patients with AIS may face psychological distress and social challenges related to gender identity and acceptance. The major molecular etiology of AIS results from hormone resistance caused by mutations in the X-linked androgen receptor () gene. Depending on the severity of androgen resistance, the wide spectrum of AIS can be divided into complete AIS (CAIS), partial AIS (PAIS), or mild AIS (MAIS). Open issues in the treatment and management of AIS include decisions about reconstructive surgery, genetic counseling, gender assignment, timing of gonadectomy, fertility and physiological outcomes. Although new genomic approaches have improved understanding of the molecular causes of AIS, identification of individuals with AIS can be challenging, and molecular genetic diagnosis is often not achievable. The relationship between AIS genotype and phenotype is not well established. Therefore, the optimal management remains uncertain. The objective of this review is to outline the recent progress and promote understanding of AIS related to the clinical manifestation, molecular genetics and expert multidisciplinary approach, with an emphasis on genetic etiology.
PubMed: 37287652
DOI: 10.5582/irdr.2023.01024