Testosterone signaling in spermatogenesis, male fertility and infertility
Rajender Singh in Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Androgen insensitivity syndrome (AIS) is a disorder in which there is alteration in the androgen function due to a nonfunctional androgen receptor (AR). This is an X-linked recessive disorder with a 46,XY karyotype. We previously reported a number of mutations in the AR gene that cause AIS (51). Hundreds of such mutations have been tabulated in the Androgen Receptor Gene Mutations Database (52). There are mechanistic studies demonstrating that S-AR−/y mice have defects in the expression of anti-Müllerian hormone, androgen-binding protein, cyclin A1 and sperm-1, which play important roles in the control of spermatogenesis and/or steroidogenesis. Hence, it was shown that Sertoli cell–specific AR knockout mice provide in vivo evidence of the need for functional AR in the Sertoli cells to maintain normal spermatogenesis and testosterone production and to ensure normal male fertility (53). In certain diseases like AIS, spinal bulbar muscular atrophy (SBMA), benign prostatic hyperplasia (BPH) and prostate cancer, abnormalities in the function of androgen receptor have been identified. Recently, novel therapeutic interventions using miRNAs in prostate cancer have been proposed that specifically target the transactivation function of the AR at post-transcriptional stages (54).
EMQ Answers
Justin C. Konje in Complete Revision Guide for MRCOG Part 2, 2019
A Androgen insensitivity syndrome (AIS)Androgen insensitivity syndrome is an intersex condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development. The female patients present at puberty with amenorrhoea with sparse or absent pubic hair. The vaginal is blind ending as there is no uterus/fallopian tubes. The diagnosis is by karyotyping and imaging but ultrasound may confuse a full rectum with a uterus. MRI has a better sensitivity in diagnosis than ultrasound scan.
Scientific Basis of Male Hypogonadism
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Androgen insensitivity syndrome (AIS) is caused by sporadic or familial loss of function mutations of the AR and affects 1 in 20,000 to 90,000 births. More than 600 mutations have been documented in the AR gene, located on Xp11 to 12, 200 in exons B-H carrying steroid and DBDs. Although there are only 23 mutations in exon A, a complete loss of receptor function occurs compared with slight receptor dysfunction in mutations of other exons. The N-terminal section (exon A) of the AR is very variable, containing a polymorphic polyglutamine (CAG) repeat sequences comprising 8 to 35 repeats (Fig. 7). Excess number of CAG repeats (>38) results in androgen resistance because coactivators and androgens bind less strongly to AR with long CAG sequences. The severity of androgen resistance is reflected by the variety of clinical phenotype of affected individuals. Testosterone levels may be within or slightly above the male testosterone reference range with modestly elevated gonadotrophin levels.
New mutation causing androgen insensitivity syndrome – a case report and review of literature
Published in Gynecological Endocrinology, 2019
Marzena Maciejewska-Jeske, Patrycja Rojewska-Madziala, Karolina Broda, Karolina Drabek, Anna Szeliga, Adam Czyzyk, Stanislaw Malinger, Anna Kostrzak, Agnieszka Podfigurna, Gregory Bala, Blazej Meczekalski, Agnieszka Malcher, Maciej Kurpisz
Androgen insensitivity syndrome (AIS), first described by Morris in 1953, is a congenital disorder manifesting as a result of cellular resistance to androgens [1]. The pathogenesis of AIS involves a defect in the androgen receptor gene located on the X chromosome and results in the development of a feminine phenotype in a genetically male (46, XY) individual [2]. Three clinical phenotypes of AIS are observed, relating to the degree of androgen insensitivity: Complete androgen insensitivity syndrome (CAIS) exhibits typical female genitalia, partial androgen insensitivity syndrome (PAIS) is associated with predominantly female or ambiguous genitalia, and mild androgen insensitivity syndrome (MAIS) [2]. PAIS is most often the result of missense mutations in the androgen receptor gene and causes the mildest forms of AIS [3]. In contrast, CAIS manifests as the most complete form of AIS. The female phenotype observed in CAIS is the result of mutations in cellular receptors causing incapacitation and absolute resistance to testosterone and DHT. Primordial testis continues to produce anti-Müllerian hormone, thus suppressing the formation of female internal reproductive organs and leading to primary amenorrhea in adolescence. The lack of androgen stimulation concurrently limits differentiation to proper male external genitalia and virilization [3,4].
Platelet volume indices for the prognosis of acute ischemic stroke patients with intravenous thrombolysis
Published in International Journal of Neuroscience, 2019
Dewei Xie, Weiwei Xiang, Yiyun Weng, Jia Li, Ling Xu, Xu Zhang, Zhibo Chen
We retrospectively collected the information of AIS patients undergoing IVT in the first affiliated hospital of Wenzhou medical university between 2013 and 2016. The diagnosis of AIS was determined by a senior neurologist according to the clinical symptoms, signs and image manifestations. Inclusion criterion included age ≥18 and AIS patients who is undergoing IVT. Exclusion criterion included onset-to-treatment time (OTT) more than 6 hours [13], a stroke history within 3 months, an active inflammatory disease within one week before AIS, malignancy and hematologic diseases and autoimmune diseases. Besides, patients with a baseline mRS score higher than 2, incomplete medical records and a missing 3-month prognostic information were also excluded. Eventully, 183 subjects were eligible for the present study with 42 patients excluded (7 were beyond the therapeutic window, 2 had active inflammatory disease, 13 had incomplete follow-up, 2 had autoimmune diseases and 18 for incomplete medical records). All the patients with a diagnosis of AIS received IVT after informed consent and the study was approved by our ethics committee.
Does exercise therapy improve pulmonary function in patients with Adolescent Idiopathic Scoliosis?
Published in Physiotherapy Theory and Practice, 2023
Anthony Rafferty, Neil Fleming, Patrick Kiely, David Mockler, Sara Dockrell
Studies which satisfied the following criteria were included in the systematic review. 1) Study participants had a clinical diagnosis of AIS; 2) An exercise-based intervention was performed with at least one of the following pulmonary function outcome variables measured pre- and post-intervention: Forced expiredvolume in 1 second (FEV1 or, FEV1%), Forced vital capacity (FVC or FVC%), Vital capacity (VC or VC%), Peak expiratory flow rate (PEF), Total lung capacity (TLC), Maximum expired flow (MEF), Forced inspired volume in 1 second (FIV1), Forced inspiratory vital capacity (FIVC), Peak inspiratory flow rate (PIF), Forced inspiratory flow (FIF), Maximal inspiratory pressure (MIP) or maximal expiratory pressure (MEP); and 3) The study design was a randomized control trial, case-control intervention, or interventional cohort design. Case reports, editorials and literature reviews and studies that included patients with AIS who had cardiorespiratory comorbidities were excluded.
Related Knowledge Centers
- Androgen Receptor
- Disorders of Sex Development
- Karyotype
- Puberty
- Y Chromosome
- Androgen
- Disorders of Sex Development
- Cell
- Development of The Reproductive System
- Secondary Sex Characteristic
- Sex-Determining Region Y Protein