The subcellular defects in the androgen insensitivity syndrome

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S396-S402
Author(s):  
W. SWOBODA ◽  
K. HERKNER
Keyword(s):  
Binding Capacity ◽  
Kinetic Method ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Normal Female ◽  
Androgen Insensitivity ◽  
Wide Range ◽  
Group A ◽  
Group B ◽  
Tissue Specimens

ABSTRACT The androgen insensitivity syndrome (AIS) was studied with consideration of the complexity of mechanisms involved on the intracellular level: testosterone (T) and dihydrotestosterone (DHT) receptors and the androgen-5α-reductase (A5R). Five children with "normal" female external genitalia (group A) and three patients with variable forms of ambiguity (group B), ages 1 to 18 years, were studied. Tissue specimens from genital skin were analysed for the Kd- and Nmaxvalues of the cytosolic and nuclear T- and DHT-receptors, as well as for the Km- and Vmax-data of the tissue specific A5R. The enzyme analyses were performed with a kinetic method. Results show that patients from group A mainly lack action of the nuclear DHT receptor, combined with reduces binding capacity in the cytosol. T binding was poor in both, cytosolic and nuclear fractions, respectively. Results of group B proved to be more inhomogenous, ranging from total absence of a DHT receptor to normal binding capacities in the nuclear fractions, accompanied by decreased cytosolic Nmax values for that ligand. T binding was poor in all patients of group B in the cytosolic and nuclear fractions, respectively. A5R was qualitatively normal in all patients examined, except one, but decreased enzyme activities could be observed in a wide range. In summary, the study confirms the complex mechanisms, presenting as AIS clinically. Moreover a close relationship between abnormalities of androgen receptor function and changes in A5R activity could be evaluated, thus confirming the recent theories about intracellular androgen action.

scholarly journals XY female with complete androgen insensitivity syndrome with bilateral inguinal hernia

2021 ◽  
Vol 8 (4) ◽  
pp. 1353
Author(s):  
Aafrin Shabbir Baldiwala ◽  
Vipul C. Lad
Keyword(s):  
Inguinal Hernia ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Primary Amenorrhea ◽  
Normal Female ◽  
Bilateral Inguinal Hernia ◽  
Complete Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Primary Amenorrhoea ◽  
The Individual

The complete androgen insensitivity syndrome (AIS), previously called testicular feminization syndrome, is an X-linked recessive rare disorder. AIS is the most common male pseudohermaphrodite. Patient has 46, XY chromosome and testis. The individual is phenotypically female and genotypically male. Antimullerian hormone is produced by the testis. So, uterus and fallopian tubes do not develop in fetus. The fault lies with androgen receptors which are mutated. Male differentiation of external genitals does not occur. The individuals are reared as girls and the condition is suspected when the individual is evaluated for primary amenorrhea, infertility or when unilateral/bilateral inguinal hernia is diagnosed in girls. This disorder includes a spectrum of changes ranging from male infertility to completely normal female external genitalia in a chromosomally male individual. These cases need proper diagnosis and appropriate management. We report this case for its interesting presentation. The patient is a 23 year old female, presented with bilateral labial swellings and primary amenorrhoea. Subsequent investigations were done which revealed that the patient is a genetically male with absence of female internal genitalia but presence of testes. Proper psychological support was also given to her, which is more important.

scholarly journals Phenotypic Diversity and Testosterone-Induced Normalization of Mutant L712F Androgen Receptor Function in a Kindred with Androgen Insensitivity*

2000 ◽  
Vol 85 (9) ◽  
pp. 3245-3250 ◽  
Author(s):  
Paul-Martin Holterhus ◽  
Gernot H. G. Sinnecker ◽  
Olaf Hiort
Keyword(s):  
Androgen Receptor ◽  
Phenotypic Diversity ◽  
Binding Capacity ◽  
Phenotypic Variability ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Physiological Concentration ◽  
Androgen Insensitivity ◽  
Low Concentrations ◽  
In Trans

Abstract Molecular causes of phenotypic diversity in androgen insensitivity syndrome, occurring even in the same family, have rarely been identified. We report on a family with four affected individuals, three brothers (B1–3) and their uncle, displaying strikingly different external genitalia: B1, ambiguous; B2, severe micropenis; B3, slight micropenis; and uncle, micropenis and penoscrotal hypospadias. All had been assigned a male gender. We detected the same L712F mutation of the androgen receptor (AR) gene in each subject. Methyltrienolone binding on cultured genital skin fibroblasts of B2 suggested moderate impairment of the ligand-binding domain [maximal binding capacity, 38.2 fmol/mg protein (normal); Kd, 0.21 nmol/L; normal range, 0.03–0.13 nmol/L]. In trans-activation assays, the mutant 712F-AR showed considerable deficiency at low concentrations of testosterone (0.01–0.1 nmol/L) or dihydrotestosterone (0.01 nmol/L). Remarkably, this could be fully neutralized by testosterone concentrations greater than 1.0 nmol/L. Hence, the 712F-AR could switch its function from subnormal to normal within the physiological concentration range of testosterone. This was reflected by an excellent response to testosterone therapy in B1, B2, and the uncle. Taking into account the well documented individual and time-dependent variation in testosterone concentration in early fetal development, our observations clearly illustrate the potential impact of varying ligand concentrations for distinct cases of phenotypic variability in androgen insensitivity syndrome.

scholarly journals Complete Androgen Insensitivity Syndrome: A Rare Case of Disorder of Sex Development

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Alfonsa Pizzo ◽  
Antonio Simone Laganà ◽  
Irene Borrielli ◽  
Nella Dugo
Keyword(s):  
Rare Case ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
The Body ◽  
Normal Female ◽  
Complete Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Sex Development ◽  
Androgen Resistance ◽  
Female External Genitalia

Androgen Insensitivity Syndrome (AIS) could be considered as a disease that causes resistance to androgens actions, influencing both the morphogenesis and differentiation of the body structures, and systems in which this hormone exerts its effects. It depends on an X-linked mutations in the Androgen Receptor (AR) gene that express a variety of phenotypes ranging from male infertility to completely normal female external genitalia. The clinical phenotypes of AIS could vary and be classified into three categories, as complete (CAIS), partial (PAIS), and mild (MAIS) forms, according to the severity of androgen resistance. We will describe a case of CAIS in a 16-year-old patient.

A CASE REPORT ON ANDROGEN INSENSITIVITY SYNDROME

2021 ◽  
pp. 1-1
Author(s):  
Farhana Farhana
Keyword(s):  
Case Report ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Ring Closure ◽  
Breast Development ◽  
Normal Female ◽  
Loss Of Function ◽  
Androgen Insensitivity ◽  
History Of ◽  
Relevant Family History

Androgen Insensitivity Syndrome is an X linked disorder resulting in normal masculinization of external genitalia due to loss of function mutation in AR gene. Case Report : A 18 year old female presented with C/O not attaining menarche. Patient gives a history of lack of development of pubic and axillary hair. No history of abnormal breast development,cyclical abdominal pain or excessive weight gain. No relevant family history. O/E No palpable swellings in abdomen or bilateral inguinal region. External genitalia appear like a normal female external genitalia. The patient's karyotyping was done and it is of male genotype. The patient is diagnosed as Complete AIS as the phenotype is female and genetically male. The patient is managed by laparoscopic B/L orchidectomy with B/L deep ring closure.

scholarly journals Unexpected Diagnosis of Complete Androgen Insensitivity Syndrome (CAIS) During Inguinal Hernia Repair in 11-year-old-girl

2021 ◽  
pp. 70-75
Author(s):  
Rayan Khalid ◽  
Alaa M. Siddig ◽  
Abdelrahman A. Abudoam ◽  
Abdel Bagi Alzain ◽  
Imad Fadl-Elmula
Keyword(s):  
Inguinal Hernia ◽  
Hernia Repair ◽  
Inguinal Hernia Repair ◽  
External Genitalia ◽  
Genetic Mutation ◽  
Androgen Insensitivity Syndrome ◽  
Normal Female ◽  
Bilateral Inguinal Hernia ◽  
Complete Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity

Complete Androgen Insensitivity Syndrome (CAIS) is an X-link recessive genetic mutation of androgen receptor (AR) gene leading to complete inability of cell to respond to the androgens. CAIS occurs in 1 out of 20,400 XY live-birth babies, and affects about 1–2% of prepubertal girls that present with an inguinal hernia. Although individuals with CAIS have XY, those with grades 6 and 7 on the Quigley scale are born phenotypically female, without any signs of genital masculinization. Thus, individuals affected by CAIS develop a normal external female phenotype with normal female external genitalia, well-developed breast, absent uterus, and bilateral undescended testicles. The question of CAIS diagnosis does not come forward until the absent menses at the puberty is noted or accidentally during an inguinal hernia repair in a premenarchal girl. The present study reports a case of inguinal hernia repair on 11-year-old girl, which led to unexpected intraoperative notion of CAIS. The diagnostic work-up, genetic counseling, sex assignment, and the need for preoperative CAIS screening in girls with bilateral inguinal hernia are described and discussed. Keywords: DSD, CAIS, bilateral inguinal hernia, gonadectomy

scholarly journals Role of Imaging in the Diagnosis and Management of Complete Androgen Insensitivity Syndrome in Adults

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Marco Nezzo ◽  
Pieter De Visschere ◽  
Guy T'Sjoen ◽  
Steven Weyers ◽  
Geert Villeirs
Keyword(s):  
External Genitalia ◽  
Proximal Part ◽  
Androgen Insensitivity Syndrome ◽  
Primary Amenorrhea ◽  
Normal Female ◽  
Adult Women ◽  
Complete Androgen Insensitivity Syndrome ◽  
Androgen Insensitivity ◽  
Female External Genitalia

Complete androgen insensitivity syndrome is an X-linked recessive androgen receptor disorder characterized by a female phenotype with an XY karyotype. Individuals affected by this syndrome have normal female external genitalia but agenesis of the Müllerian duct derivatives, that is, absence of the Fallopian tubes, uterus, cervix, and the proximal part of the vagina, with presence of endoabdominal, labial, or inguinal testes. The estimated prevalence is between 1 and 5 in 100,000 genetic males. Complete androgen insensitivity syndrome can be diagnosed as a result of mismatch between the prenatal sex prediction and the phenotype at birth, can be detected by chance, or remain undetected until investigations for primary amenorrhea. Imaging can be important both to diagnose the pathology and to localize gonads prior to surgical treatment. In this paper, we present three cases of complete androgen insensitivity syndrome in adult women of 34, 22, and 38 years old.

scholarly journals Immediate vs. delayed toe-to-thumb transfer: Is the infection rate greater?

2019 ◽  
Vol 51 (06) ◽  
pp. 434-439
Author(s):  
Matteo Ornelli ◽  
Giovanni Ruocco ◽  
Juste Kaciulyte ◽  
Lara Lazzaro ◽  
Nicola Felici
Keyword(s):  
Infection Rate ◽  
Infection Rates ◽  
Immediate Reconstruction ◽  
Wide Range ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Toe Transfer ◽  
Delayed Reconstruction ◽  
Reconstruction Group

Abstract Background After loss of a thumb, the big toe is a possible donor site for reconstruction with wrap-around free flap and trimmed-toe transfer techniques. Early reconstructions seem to reduce the risk of post-operative infections, despite several studies that show different infection rates of the recipient site in immediate toe-to-hand transfer. The authors carried out a retrospective analysis of their experience in thumb reconstruction with big toe transfer and evaluated the results achieved with both immediate and delayed reconstructions in terms of infection occurrence. Patients and Methods From 2000 to 2017, patients who presented cut, crush and avulsion injuries in the thumb were selected and 33 toe-to-thumb transfers were performed. Patients were divided into two groups: in group A, patients underwent immediate reconstruction, while in group B delayed reconstructions were performed. The two groups received identical antimicrobial prophylaxis. Reliability of the immediate or delayed reconstruction was compared in terms of flap survival, requirement for a secondary intention healing and, in particular, rate of infection. Results 29 male and 4 female patients were treated. Toe-to-thumb transfers were performed in both groups: in group A, 8 wrap-around free flaps and 4 trimmed toe transfers; in group B, 11 wrap-around and 10 trimmed toe transfers. No flap loss occurred in either groups. No cases of infection were detected in the transferred toes. Conclusion For toe-to-thumb transfer, there are published reports of a wide range of infection rates of the recipient sites. The authors compared their results in terms of infection rate between immediate reconstruction, group A, and delayed reconstruction, group B. Immediate toe-to-thumb transfer showed equal success rates to delayed transfer. No statistically significant difference in risk of infection between the two groups was found. Results showed that the immediate reconstruction was as safe and reliable as the delayed one.

scholarly journals Surface Rendering of External Genitalia of a Fetus at the 32nd Week of Gestation Affected by Partial Androgen Insensitivity Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Vincenzo Mazza ◽  
Emma Bertucci ◽  
Silvia Latella ◽  
Carlotta Cani ◽  
Pierluca Ceccarelli ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
External Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Surface Rendering ◽  
Sry Gene ◽  
Androgen Insensitivity ◽  
4D Ultrasound ◽  
Genital Ambiguity ◽  
Parental Counseling ◽  
Partial Androgen Insensitivity Syndrome

Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial androgen insensitivity syndrome by 3D-4D ultrasound.Methods. To report prenatal diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by 3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the mutation analysis of SRY gene and the 5α-reductase 2 gene (SRD5A2).Results. 3D-4D surface rendering allows the detection of external and internal genital malformations and can address the prenatal diagnosis of PAIS and can exclude associated complications.Conclusions. Prenatal diagnosis of PAIS allows an adequate parental counseling and an early optimal management of the condition, not only for the psychological and social reflections but also for the avoidance of complications and postnatal morbidity due to misdiagnosis or delays in the treatment of the genital ambiguity.

Isozyme variation, morphology, and growth response to temperature in Pythium irregulare

1997 ◽  
Vol 75 (12) ◽  
pp. 2073-2081 ◽  
Author(s):  
D. J. S. Barr ◽  
S. I. Warwick ◽  
N. L. Desaulniers
Keyword(s):  
Growth Rate ◽  
Pythium Ultimum ◽  
Morphological Characters ◽  
Published Data ◽  
Pythium Irregulare ◽  
Analysis Group ◽  
Wide Range ◽  
Pythium Sylvaticum ◽  
Group A ◽  
Group B

Isozyme-based genetic diversity, morphological characters, and growth rate at different temperatures were compared in a worldwide collection of 125 isolates presumed to be Pythium irregulare Buisman. The isozyme data was analysed with previously published data for Pythium ultimum Trow and Pythium sylvaticum Campbell & Hendrix. UPGMA cluster analysis yielded a dendrogram with four distinct groups: P. ultimum, P. sylvaticum, and two for P. irregulare. Putative P. irregulare isolates were separated into 33 multilocus genotypes defined by 11 isozyme loci: group A contained 116 isolates in 25 genotypes, and group B, 8 isolates in 7 genotypes. One genotype with a single isolate was determined as P. sylvaticum. Based on the isozyme analysis, group B was considered a distinct taxonomic entity from group A, but lacked any unique morphological character. There was a wide range in oogonium and oospore sizes among different isolates of P. irregulare, with those in group B generally being larger. Some isolates in group A had well developed oogonial spines, but others were essentially spineless, whereas all those in group B were spineless. Both groups A and B contained isolates with distinctly aplerotic oospores and others with essentially plerotic oospores. Antheridial number and shape were highly variable both within and among isolates in the two groups. Growth rate over a range of temperatures varied among isolates in both groups and was not a reliable taxonomic criterion. The irregular shape of oogonia and, when present, oogonial spines were the only reliable characters for distinguishing P. irregulare isolates from other taxa. Key words: taxonomy, Oomycetes, Pythiaceae, Pythium ultimum, Pythium sylvaticum.

scholarly journals Increase in liver nuclear tri-iodothyronine receptors associated with increased deoxyribonucleic acid by long-term administration of tri-iodothyronine in thyroidectomized rats

1979 ◽  
Vol 184 (1) ◽  
pp. 143-148 ◽  
Author(s):  
Hirotoshi Nakamura ◽  
Satoshi Hamada ◽  
Hiroo Imura
Keyword(s):  
Nuclear Receptors ◽  
Binding Capacity ◽  
Relative Increase ◽  
Control Value ◽  
Glycerophosphate Dehydrogenase ◽  
Small Doses ◽  
Term Administration ◽  
Group A ◽  
Group B

The effect of long-term administration of small amounts of tri-iodothyronine was examined on the nuclear tri-iodothyronine receptors in rat liver. The maximal binding capacity (Cmax.) and association constant (Ka) of the receptors were determined in thyroidectomized rats given vehicle alone (group A), 2μg of tri-iodothyronine/100g body wt. (group B) or 7μg of tri-iodothyronine/100g body wt. (group C) for 2 weeks. Scatchard analyses with correction for the amount of endogenous tri-iodothyronine revealed that Cmax. values per g of liver were increased to 1.5 and 2.7 times the control value in groups B and C respectively. Since concentrations of DNA per g of liver were significantly increased in the two groups of hormone-treated rats, Cmax. values per mg of DNA were nearly the same in group B, but still increased significantly in group C compared with group A. Ka values remained unchanged in all three groups of animals. Mitochondrial α-glycerophosphate dehydrogenase activity was 9.6 and 28.7 times as high in groups B and C, respectively, as in group A. Concentrations of endogenous tri-iodothyronine bound to non-histone protein were substantially increased in groups B and C, although concentrations of serum tri-iodothyronine remained rather low. The results obtained indicate that the long-term administration of tri-iodothyronine in small doses induces an increase in the nuclear receptors associated with increased DNA with and without accompanying a relative increase in the receptor concentration in thyroidectomized rats. Also the hormonal effect is closely related to the total number of the nuclear receptors and the concentrations of nuclear tri-iodothyronine bound to the receptors rather than the serum tri-iodothyronine concentrations.

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