Testicular Position in the Androgen Insensitivity Syndrome: Implications for the Role of Androgens in Testicular Descent

Barthold, Julia Spencer; KUMASI-RIVERS, KANDIS; Upadhyay, Jyoti; Shekarriz, Bijan; Imperato‐McGinley, Julianne

doi:10.1016/s0022-5347(05)67411-3

Cited by 66 publications

(20 citation statements)

References 25 publications

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“…Because both mutations are found in androgen insensitivity (reviewed in Ref. 40), these results argue that this medical condition may arise from a defect in the N-to-C interaction of AR. In view of this, the c-Jun-positive effect on hAR N-to-C interaction is likely to be physiologically relevant and responsible for the c-Jun enhancement of hAR transactivation.…”

Section: Discussionmentioning

confidence: 93%

c-Jun Potentiates the Functional Interaction between the Amino and Carboxyl Termini of the Androgen Receptor

Bubulya¹,

Chen²,

Fisher

et al. 2001

Journal of Biological Chemistry

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The transactivation functions of the human androgen receptor (hAR) are regulated by several accessory factors that can be either positive or negative. One factor that has been previously shown to mediate hAR transactivation is the proto-oncoprotein c-Jun. The positive effect is a primary one, can be exerted by both endogenous and exogenous c-Jun, and requires multiple regions of c-Jun. However, the exact mechanism by which c-Jun exerts its enhancing function is unknown. In this study, we have used a mammalian two-hybrid system to ask if c-Jun influences the ligand-dependent amino-to carboxyl-terminal (N-to-C) interaction of hAR, which is thought to be responsible for the homodimerization of this receptor. Our results show that c-Jun enhances both hAR N-to-C terminal interaction and DNA binding in vitro. We have also tested a panel of c-Jun and c-Fos mutants for their activities on the N-to-C interaction, and the data demonstrate that the activities of these mutants parallel their activities on hAR transactivation. A mutation in the hAR activation function-2 (AF-2) abrogates N-to-C interaction, DNA binding, and transactivation, and these activities are not rescued by exogenous c-Jun. Interestingly, the p160 coactivator TIF2 can stimulate hAR N-to-C interaction, a finding consistent with the effect on hAR transactivation. These data strongly suggest that the hAR N-to-C interaction is the target of c-Jun action, and this activity requires a functional receptor AF-2.

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Section: Discussionmentioning

confidence: 93%

c-Jun Potentiates the Functional Interaction between the Amino and Carboxyl Termini of the Androgen Receptor

Bubulya¹,

Chen²,

Fisher

et al. 2001

Journal of Biological Chemistry

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“…This is well exemplified by the role of the androgen receptor (AR) 1 in male sexual development, which is disrupted in males with androgen insensitivity syndrome (for review, see Ref. 1).…”

mentioning

confidence: 99%

p53 Represses Androgen-induced Transactivation of Prostate-specific Antigen by Disrupting hAR Amino- to Carboxyl-terminal Interaction

Shenk

Fisher

Chen

et al. 2001

Journal of Biological Chemistry

106

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Prostate-specific antigen (PSA) is highly overexpressed in prostate cancer. One important regulator of PSA expression is the androgen receptor (AR), the nuclear receptor that mediates the biological actions of androgens. AR is able to up-regulate PSA expression by directly binding and activating the promoter of this gene. We provide evidence here that that this AR activity is repressed by the tumor suppressor protein p53. p53 appears to exert its inhibition of human AR (hAR) by disrupting its amino-to carboxyl-terminal (N-to-C) interaction, which is thought to be responsible for the homodimerization of this receptor. Consistent with this, p53 is also able to block hAR DNA binding in vitro. Our previous data have shown that c-Jun can mediate hAR transactivation, and this appears to result from a positive effect on hAR N-to-C interaction and DNA binding. Interestingly, c-Jun is able to relieve the negative effects of p53 on hAR transactivation, N-to-C interaction, and DNA binding, demonstrating antagonistic activities of these two proteins. Importantly, a p53 mutation found in metastatic prostate cancer severely disrupts the p53 negative activity on hAR, suggesting that the inability of p53 mutants to down-regulate hAR is, in part, responsible for the metastatic phenotype.

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“…One study showed that out of 52 patients with the CAIS diagnosed, 35 (67%) had abdominal, 16 had inguinal, and one had labial testes. [8] The main differential diagnosis for CAIS are complete gonadal dysgenesis (Swyer syndrome) which is distinguished by poor breast development, short stature, and true hermaphrodism which can be differentiated by some degree of masculinization, presence of ovarian tissue on histology specimen.…”

Section: Discussionmentioning

confidence: 99%

Complete androgen insensitivity syndrome: An uncommon presentation with acute abdomen

Hanmayyagari¹,

Guntaka²,

Muppidi³

et al. 2012

J Acad Med Sci

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uterus and only a partially formed vagina, and pubic and axillary hair is scant or absent. The increased testosterone production is secondary to increase in serum luteinizing hormone (LH) concentrations resulting from resistance to the feedback effect of androgens on LH secretion at the hypothalamic-pituitary level. Both the frequency and amplitude of pulses of LH secretion are increased. [6] Serum follicle stimulating hormone (FSH) concentrations are usually normal.We hereby submit a rare presentation of CAIS with acute abdomen due to torsion of intra-abdominal testis which required laparoscopic gonadectomy. Simultaneously, the rarity of such presentation and timing of removal of in situ gonad is also discussed. CASE REPORTA 17-year-old phenotypic female with history of primary amenorrhea, presented to the gynecologist with sudden onset of severe right lower quadrant abdominal pain for 1 day [ Figure 1]. The pain was not associated with any bowel or urinary symptoms. Examination revealed tenderness and guarding over the left lower quadrant of the abdomen. The rest of the abdomen was soft and non-tender. Urgent ultrasound examination was performed. The provisional diagnosis of torsion of the right ovary was made, with uterus not being visualized. Emergency laparoscopic gonadectomy was carried out and the surgeon too noted absence of uterus. Postoperatively, the patient made a satisfactory recovery AbsTRACT CAsE REPORT Access this article online Quick Response Code: Website:www.e-jams.org

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Testicular Position in the Androgen Insensitivity Syndrome: Implications for the Role of Androgens in Testicular Descent

Cited by 66 publications

References 25 publications

c-Jun Potentiates the Functional Interaction between the Amino and Carboxyl Termini of the Androgen Receptor

c-Jun Potentiates the Functional Interaction between the Amino and Carboxyl Termini of the Androgen Receptor

p53 Represses Androgen-induced Transactivation of Prostate-specific Antigen by Disrupting hAR Amino- to Carboxyl-terminal Interaction

Complete androgen insensitivity syndrome: An uncommon presentation with acute abdomen

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