Premature ovarian failure in androgen receptor-deficient mice

Shiina, Hiroko; Μatsumoto, Takahiro; Satō, Takashi; Igarashi, Katsuhide; Miyamoto, Junko; Takemasa, Sayuri; Sakari, Matomo; Takada, Ichiro; Nakamura, Takashi; Metzger, Daniel; Chambon, Pierre; Kanno, Jun; Yoshikawa, Hiroyuki; Kato, Shigeaki

doi:10.1073/pnas.0506736102

Cited by 287 publications

(247 citation statements)

References 47 publications

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“…There is evidence that androgens and their receptor are involved in uterine cell proliferation in rats [26]. Recent studies have further explained the important role of androgen receptor in normal female reproduction as described above [21,24]. So, we hypothesized that it is possible that polymorphisms in this gene may affect normal gene function and it could be associated with RSA.…”

Section: Resultsmentioning

confidence: 93%

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Jahaninejad

Ghasemi

Kalantar

et al. 2013

J Assist Reprod Genet

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Purpose This is a case-control study to determine whether G1733A polymorphism of androgen receptor gene is associated with an increased risk for recurrent spontaneous abortion (RSA). Method A total of 85 women with at least two recurrent spontaneous abortion before 20th week of gestation composed the study group. Subjects were genotyped by the polymerase chain reaction restriction fragment length polymorphism method. Results The observed frequencies of GG, GA and AA genotypes of the G1733A polymorphism were 5.89 %, 82.35 % and 11.76 %, respectively, for the patient group and 71.76 %, 23.51 % and 4.71 %, respectively, for the control group. Allele frequencies of the G1733A polymorphism among patients and controls were 0.47 and 0.84, respectively, for the dominant allele (G) (wild type) and 0.53 and 0.16, respectively, for the A allele (mutant type). Conclusions These results indicated that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.Keywords Recurrent spontaneous abortion . Androgen receptor . Polymorphism . RFLP PCR Recurrent spontaneous abortion (RSA) is a reproductive problem that occurs in women in reproductive age with a frequency of 1 %-3 % [20]. It is defined as two or more repeated pregnancy losses before the 20th week of gestation [14]. The risk of miscarriage is enhanced by a variety of factors including chromosomal abnormalities, uterine abnormalities, hereditary thrombophilia, endocrinologic disorders,-immunologic factors, infections, and nutritional and environmental factors [18,19]. In women with a history of recurrent miscarriage, the risk of miscarriage in a subsequent pregnancy is about 40 % to 50 %. It has a major influence on the wellbeing and psychological status of patients, therefore improved diagnosis and development of treatment strategies is essential [6,16,23]. In the past years, research interest has been focused on the association studies between different genetic polymorphisms and recurrent spontaneous abortion.Androgens are lipophilic hormones with several physiological effects in both sexes [17]. Androgen signaling in female is very important for the differentiation of human endometrial stromal cells into decidual cell; a process is called decidualization that critically controls embryo implantation and placentation [11]. The effect of androgens such as testosterone and dihydrotestosterone mediated by androgen receptor (AR) that is a nuclear receptor [3]. Androgen receptor is widely expressed in female reproductive tissue such as endometrium [1] and binds to a steroid ligand and then is transferred into the nucleus, where it regulates the transcription of androgen-responsive genes [5]. The AR gene is located on the X chromosome between q11 and q12 loci and is composed of eight exons [2] that encode a 110-kd protein that contains an N-terminal transactivation domain, Capsule Our results indicated that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.T. Jahaninejad (*) :

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Section: Resultsmentioning

confidence: 93%

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Jahaninejad

Ghasemi

Kalantar

et al. 2013

J Assist Reprod Genet

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“…These findings suggest that androgens enhance FSH action at an early stage of follicular development, but during the final stages of follicular development they mainly serve as a substrate for estrogen synthesis [36]. Aromatase expression and estradiol levels are normal in the ovaries of androgen receptor knockout mice [40], suggesting that androgens are not crucial for aromatase expression in vivo.…”

Section: A Factors Affecting Aromatase Expression In Granulosa Cellsmentioning

confidence: 92%

Aromatase expression in the ovary: Hormonal and molecular regulation

2008

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Summary-Estrogens are synthesized by the aromatase enzyme encoded by the Cyp19a1 gene, which contains an unusually large regulatory region. In most mammals, aromatase expression is under the control of two distinct promoters a gonad-and a brain-specific promoter. In humans, this gene contains 10 tissue-specific promoters that are alternatively used in various cell types and tumors. Each promoter is regulated by a distinct set of regulatory sequences and transcription factors that bind to these specific sequences. The cAMP/PKA/CREB pathway is considered to be the primary signaling cascade through which the gonad Cyp19 promoter is regulated. Very interestingly, in rat luteal cells, the proximal promoter is not controlled in a cAMP dependent manner. Strikingly, these cells express aromatase at high levels similar to those found in preovulatory follicles, suggesting that alternative and powerful mechanisms control aromatase expression in luteal cells and that the rat corpus luteum represents an important paradigm for understanding alternative controls of the aromatase gene. Here, the molecular and cellular mechanisms controlling the expression of the aromatase gene in granulosa and luteal cells are discussed.

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Section: Ar-induced Genes In Follicular Developmentmentioning

confidence: 99%

“…Kitl was identified using genome-wide microarray analysis of RNA from Ar 1 K/K mice ovaries (Shiina et al 2006). In primary wild-type mice GCs, DHT induced the expression of Kitl (Wu et al 2013), whereas flutamide attenuated the induction (Shiina et al 2006). In addition, androgeninduced transactivation of KITL promoter was observed by a luciferase reporter assay in a tumor GC KGN cell line (Shiina et al 2006).…”

Section: Ar-induced Genes In Follicular Developmentmentioning

confidence: 99%

Androgen actions in the ovary: balance is key

Prizant

Gleicher

Sen

2014

Journal of Endocrinology

114

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For many decades, elevated androgens in women have been associated with poor reproductive health. However, recent studies have shown that androgens play a crucial role in women's fertility. The following review provides an overall perspective about how androgens and androgen receptor-mediated actions regulate normal follicular development, as well as discuss emerging concepts, latest perceptions, and controversies regarding androgen actions and signaling in the ovary.

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Premature ovarian failure in androgen receptor-deficient mice

Cited by 287 publications

References 47 publications

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Aromatase expression in the ovary: Hormonal and molecular regulation

Androgen actions in the ovary: balance is key

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