Expression of Estrogen Receptors in Human Corpus Cavernosum and Male Urethra

Dietrich, Wulf; Haitel, Andrea; Huber, Johannes; Reiter, W

doi:10.1177/002215540405200306

Cited by 62 publications

(56 citation statements)

References 37 publications

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“…On the other hand, the importance of estrogens in male reproductive tract development has been increasingly acknowledged. Functional Estrogen Receptors (ESR)s were detected in differentiating male external genitalia localized at the same structures as the androgen receptors, indicating interactions between effects exerted by the two steroid hormones (7,8); and an excess of estrogens in the developing murine urethra results in an inhibition of the cell proliferation in a dose-dependent manner (9). Moreover, hypospadias has been induced in a mice model by maternal exposure to synthetic estrogens during pregnancy (10).…”

Section: Introductionmentioning

confidence: 99%

Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias

Beleza-Meireles

Töhönen

Söderhäll

et al. 2008

European Journal of Endocrinology

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Introduction: Hypospadias is a common inborn error of the genital development, whose complex etiology remains elusive. Defects of the androgen metabolism and activity have been found in a subset of boys with hypospadias. Moreover, the balance between androgens and estrogens seems to be important to the proper male genital development. Activating transcription factor 3 (ATF3), an estrogen responsive gene, has been reported to be expressed during sexual development and up-regulated in hypospadic genital skin. We investigated ATF3 as a candidate gene for hypospadias. Material and methods: Genotyping of eight-tagged single nucleotide polymorphisms (SNP)s was performed in 330 boys with hypospadias and in 380 healthy controls. Screening for mutations in ATF3 was conducted in a subset of boys with hypospadias. ATF3 expression was evaluated in the foreskin of boys with hypospadias and in healthy controls and in the human fetal genitalia by immunohistochemistry. Results: Three common SNPs, spanning a region of about 16 kb in intron 1 of ATF3, are associated with hypospadias. These SNPs are not linked and their effects are independent. The combination of the three risk SNPs yields the highest significance. Mutation screening identified the gene variant c536AOG in one patient and c817COT in the 3 0 -UTR in two other patients. ATF3 expression was evidenced in the developing male urethra. Conclusions: ATF3 gene variants influence the risk of hypospadias. Its hormonal responsiveness may underlie this risk effect. But also other ATF3-dependent biological aspects, such as cell survival and death, response to stress stimuli, or the control of epithelial-mesenchymal interactions, may be of importance.

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Section: Introductionmentioning

confidence: 99%

Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias

Beleza-Meireles

Töhönen

Söderhäll

et al. 2008

European Journal of Endocrinology

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“…We also found that estrogen and androgen receptors did not have a special side of expression among the prepuce, glans and, urethral plate. Estrogen and androgen receptors are present in developing human fetal penile tissue and both are localized in the same structures of male external genitalia [1,2,4,7,9]. There is also a hormonal balance between androgen and estrogen which exists during the formation of the genital tubercle [1,4,8].…”

Section: Discussionmentioning

confidence: 99%

“…They play an important role during urethral formation of the penile shaft [4,8]. There was expression of estrogen and androgen receptors in the male external genitalia and in developing human fetal penile tissue [1,2,4,7,9]. A higher incidences of hypospadias in the last decade and the demonstration of increased risk of hypospadias in the sons of women exposed to diethylstilbestrol raised questions of the effects of estrogen in the etiology of this defect [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…A higher incidences of hypospadias in the last decade and the demonstration of increased risk of hypospadias in the sons of women exposed to diethylstilbestrol raised questions of the effects of estrogen in the etiology of this defect [5,6]. However, the relevance of estrogen and androgen receptors in the development of the urethra is not yet understood [2,7]. The aim of this study was to investigate the distribution of estrogen and androgen receptors in penile tissues of patients with hypospadias.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Estrogen and Androgen Receptors in Children with Hypospadias: Preliminary Report

Celayır

Eliçevik

Tireli

et al. 2007

Archives of Andrology

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This investigation was conducted to evaluate the presence of estrogen and androgen receptors in penile tissues of patients with hypospadias. The biopsy specimens from prepuce, glans, and urethral plate were sampled during the hypospadias surgery in five patients and were analyzed immunohistochemically. Twelve specimens were investigated for the presence of estrogen or androgen receptors (n: 24); the result was negative in 9 (37%) and positive in 15 (63%). Estrogen receptors were present in 10 specimens (42%) (prepuce: 5, glans: 3, and urethral plate: 2). Androgen receptors were present in 5 specimens (21%) (prepuce: 3, glans: 1, and urethral plate: 1). There was expression of both estrogen and androgen receptors in 5 specimens and only estrogen receptors in the remaining 5. Dominant expression of estrogen receptors in penile tissues of children with hypospadias may be the postnatal finding of disrupted estrogen and androgen receptor interaction during the intrauterine development of external genitalia.

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“…Adding to this complexity then would be the non-genomic mechanisms resulting from cell surface interactions such as excitability of nerve or smooth muscle cell and movement of sodium, potassium and calcium ions; 41 it is to be derived from these views that the oestrogenic tissue response in the males can be mediated in various ways. Together with the pioneering detection of ER-a and ER-b within the cell nuclei of the penile corpus cavernosum, 37,42 it becomes imperative E 2 -T imbalance in ED B Srilatha and PG Adaikan 570 to delineate the individualistic role of these receptors in the context of normal erectile process and in the aetiopathology and pathogenesis of ED.…”

Section: Understanding Oestrogen Effects In the Malementioning

confidence: 99%

Endocrine milieu and erectile dysfunction: is oestradiol–testosterone imbalance, a risk factor in the elderly?

Srilatha

Adaikan²

2011

Asian J Androl

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Oestrogens are not exclusive to the female gender but occur in moderate circulating levels of 25-70 pg ml 21 in men, compared to 44-153 pg ml 21 in women. Arising from aromatisation of testosterone (T), oestrogen is considered to have many opposing physiological functions and the progressive T decline in the aging male is associated with relative and/or absolute increase in serum oestradiol (E 2 ). Sexual disinterest and erectile dysfunction (ED) in the elderly may well be due to pathophysiological E 2 -T imbalance; the altered hormonal ratio may also explain the higher incidence of ED in hyperestrogenism or following exposure to environmental/plant oestrogens. Keywords: aging; erectile dysfunction; hormone imbalance; oestradiol; phytoestrogen; testosterone INTRODUCTIONThe last two decades have witnessed the change in the scientific outlook of erectile dysfunction (ED) which is now regarded as a multifactorial and predominantly an organic disorder. Since the erectile process is a coordinated function with neurologic, vascular, endocrine and ionic inputs, successful therapeutic outcome for ED envisages recognition and delineation of the precipitating causes. An important premise is the increased prevalence of ED with aging 1 coupled with the possibility that the present population of men older than 65 years will double by the year 2025. 2 ED in the elderly is a pertinent clinical issue.Aging is associated with a number of comorbid conditions and risk factors for ED, including central and peripheral nervous system disorders, cardiovascular dysfunctions and side-effect profile of prescription medications. In addition to the wide range of general physical complaints in the elderly, it is imperative to address age-related affective alterations arising possibly from hormonal and lifestyle adjustments. 3 With the multifactorial symptoms and evidence for the missing correlation of testosterone (T) levels in the clinical features of hypogonadism, 4 further complexities have to be considered. For instance, not all aging males present with sexual deterioration and in some, a non-hormonal background to the precipitating conditions affecting sexuality may coexist. These include depression, fragility, decreased vitality, endothelial dysfunction, chronic diseases, cancer, incontinence, cognitive impairment and concurrent problems of the aging partner. At the cellular level too, decreased expression and activation of endothelial nitric oxide (NO) synthase with aging and the subsequent blunting of the physiological actions of NO, may have a non-hormonal basis. Therefore, caution should be used while associating hormonal, particularly oestradiol (E 2 )-T imbalance, to ageassociated ED.Nevertheless, steroid hormone secretion conforms to overall health status in men and understanding the dynamics of endocrine

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Expression of Estrogen Receptors in Human Corpus Cavernosum and Male Urethra

Cited by 62 publications

References 37 publications

Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias

Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias

Expression of Estrogen and Androgen Receptors in Children with Hypospadias: Preliminary Report

Endocrine milieu and erectile dysfunction: is oestradiol–testosterone imbalance, a risk factor in the elderly?

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