Familial Multiplicity of Estrogen Insensitivity Associated with a Loss-of-Function <i>ESR1</i> Mutation

Bernard, Valérie; Kherra, Sakina; Francou, Bruno; Fagart, Jérôme; Viengchareun, Say; Guéchot, Jérôme; Ladjouze, Asmahane; Guiochon‐Mantel, Anne; Korach, Kenneth S.; Binart, Nadine; Lombès, Marc; Christin-Maître, Sophie

doi:10.1210/jc.2016-2749

Cited by 33 publications

(45 citation statements)

References 23 publications

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“…The first man, at age 28 years, had descended testes of normal volume and normal sperm count with a minor reduction in sperm viability (35). The second man, at age 18 years, had a cryptorchid right testis, hypoplastic left testis and primary hypogonadism, but no semen analysis was reported (36).…”

Section: Spermatogenesismentioning

confidence: 99%

“…Cortical thickness and trabecular volume were reduced. The second man had an undescended right and hypoplastic left testis, low serum testosterone and delayed bone age, but bone mineral density (BMD) data were not reported (36). Interestingly the best characterized man with nonfunctional ERα (89) had a low bone remodeling state, which is in contrast to the high bone remodeling seen in men with congenital aromatase deficiency (40) and hypogonadism (90,91).…”

Section: E2 Linear Bone Growth Cessation Of Growth and Achievement mentioning

confidence: 99%

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MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone

Russell

Grossmann

2019

European Journal of Endocrinology

108

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Evidence has been accumulating that, in men, some of the biological actions traditionally attributed to testosterone acting via the androgen receptor may in fact be dependent on its aromatization to estradiol (E2). In men, E2 circulates at concentrations exceeding those of postmenopausal women, and estrogen receptors are expressed in many male reproductive and somatic tissues. Human studies contributing evidence for the role of E2 in men comprise rare case reports of men lacking aromatase or a functional estrogen receptor alpha, short-term experiments manipulating sex steroid milieu in healthy men, men with organic hypogonadism or men with prostate cancer treated with androgen deprivation therapy (ADT) and from observational studies in community-dwelling men. The collective evidence suggests that, in men, E2 is an important hormone for hypothalamic–pituitary–testicular axis regulation, reproductive function, growth hormone insulin-like growth factor-1 axis regulation, bone growth and maintenance of skeletal health, body composition and glucose metabolism and vasomotor stability. In other tissues, particularly brain, elucidation of the clinical relevance of E2 actions requires further research. From a clinical perspective, the current evidence supports the use of testosterone as the treatment of choice in male hypogonadism, rather than aromatase inhibitors (which raise testosterone and lower E2), selective androgen receptor modulators and selective estrogen receptor modulators (with insufficiently understood tissue-specific estrogenic effects). Finally, E2 treatment, either as add-back to conventional ADT or as sole mode of ADT could be a useful strategy for men with prostate cancer.

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Section: Spermatogenesismentioning

confidence: 99%

Section: E2 Linear Bone Growth Cessation Of Growth and Achievement mentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone

Russell

Grossmann

2019

European Journal of Endocrinology

108

View full text Add to dashboard Cite

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“…Analysis of ESR1 revealed a homozygous missense variant (p.Gln375His) in the LBD that impaired estrogen responsiveness in cell-based assays. More recently, a description was published of the first known family with estrogen resistance (p.Arg394His) (24).…”

Section: R E V I E W S E R I E S : N U C L E a R R E C E P T O R Smentioning

confidence: 99%

Genetic disorders of nuclear receptors

Achermann¹,

Schwabe²,

Fairall³

et al. 2017

Journal of Clinical Investigation

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Following the first isolation of nuclear receptor (NR) genes, genetic disorders caused by NR gene mutations were initially discovered by a candidate gene approach based on their known roles in endocrine pathways and physiologic processes. Subsequently, the identification of disorders has been informed by phenotypes associated with gene disruption in animal models or by genetic linkage studies. More recently, whole exome sequencing has associated pathogenic genetic variants with unexpected, often multisystem, human phenotypes. To date, defects in 20 of 48 human NR genes have been associated with human disorders, with different mutations mediating phenotypes of varying severity or several distinct conditions being associated with different changes in the same gene. Studies of individuals with deleterious genetic variants can elucidate novel roles of human NRs, validating them as targets for drug development or providing new insights into structure-function relationships. Importantly, human genetic discoveries enable definitive disease diagnosis and can provide opportunities to therapeutically manage affected individuals. Here we review germline changes in human NR genes associated with "monogenic" conditions, including a discussion of the structural basis of mutations that cause distinctive changes in NR function and the molecular mechanisms mediating pathogenesis.

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“…In the literature, so far, only 3 female cases with a loss of function mutation in the estrogen receptor ERα encoded by ERS1 gene have been reported [37, 38]. They had extremely high E2 levels, and because of their estrogen resistance, they all lacked an estrogen-induced growth spurt at time of puberty.…”

Section: Goals Of Hrt In Young Adolescentsmentioning

confidence: 99%

Use of Hormone Replacement in Females with Endocrine Disorders

Christin-Maître¹

2017

Horm Res Paediatr

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Hormone replacement therapy (HRT) is necessary in adolescents with primary ovarian insufficiency (POI) in order to avoid estrogen deficiency. The goal of this minirewiew is to present the different types of estrogens (17β-estradiol, estradiol valerate, ethinyl estradiol, and combined equine estrogens) as well as the different types of progestins available. In order to choose among the different types of HRTs, the features of each regimen are being discussed as well as their risks and their respective benefits. The differences between oral combined contraceptive pills and a dissociated regimen containing estrogen and progestins are emphasized. The different effects of HRTs, mainly on feminization, growth spurt, bone mass as well as cardiovascular risk, and the follow-up of these young patients are presented. HRT in adolescents and young adults with estrogen deficiency is necessary and should be continued until the age of natural menopause. Studies have so far essentially included children or adolescents with Turner syndrome. Therefore, studies on HRT including patients with POI and a normal karyotype are necessary.

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Familial Multiplicity of Estrogen Insensitivity Associated with a Loss-of-Function ESR1 Mutation

Abstract: Description and analysis of this family of patients with mutant ERα provide additional clinical findings toward identification and characterization of what was previously thought to be a highly rare clinical condition.

Cited by 33 publications

References 23 publications

MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone

MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone

Genetic disorders of nuclear receptors

Use of Hormone Replacement in Females with Endocrine Disorders

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