Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man.

  title={Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man.},
  author={E P Smith and Jeff Boyd and Graeme R. Frank and H. Takahashi and Robert M. Cohen and Bonny Specker and Timothy C. Williams and Dennis B. Lubahn and Kenneth S. Korach},
  journal={The New England journal of medicine},
  volume={331 16},
BACKGROUND AND METHODS Mutations in the estrogen-receptor gene have been thought to be lethal. A 28-year-old man whose estrogen resistance was caused by a disruptive mutation in the estrogen-receptor gene underwent studies of pituitary-gonadal function and bone density and received transdermal estrogen for six months. Estrogen-receptor DNA, extracted from lymphocytes, was evaluated by analysis of single-strand-conformation polymorphisms and by direct sequencing. RESULTS The patient was tall… 
Genetic mutations resulting in estrogen insufficiency in the male
  • E. Simpson
  • Biology
    Molecular and Cellular Endocrinology
  • 1998
Delayed puberty and estrogen resistance in a woman with estrogen receptor α variant.
An 18-year-old woman without breast development and with markedly elevated serum levels of estrogens and bilateral multicystic ovaries is described, found to have a homozygous loss-of-function ESR1 mutation in a completely conserved residue that interferes with estrogen signaling.
Estrogen receptor mutation in a girl with primary amenorrhea
A 15-year-old girl who presented with primary amenorrhea was reported, showing that disruption of the ER gene is not lethal, and the role of estrogen in bone mineralization and glucose tolerance was emphasized.
Impact of estrogen replacement therapy in a male with congenital aromatase deficiency caused by a novel mutation in the CYP19 gene.
In this rare incidence of estrogen deficiency, estrogen replacement demonstrated its importance for bone mineralization and maturation and glucose metabolism in a male carrying a novel mutation in the CYP19 gene.
Aromatase and estrogen receptor α deficiency.
  • S. Bulun
  • Biology, Medicine
    Fertility and sterility
  • 2014
Familial Multiplicity of Estrogen Insensitivity Associated With a Loss-of-Function ESR1 Mutation
Describing 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.
Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom
  • M. Grumbach
  • Biology, Medicine
    Journal of pediatric endocrinology & metabolism : JPEM
  • 2000
Establishing a role for estrogen does not exclude a direct action of testosterone on bone in the human male (especially on cortical bone), but this action is less characterized than thought in the past and is relatively minor in comparison with the major effect of estrogen in the male.
Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens.
A novel mutation in the CYP19 gene in a sister and brother exhibited the cardinal features of the aromatase deficiency syndrome as recently defined and was reported on.
Estrogen: consequences and implications of human mutations in synthesis and action.
Study of the mutations in CYP19, the gene encoding aromatase, in six females and two males and a mutant estrogen receptor alpha in a man provide illuminating new insights into the critical role of estrogen in the male in the pubertal growth spurt and skeletal maturation, and in the importance of estrogen sufficiency in the accrual and maintenance of bone mass.
Estrogen receptor alpha gene analysis in osteoporosis and familial osteoporosis
Genetic alterations in exons 1 and 2 of ERα are not associated to osteoporosis and familial osteOPorosis, and the codon 10 and codon 87 polymorphisms do not seem to be correlated with BMD and bone turnover markers.


Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.
Prenatal male and female reproductive tract development can occur in the absence of estradiol receptor-mediated responsiveness, and the uteri and vagina do not respond in the animals with the estrogen receptor gene disruption.
Functional characterization of naturally occurring mutant androgen receptors from subjects with complete androgen insensitivity.
This study shows that some cases of CAIS are explained by an inability to form a functional AR-steroid complex and hence, the AR is unable to activate transcription of genes essential for male sex differentiation during fetal development.
Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.
This patient is the first adult to have described the cardinal features of a syndrome of aromatase deficiency, and the results of restriction fragment length polymorphism analysis and direct sequencing of the amplified exon X DNA from the patient's mother indicate maternal inheritance of the R435C mutation.
Genomic organization of the human oestrogen receptor gene.
It is shown that the human ER gene is greater than 140 kb in length, split into eight exons and that the positions of these introns have been highly conserved when compared with the chicken progesterone receptor and are remarkably similar to those of one of the chicken thyroid hormone receptor genes.
Analysis of oncogene alterations in human endometrial carcinoma: Prevalence of ras mutations
The data suggest that the amplification or overexpression of several proto‐oncogenes frequently observed in other human gynecologic and breast tumors are not prevalent in endometrial carcinoma and that ras gene mutations are relatively common in this tumor type.
A comparison of androgen status in patients with prostatic cancer treated with oral and/or parenteral estrogens or by orchidectomy
Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A‐4 and the more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.
Osteopenia in men with a history of delayed puberty.
It is suggested that the timing of puberty is an important determinant of peak bone density in men, and men in whom puberty was delayed may be at increased risk for osteoporotic fractures when they are older.
Osteoporosis and decline of gonadal function in the elderly male.
Like in women, decline of gonadic function determines an increased bone resorption in men too, and a positive linear correlation is evident between PCA and testosterone, androstenedione and estrone plasma levels.
Origin of estrogen in normal men and in women with testicular feminization.
The purpose of this study was to quantify the various sources of estrone (E1) and 17 beta-estradiol (E2) production in normal men and in women with testicular feminization. The mean production rate