Aromatase inhibitors in pediatrics

@article{Wit2012AromataseII,
  title={Aromatase inhibitors in pediatrics},
  author={Jan M. Wit and Matti Hero and Susan B. Nunez},
  journal={Nature Reviews Endocrinology},
  year={2012},
  volume={8},
  pages={135-147}
}
Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole… 

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References

SHOWING 1-10 OF 188 REFERENCES

Use of aromatase inhibitors to increase final height

  • L. Dunkel
  • Medicine, Biology
    Molecular and Cellular Endocrinology
  • 2006

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.

History of aromatase: saga of an important biological mediator and therapeutic target.

The saga of these studies of aromatase and the ultimate utilization of inhibitors as highly effective treatments of breast cancer and for use in reproductive disorders serves as the basis for this first Endocrine Reviews history manuscript.

Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene.

Heterozygous inversions in chromosome 15q21.2-3, which caused the coding region of the aromatase gene to lie adjacent to constitutively active cryptic promoters that normally transcribe other genes, resulted in severe estrogen excess owing to the overexpression of aromat enzyme in many tissues.

Aromatase inhibitors in ovulation induction.

An update on the use of aromatase inhibitors for induction of ovulation is presented and several new areas of potential interest are discussed, either alone or together with recombinant follicle-stimulating hormone (FSH) for infertility treatment.

Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment.

This new case of aromatase deficiency confirms previous data on bone maturation and mineralization, and reveals a high risk for the precocious development of cardiovascular disease in young aromat enzyme-deficient men.

The ovarian phenotype of the aromatase knockout (ArKO) mouse

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.

Effect of testosterone and estradiol in a man with aromatase deficiency.

The responses to androgen and estrogen in a man with a novel, homozygous inactivating mutation of cytochrome P-450 aromatase suggest a crucial role of estrogen in skeletal maturation.
...