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<Structure load='3EQM' size='400' frame='true' align='right' caption='Crystal structure of human placental aromatase cytochrome P450 in complex with androstenedione (PDB entry [http://www.pdb.org/pdb/explore/explore.do?structureId=3EQM])' scene='Insert optional scene name here' /> | <Structure load='3EQM' size='400' frame='true' align='right' caption='Crystal structure of human placental aromatase cytochrome P450 in complex with androstenedione (PDB entry [http://www.pdb.org/pdb/explore/explore.do?structureId=3EQM])' scene='Insert optional scene name here' /> | ||
== Introduction == | == Introduction == | ||
| - | Aromatase belongs to the cytochrome p450 family. During aromatization reactions, Aromatase forms an electron-transfer complex with its partner, NADPH-cytochrome p450 reductase. This enzyme is localized in the endoplasmic reticulum of the cell and tissue specific promoters regulate its activity. | + | Aromatase belongs to the cytochrome p450 family. During aromatization reactions, Aromatase forms an electron-transfer complex with its partner, NADPH-cytochrome p450 reductase. This enzyme is localized in the endoplasmic reticulum of the cell and tissue specific promoters regulate its activity. In a number of species, including humans, aromatase can be found throughout the body in places such as the brain, gonads, blood vessels, endometrium, skin, bone and tissues including the placenta and adipose tissue. <ref> Conley, A., Hinshelwood, M. "Mammalian Aromatases". [http://www.ncbi.nlm.nih.gov/pubmed/11427156] </ref> |
== Function == | == Function == | ||
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Contents |
Aromatase
|
Introduction
Aromatase belongs to the cytochrome p450 family. During aromatization reactions, Aromatase forms an electron-transfer complex with its partner, NADPH-cytochrome p450 reductase. This enzyme is localized in the endoplasmic reticulum of the cell and tissue specific promoters regulate its activity. In a number of species, including humans, aromatase can be found throughout the body in places such as the brain, gonads, blood vessels, endometrium, skin, bone and tissues including the placenta and adipose tissue. [1]
Function
The primary function of Aromatase is to produce estrogens by aromatizing androgens. Aromatase converts androstenedione to estrogen and testosterone to estradiol. [2] Aromatase is also a key enzyme in the biosynthesis of estrogens through a process called steroidogenesis. This enzyme helps produce this female sex hormone, estrogen, that helps to fuel the growth of hormone receptor-positive breast cancer.
Aromatase Inhibitors
Inhibitors of Aromatase stop the estrogen production in post-menopausal women. This action is done by blocking the Aromatase enzyme by turning the hormone, androgen, into small amounts of estrogen. [3] There are three Aromatase Inhibitors that are often used in the treatment of breast cancer:
- Arimidex (Anastrozole)
- Aromasin (Exemestane)
- Femara (Letrozole)
Aromatase Inhibitors are unable to stop ovaries from producing estrogen, therefore, these inhibitors only work in post-menopausal women.
Disorders
- Aromatase Enzyme Deficiency
Aromatase Dificiency is rare in humans, however, if aromatase is nonfunctional due to a mutation estrogen synthesis cannot occur. Affected females are diagnoses at birth because of the obvious characteristics of pseudohermaphroditism. During the childhood of these girls, delayed bone maturation can occur along with cystic ovaries. However, affected males are diagnosed later in life because there are not obvious birth defects. Clincal symptoms such as a tall physique, delayed bone maturation and epiphyseal closure, bone pain, and excess adiposy. [4]
- Aromatase Excess Syndrome
Research shows a rare disorder caused by excessive aromatase activity that can cause familial gynecomastia and feminization of both sexes. This can be inherited by an autosomal dominant manner, affected females and males differently. Females with this disorder showed signs of isosexual precocity and/or macromastia. Males showed characteristics of heterosexual precocity and/or gynecomastia. [5]
References
- ↑ Conley, A., Hinshelwood, M. "Mammalian Aromatases". [1]
- ↑ "Aromatase Products" [2]
- ↑ "Aromatase Inhibitors" [3]
- ↑ Jones, M., Boon, W., McInnes, K. "Recognizing Rare Disorders: Aromatase Deficiency". [4]
- ↑ Stratakis, C., Vottero, A. "The Aromatase Excess Syndrome is Associated with Feminization of Bost Sexes and Autosomal Dominant Transmission of Aberrant p450 Aromatase Gene Transcription. [5]
