Steroid sulfatase

Steroid sulfatase (STS), or steryl-sulfatase (EC 3.1.6.2), formerly known as arylsulfatase C, is a

This enzyme catalyses the following chemical reaction

3β-hydroxyandrost-5-en-17-one 3-sulfate + H₂O ${\displaystyle \rightleftharpoons }$ 3β-hydroxyandrost-5-en-17-one + sulfate

Also acts on some related steryl sulfates.

Function

The protein encoded by this gene catalyzes the conversion of

A congenital deficiency in the enzyme is associated with X-linked ichthyosis, a scaly-skin disease affecting roughly 1 in every 2,000 to 6,000 males.^[7][8] The excessive skin scaling and hyperkeratosis is caused by a lack of breakdown and thus accumulation of cholesterol sulfate, a steroid that stabilizes cell membranes and adds cohesion, in the outer layers of the skin.^[4]

Genetic deletions including STS are associated with an increased risk of developmental and mood disorders (and associated traits), and of atrial fibrillation or atrial flutter in males.^[9] Both steroid sulfatase deficiency and common genetic risk variants within STS may confer increased atrial fibrillation risk.^[10] Cardiac arrhythmia in STS deficiency may be related to abnormal development of the interventricular septum or interatrial septum.^[11] Blood-clotting abnormalities may occur more frequently in males with XLI and female carriers.^[12] Knockdown of STS gene expression in human skin cell cultures affects pathways associated with skin function, brain and heart development, and blood-clotting that may be relevant for explaining the skin condition and increased likelihood of ADHD/autism, cardiac arrhythmias and disorders of hemostasis in XLI.^[13]

Steroid sulfates like DHEA sulfate and estrone sulfate serve as large biologically inert reservoirs for conversion into androgens and estrogens, respectively, and hence are of significance for androgen- and estrogen-dependent conditions like prostate cancer, breast cancer, endometriosis, and others. A number of clinical trials have been performed with inhibitors of the enzyme that have demonstrated clinical benefit, particularly in oncology and so far up to Phase II.^[14] The non-steroidal drug Irosustat has been the most studied to date.

Inhibitors

Inhibitors of STS include irosustat, estrone sulfamate (EMATE), estradiol sulfamate (E2MATE), and danazol.^[15][16] The most potent inhibitors are based around the aryl sulfamate pharmacophore^[17] and it is thought that such compounds irreversibly modify the active site formylglycine residue of steroid sulfatase.^[14]

Names

Steryl-sulfatase is also known as arylsulfatase, steroid sulfatase, sterol sulfatase, dehydroepiandrosterone sulfate sulfatase, arylsulfatase C, steroid 3-sulfatase, steroid sulfate sulfohydrolase, dehydroepiandrosterone sulfatase, pregnenolone sulfatase, phenolic steroid sulfatase, 3-beta-hydroxysteroid sulfate sulfatase, as well as by its systematic name steryl-sulfate sulfohydrolase.^[18][19][20]

See also

• Steroidogenic enzyme
• Steroid sulfotransferase
• Estrogen sulfotransferase

References