19-hydroxy Steroids in the Aromatase Reaction: Review on Expression and Potential Functions

Scientific evidence related to the aromatase reaction in various biological processes spanning from mid-1960 to today is abundant; however, as our analytical sensitivity increases, a new look at the old chemical reaction is necessary. Here, we review an irreversible aromatase reaction from the substrate androstenedione. It proceeds in 3 consecutive steps. In the first 2 steps, 19-hydroxy steroids are produced. In the third step, estrone is produced. They can dissociate from the enzyme complex and either accumulate in tissues or enter the blood. In this review, we want to highlight the potential importance of these 19-hydroxy steroids in various physiological and pathological conditions. We focus primarily on 19-hydroxy steroids, and in particular on the 19-hydroxyandrostenedione produced by the incomplete aromatase reaction. Using a PubMed database and the search term "aromatase reaction," 19-hydroxylation of androgens and steroid measurements, we detail the chemistry of the aromatase reaction and list previous and current methods used to measure 19-hydroxy steroids. We present evidence of the existence of 19-hydroxy steroids in brain tissue, ovaries, testes, adrenal glands, prostate cancer, as well as during pregnancy and parturition and in Cushing's disease. Based on the available literature, a potential involvement of 19-hydroxy steroids in the brain differentiation process, sperm motility, ovarian function, and hypertension is suggested and warrants future research. We hope that with the advancement of highly specific and sensitive analytical methods, future research into 19-hydroxy steroids will be encouraged, as much remains to be learned and discovered.