Placenta aromatizing enzyme

The distribution, between the placenta and fetus, of the activity of some of the major enzymes involved in steroid synthesis is shown in Table 2. After birth the lack of 3/3-HSD, the aromatizing enzymes, and sulfotransferases is not compensated for by the placenta, with the result that (a) only relatively small quantities of 3-oxo-A steroids are formed, but despite this, cortisol production is adequate (see Section 7.3) (b) the newborn infant cannot convert its large supply of estrogen precursors to estrogen and (c) it cannot desulfurylate its steroids, which have been sulfated by the considerable and widely distributed activity of sulfotransferases (B24, W3). 

There is evidence [52] that there are at least two forms of cyt P-450 involved with aromatization. Likewise, there is evidence for different aromatases in human placenta which catalyse the production of oestrone and oestriol from 4-androstenedi-one and 16a-hydroxytestosterone, respectively. Each enzyme system has been subfractionated into its own cyt P-450 and cyt P-450 reductase [107]. This has been supported recently by Purohit and Oakey [108], who measured aromatase activity for 16a-hydroxy-4-androstenedione and 4-androstenedione in the presence or absence of the other substrate. 4-Androstenedione competitively inhibited aromatization of the 16a-hydroxy derivative, with apparent K, essentially the same as its apparent Km, suggesting that both substrates bind and are aromatized independently of each other. The 16a-hydroxy derivative competitively inhibited the aromatization of 4-androstenedione, thus presumably lowering the affinity of the aromatase for the latter. 

SULT 2A and 2B sulfotransferase subfamily members sulfate the 3P-hydroxyl group of a variety of steroid hormones. Dehydroepiandrosterone (DHEA) is the prototypical substrate for the SULT 2 enzymes. However, other hydroxysteroids such as testosterone and its phase I hydroxylated derivatives are substrates for these enzymes. The SULT 2 sulfotransferases also are responsible for the sulfate conjugation of a variety of alcohols and xenobiotics that have undergone phase I hydro-xylation, including the polycyclic aromatic hydrocarbons (PAHs). The SULT 2 enzymes exhibit different patterns of tissue expression. SULT 2A1 is expressed primarily in the adrenal cortex, brain, liver, and intestine, while SULT 2B1 is expressed in the prostate, placenta, and trachea. 

According to the information available, then, three enzymes take part in the aromatization of neutral Cig-stcroids. These are a 19-hydroxylase, a 19-oxida.so and an aldehyde lyase (desmolase), and all are to be found in the microsomal fraction of human placenta. 

The over-all aromatization has been investigated by Ryan (1959). Human placental (term) microsomes contain all the enzymes necessary. When supplemented with TPNH and incubated at pH 7.0 in an aerobic atmosphere, a production of estrogen calculated to be approximately 1 mg. per hour for an average 500 gm. placenta can be attained. A pre-... 

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