Aromatization of Androstenedione to Estrone by Human Adipose Tissue in Vitro. Correlation with Adipose Tissue Mass, Age, and Endometrial Neoplasia

Abstract

To explore the relationship between extraglandular estrogen formation and the clinical parameters of age, weight, and endometrial neoplasia, an assay was developed to measure the rate of estrogen formation from androgen precursors in human adipose tissue. The substrate, [³H]androstenedione, was more efficient than [³H]testosterone for the aromatase system in this tissue. The highest rate of conversion of androgen to estrogen occurred in tissue slices rather than in minces or microsomal preparations. The addition of cofactor NADPH was not required for aromatization in slices or minces, probably as a consequence of endogenous production of NADPH by the tissue. [³H]Estrone was the sole estrogenic product identified in incubations when [3H]androstenedione was used as the substrate, whereas [³H]estradiol-17/β was the exclusive estrogen detected when using [³H]testosterone. The rate of [³H]estrone formation from [³H]androstenedione in tissue slices was linear with time of incubation up to 2 h and with tissue mass up to 1.0 g. The optimal temperature for aromatase activity in these tissues was 37 C, and the apparent K_m of adipose tissue aromatase for androstenedione was 0.25 /μM. A method was also developed to measure DNA content in the tissue slices used for incubation. When the conversion rates of [³H]androstenedione to [³H]estrone and DNA content were measured in adipose tissue obtained from the abdominal wall of 48 women, 17 women with and 31 women without endometrial neoplasia, the rate of conversion of androstenedione to estrone per unit mass of adipose tissue (g) correlated significantly with calculated body component mass of adipose tissue as well as with calculated unit cell number (10⁶ cells) present in adipose tissue. There was no correlation with age. Moreover, the mean rate of estrone production in the adipose tissue obtained from women with endometrial hyperplasia or carcinoma was significantly higher than that obtained from equivalent weight women without endometrial neoplasia.