Steroid Content and Synthesis in a Virilizing Luteoma

Abstract

We have examined, for the first time, the steroid content and the biosynthetic pathways of a luteoma of pregnancy that caused virilization in mother and infant. The steroid content of the luteoma measured by gas-liquid chromatography and isotope dilution methods was (μg/g tissue): progesterone 0; androstenedione (Δ) 0.46; dehydroepiandrosterone (DHA) 3.1; DHA sulfate 4.3; testosterone (T) 7.6; T sulfate 0.37. The low level of progesterone and high level of C₁₉O₂ steroids are noteworthy. Progesterone-¹⁴C and 17-hydroxypregnenolone-³H in equimolar concentrations and at a ³H/¹⁴C ratio of 8 were incubated with luteoma tissue slices in duplicate in phosphate buffer for 1 and 3 hr at 37 C. After isolation and purification, the ³H/¹⁴C ratios of the added steroid were: 17-hydroxyprogesterone 5.0; Δ 3.5; 5-androstene-3β,17β-diol>100; T>100. The ratios were the same at 1 and 3 hr. DHA-¹⁴C and DHA sulfate-³H were similarly incubated with luteoma slices. After purification, the ratios were: Δ 1.8; T>18. These studies suggest that: 1) Δ and T were synthesized by relatively independent pathways, the former via Δ⁴-steroids, the latter via a Δ⁵-pathway; 2) the Δ⁵-pathway was the dominant one for T synthesis; 3) androstenediol was a precursor of testosterone in the Δ⁵-pathway; 4) DHA-sulfate was converted to T by a route not involving free DHA. These data are in accord with the suggested origin of this tumor from ovarian stroma.