Steroid Secretion by Masculinizing and “Feminizing” Hilus Cell Tumors*

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Abstract
The clinical course, histology, and steroid secretion observed in two patients with hilus cell tumors are presented. One patient had signs of virilism and the other had estrogenic signs only. Steroid secretion was examined by measuring peripheral and ovarian venous gradients and pre-and postoperative levels of hormones to explain the profound differences in the biological effects exerted by the neoplasms. In the patient with virilism, the tumor's major secretory product was testosterone (T), and the dominant biosynthetic pathway was pregnenolone (Pe) → 17-hydroxypregnenolone → 17-hydroxyprogesterone → androstenedione (Δ) → T. In the patient with estrogenic signs, the major secretory product was Δ, derived from a similar pathway of pregnenolone → 17-hydroxypregnenolone → 17-hydroxyprogesterone → Δ Circulating estrone and estradiol levels were elevated, but the tumor showed limited aromatase activity, as reflected by 60-to 1500-fold larger peripheral-ovarian venous gradients of Δ and T than estrone and estradiol. The high circulating estrogen levels mainly arose from the peripheral aromatization of the increased secretion of Δ by the tumor. It was concluded that a similar steroidogenic pathway was employed by both tumors. The predominant secretion by the neoplasm of either T or Δ was determined by the presence and the oxidation reduction equilibrium of the 17βdehydrogenase enzyme. The action of this enzyme resulted in profound differences in the biological effects exerted by these tumors.

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