Steroidogenesis in a virilizing ovarian tumour

Area of Science:

• Endocrinology
• Steroid Biochemistry
• Oncology

Background:

• Virilizing arrhenoblastoma is a rare ovarian tumor associated with androgen excess.
• Understanding the specific metabolic pathways involved is crucial for explaining tumor-induced virilization.

Purpose of the Study:

• To elucidate the steroidogenic pathways in a virilizing arrhenoblastoma.
• To identify the enzymatic basis for testosterone overproduction and its clinical manifestations.

Main Methods:

• Metabolic study using radiolabeled steroid precursors ([7-3H]pregnenolone, [7-3H]17alpha-hydroxypregnenolone, [4-14C]17alpha-hydroxyprogesterone, [4-14C]testosterone).
• Analysis of enzyme activities, including 3beta-hydroxysteroid dehydrogenase-5-isomerase, lyase, and enzymes involved in testosterone catabolism and aromatization.

Main Results:

• The arrhenoblastoma tissue showed deficient 3beta-hydroxysteroid dehydrogenase-5-isomerase activity but compensated with increased lyase activity, maintaining testosterone production.
• Testosterone accumulation, due to deficiencies in enzymes catabolizing testosterone to 17-ketosteroids and impaired aromatization, likely caused in vivo masculinization.
• The tumor uniquely converted 17alpha-hydroxyprogesterone to 11-deoxycortisol, suggesting an adrenal origin.

Conclusions:

• The study reveals a complex interplay of enzyme activities in arrhenoblastoma leading to androgen excess.
• Impaired testosterone catabolism and aromatization are key factors in the tumor's virilizing effects.
• The suggested adrenal origin may explain the limited capacity for testosterone aromatization.