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Cytochrome b₅ Expression in Gonadectomy-induced Adrenocortical Neoplasms of the Domestic Ferret (Mustela putorius furo)

Departments of Pediatrics and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO (SW, MH, DBW), University of Applied Sciences Mannheim, Mannheim, Germany (SW), GlaxoSmithKline, Research Triangle Park, NC (RAP), Department of Pathobiology and Diagnostic Investigation, Michigan State University College of Veterinary Medicine, Lansing, MI (MK), Children's Hospital, Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland (MH)

Abstract

Whereas the adrenal glands of healthy ferrets produce only limited amounts of androgenic steroids, adrenocortical neoplasms that arise in neutered ferrets typically secrete androgens or their derivative, estrogen. The 17,20-lyase activity of cytochrome P450 17-hydroxylase/17,20-lyase (P450c17) must increase to permit androgen biosynthesis in neoplastic adrenal tissue. We screened ferret adrenocortical tumor specimens for expression of cytochrome b₅ (cyt b₅), an allosteric regulator that selectively enhances the 17,20-lyase activity of P450c17. Cyt b₅ immunoreactivity was evident in 24 of 25 (96%) adrenocortical adenomas/carcinomas from ferrets with signs of ectopic sex steroid production. Normal adrenocortical cells lacked cyt b₅, which may account for the low production of adrenal androgens in healthy ferrets. Other markers characteristic of gonadal somatic cells, such as luteinizing hormone receptor, aromatase, and GATA4, were coexpressed with cyt b₅ in some of the tumors. We concluded that cyt b₅ is upregulated during gonadectomy-induced adrenocortical neoplasia and is a marker of androgen synthetic potential in these tumors.

Key words: Adrenal cortex neoplasms; ferrets; luteinizing hormone receptors; Mustelidae; ovariectomy; orchiectomy; steroidogenesis.

Request reprints from Dr. D B Wilson, Department of Pediatrics, Box 8208, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110 (USA). E-mail: wilson_d{at}wustl.edu

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