Cytochrome b⁵ expression in gonadectomy-induced adrenocortical neoplasms of the domestic ferret (Mustela putorius furo)

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 17α-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 andisa marker of androgen synthetic potential in these tumors.