Comparison of enzyme-expression in adrenal glands of intact ferrets, ferrets treated with a depot GnRH agonist and surgically castrated ferrets.

Abstract

Hyperadrenocorticism in a common disease in neutered pet ferrets. The disease is characterized by an excessive production of sex steroids: androstenedione, 17α-hydroxyprogesterone and/or estradiol concentrations are increased. The aim of this study was to determine if there are differences in the enzymatic pathways in the adrenal glands of intact ferrets, ferrets treated with depot GnRH agonist (deslorelin) and/or those which were surgically castrated. To achieve this, the expression of the enzymes P450c17, cytochrome b5, P450c21, NAPDH:cytochrome P450 reductase, anti-Müllerian hormone and the luteinizing hormone-receptor were examined in the adrenal glands of 14 male ferrets. Cytochrome b5 is an allosteric regulator and modulates the two activities of P450c17 (17α-hydroxylase and 17,20-lyase). Co-expression of cytochrome b5 and P450c17 is necessary for androgen synthesis. We expected to find this co-expression in adrenocortical neoplasia. We showed that cytochrome b5 is normally present in the ferret adrenal cortex. We also performed a hCG-stimulation test in order to see if the adrenal glands in castrated (hormonal or surgical) ferrets were productive. Only the plasma androgen concentrations of 2 surgically castrated ferrets with an adrenocortical adenoma increased after stimulation with hCG. Our results show that ferrets with a steroid-producing adrenocortical adenoma have co-expression of LH-R, cytochrome b5 and P450c17. These adenomas also express reductase and AMH. They do not express P450c21. Non-steroid producing adenomas did not show co-expression of cytochrome b5 and P450c17. All hyperplastic areas showed positive staining for the LH-receptor. None of them showed co-expression of cytochrome b5 and P450c17 or responded positively to hCG stimulation. Adrenocortical adenoma were found in the adrenal glands of ferrets which were surgically castrated, but also in the adrenal glands of ferrets which were treated with a GnRH-agonist. We concluded that a depot GnRH agonist is not able to prevent the formation of adenomas in the adrenal cortex of ferrets. These adenomas, however, were not steroid-producing. Further research is necessary to examine if these adenomas can become steroid-producing.