Hypocortisolism in the South African Angora goat: The role of 3βHSD

Abstract

South African Angora goats are susceptible to cold stress, due to their inability to produce sufficient levels of cortisol. During adrenal steroidogenesis the production of cortisol relies on the activity of two key enzymes, namely cytochrome P450 17alpha-hydroxylase and 3beta-hydroxysteroid dehydrogenase. Cytochrome P450 17alpha-hydroxylase has previously been identified as a factor contributing to hypocortisolism in the South African Angora goat. In this comparative study, the catalytic activity of Angora and ovine 3beta-hydroxysteroid dehydrogenase, which differ by five amino acid residues, was characterized. The conversion of 17-hydroxypregnenolone and dehydroepiandosterone to their corresponding products, 17-hydroxyprogesterone and androstenedione, by the two enzymes differed significantly. The enzymes were subsequently co-expressed with Angora P450 17alpha-hydroxylase. Major differences were observed in pregnenolone metabolism with a significant reduction in the formation of the cortisol precursor, 17-hydroxyprogesterone, by cells expressing Angora 3beta-hydroxysteroid dehydrogenase, implicating 3beta-hydroxysteroid dehydrogenase as an additional factor contributing to hypocortisolism in the South African Angora goat.