Relative contribution of P450c17 towards the acute cortisol response: Lessons from sheep and goats

•Cortisol production was altered in sheep and goats bred for commercial value.•Sheep and goats have unique P450c17 genotypes, encoding two distinct isoforms.•P450c17 genotypes alter physiological and behavioural responses to acute stress.•P450c17 action downstream of pregnenolone contributes to acute cortisol regulation.•These effects of P450c17 are dependent on an individual's genetic makeup.

The rapid release of cortisol from the adrenal cortex upon ACTH receptor activation plays an integral role in the stress response. It has been suggested that the quantitative control over adrenal steroidogenesis (quantity of total steroids produced) depends on the activities of cytochrome P450 side-chain cleavage and steroidogenic acute regulatory protein that supplies pregnenolone precursor to the pathway. The qualitative control (which steroids) then depends on the downstream steroidogenic enzymes, including cytochrome P450 17α-hydroxylase/17,20-lyase (P450c17). In this review we focus on the relative contribution of P450c17 in the qualitative control of cortisol production with data collected from studies on South African Angora and Boer goats, as well as Merino sheep. Unique P450c17 genotypes were identified in these breeds with isoforms differing only with a couple of single amino acid residue substitutions. This review demonstrates how molecular and cellular differences relating to P450c17 activity can affect physiological and behavioural responses.