We have previously investigated the ability of glucocorticoids secreted by the adrenal cortex to directly influence gonadal function. In contrast, the primary aim of the present study was to assess whether increased progesterone output from the corpus luteum on day 14 of the ovine oestrous cycle can alter adrenal metabolism (and hence output) of cortisol relative to oestrous cycle day 5. Since cortisol-cortisone inter-conversion by the cloned 11β-hydroxysteroid dehydrogenase (11βHSD) enzymes is subject to regulation by peroxisome proliferator-activated receptors, known to be activated by polyunsaturated fatty acids (PUFA), a supplementary objective was to assess potential effects of a PUFA-enriched diet on adrenal cortisol oxidation. Having been maintained on a control diet or one enriched for linoleic acid (18:2, n6) for 6 weeks, Welsh mountain ewes were sacrificed on days 5 (n=5) and 14 (n=13) of the oestrous cycle. Adrenal glands were homogenized in phosphate-buffered saline and 11βHSD activities were subsequently quantified over 1 hour using a radiometric conversion assay with 100 nM [3H]-cortisol plus 4 mM NADP+ or NAD+. Since there were no significant differences in either NADP+- or NAD+-dependent oxidation of cortisol between adrenal glands from sheep fed the n-6 PUFA-enriched versus control diets, data were pooled irrespective of diet for each day of the cycle. NAD+-dependent cortisol oxidation exceeded the level of NADP+-dependent cortisol metabolism by 11- to 23-fold, and while there was no significant difference in NADP+-dependent cortisol metabolism between days 5 and 14 of the cycle, NAD+-dependent cortisol was decreased by 62±8% on day 14 versus day 5 of the cycle (P<0.001). In an in vitro assay, progesterone completely inhibited NAD+-dependent cortisol metabolism by ovine adrenal tissue homogenates with an IC50 of 156 nM. Hence, it would appear that increased ovarian secretion of progesterone in the late luteal phase can suppress adrenal metabolism of cortisol by 11βHSD2.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.