Higher docosahexaenoic acid (DHA) in females compared with males suggests ovarian hormones increase DHA production. Eight-week old rats were ovariectomized or sham operated (SHAM), and ovariectomized rats were treated with implanted pellets providing 17 beta-estradiol (OVX+E), progesterone (OVX+P), both (OVX+PE) or neither (OVX) for 14 days. Immunoblot and fatty acid analysis were performed on all samples, and microarray analysis was performed on OVX and SHAM groups. Increased Delta 6-desaturase in OVX relative to SHAM was observed by microarray (12% higher) and immunoblot (31% higher). OVX+E and OVX+PE rats had 39% and 42% higher Delta 6-desaturase content, respectively, compared with OVX. OVX+E and OVX+PE also increased phospholipid DHA concentrations in liver (increase of 34% and 40%, respectively) and plasma (increase of 70% and 74%, respectively) relative to OVX. Progesterone exerted no effect on Delta 6-desaturase or DHA. These results indicate that 17 beta-estradiol increases DHA through increased Delta 6-desaturase, possibly explaining sex differences in DHA. (C) 2013 Elsevier Ltd. All rights reserved.