Female reproductive status and circulating blood leukocyte expression of selected metabolic or signaling genes involved in sex steroid metabolism.

OBJECTIVE To examine the blood leukocyte expression of 22 sex steroid metabolic/signaling genes according to female reproductive status. METHODS Michigan Fisheaters' Cohort participants underwent blood collection during the luteal phase of the menstrual cycle or randomly in non-menstruating participants. Gene expression (GE) was measured using Taqman hydrolysis probes and quantitative RT-PCR. Repeatability of four genes was determined in a subgroup. RESULTS Five premenstrual, 57 premenopausal (20 users of systemic hormonal contraception), and 43 postmenopausal females participated. After Bonferroni correction for multiple comparisons of median GE between groups, three findings remained significant: greater GE of AhR in postmenopausal women than in premenopausal non-users of systemic hormonal contraception; and greater GE of ESR2 and HSD17B7 in premenstrual girls compared to postmenopausal women. Modest intra-class correlations were identified for CYP 19, ESR1, and ESR2 GE measured both in 2007 and 2010, but no intra-class correlation over the same time period was found for CYP17. CONCLUSIONS There was little differential variation of blood leukocyte sex steroid ge between premenopausal women in the luteal phase of the menstrual cycle and postmenopausal women for most genes analyzed, but it will be necessary to make statistical adjustments in future epidemiologic studies in two circumstances: 1) when comparing AhR GE in premenopausal women non-users of systemic hormone contraception with postmenopausal women and 2) when comparing ESR2 and HSD17B7 GE in studies that include premenstrual girls. Developmental differences may explain the differential GE found in ESR2 and HSD17B7 in premenstrual girls compared with postmenopausal women.