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Int J Mol Epidemiol Genet 2012;3(2):134-143

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

Janet R Osuch, Wei-Wen Hsu, David Todem, Jeffrey Landgraf, Dorota Mikucki, Pam S Haan, Wilfried Karmaus

Departments of Surgery and Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East
Lansing, MI, USA; Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East
Lansing, MI, USA; Research Technology Support Facility, Michigan State University, East Lansing, MI, USA; Department of
Epidemiology and Biostatistics, Arnold School of Public Health, University Of South Carolina, Columbia, SC, USA

Received March 30, 2012; accepted April 15, 2012; Epub May 15, 2012; Published May 30, 2012

Abstract: 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. (IJMEG1203003).

Keywords: Steroid gene expression, blood leukocyte gene expression, female reproductive status


Address all correspondence to:
Dr. Janet Osuch
Departments of Surgery and Epidemiology and Biostatistics
College of Human Medicine, Michigan State University
West Fee Hall, 909 Fee Road, Room 632
East Lansing, Michigan, USA.
Tel: 517-353-6823 extension 127; Fax: 517-432-1130
E-mail: janet.osuch@hc.msu.edu