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Role of Luteal Glucocorticoid Metabolism during Maternal Recognition of Pregnancy in Women

Obstetrics and Gynaecology, Department of Reproductive and Developmental Sciences, University of Edinburgh (M.M., M.C.L., S.v.d.D., S.G.H., W.C.D.), and Royal Infirmary of Edinburgh (N.M., K.J.T.), Centre for Reproductive Biology, Queen’s Institute of Medical Research, Edinburgh EH16 4TJ, United Kingdom

Address all correspondence and requests for reprints to: Michelle Myers, Obstetrics and Gynaecology, The Queen’s Medical Research Institute Centre for Reproductive Biology, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom. E-mail: m.myers{at}sms.ed.ac.uk.

The human corpus luteum (hCL) is an active, transient, and dynamic endocrine gland. It will experience extensive tissue and vascular remodeling followed by 1) demise of the whole gland without any apparent scarring or 2) maintenance of structural and functional integrity dependent on conceptus-derived human chorionic gonadotropin (hCG). Because cortisol has well-characterized roles in tissue remodeling and repair, we hypothesized that it may have a role in controlling luteal dissolution during luteolysis and would be locally produced toward the end of the luteal cycle. Glucocorticoid-metabolizing enzymes [11ß-hydroxysteroid dehydrogenase (11ßHSD) types 1 and 2] and the glucocorticoid receptor (GR) were assessed in hCL and cultures of luteinized granulosa cells (LGC) using immunofluorescence and quantitative RT-PCR. Furthermore, the effect of cortisol on steroidogenic cell survival and fibroblast-like cell activity was explored in vitro. The hCL expressed 11ßHSD isoenzymes in LGC and nuclear GR in several cell types. hCG up-regulated the expression and activity of 11ßHSD type 1 (P < 0.05) and down-regulated type 2 enzyme (P < 0.05) in vitro and tended to do the same in vivo. Cortisol increased the survival of LGC treated with RU486 (P < 0.05) and suppressed the activity of a proteolytic enzyme associated with luteolysis in fibroblast-like cells (P < 0.05). Our results suggest that, rather than during luteolysis, it is luteal rescue with hCG that is associated with increased local cortisol generation by 11ßHSD type 1. Locally generated cortisol may therefore act on the hCL through GR to have a luteotropic role in the regulation of luteal tissue remodeling during maternal recognition of pregnancy.

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