title: A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus.
abstract: The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women.
authors.affiliation: Medical Research Council Centre for Inflammation Research, The Queen's Medical Research Institute, EH16 4TJ, Edinburgh, United Kingdom.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Simitsidellis
authors.affiliation: Medical Research Council Centre for Inflammation Research, The Queen's Medical Research Institute, EH16 4TJ, Edinburgh, United Kingdom.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Gibson
authors.affiliation: Medical Research Council Centre for Inflammation Research, The Queen's Medical Research Institute, EH16 4TJ, Edinburgh, United Kingdom.
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Cousins
authors.affiliation: Medical Research Council Centre for Inflammation Research, The Queen's Medical Research Institute, EH16 4TJ, Edinburgh, United Kingdom.
authors.forename: Arantza
authors.initials: A
authors.lastname: Esnal-Zufiaurre
authors.affiliation: Medical Research Council Centre for Inflammation Research, The Queen's Medical Research Institute, EH16 4TJ, Edinburgh, United Kingdom.
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D013196:Dihydrotestosterone