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This Article Full Text Full Text (PDF) All Versions of this Article: 70/5/1349    most recent biolreprod.103.024786v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kowalski, A. A. Articles by Simmen, R. C.M. Search for Related Content PubMed PubMed Citation Articles by Kowalski, A. A. Articles by Simmen, R. C.M. Agricola Articles by Kowalski, A. A. Articles by Simmen, R. C.M.

Uterine Androgen Receptors: Roles in Estrogen-Mediated Gene Expressionand DNA Synthesis¹

Interdisciplinary Concentration in Animal Molecular and Cell Biology,³ University of Florida,Gainesville, Florida 32611-0910 Arkansas Children's Nutrition Center and the Department of Physiology and Biophysics,⁴ University of Arkansasfor Medical Sciences, Little Rock, Arkansas 72202

The localization of androgen receptors (AR) and their ligands in the uterine microenvironment at early pregnancy suggest a role for AR in uterine physiology. We have evaluated AR expression in the pig uterine endometrium and examined whether AR ligands modulate peri-implantation uterine gene expression. Northern blot analysis demonstrated the 10.5 kilobase AR transcript in endometrium. Endometrial levels of AR mRNA and protein were greater at early than at mid- or late pregnancy. Estrogen receptor- mRNA levels showed similar maximal expression at early pregnancy. Immunocytochemical analysis of endometrium at early pregnancy localized AR to nuclei of glandular epithelial (GE) and stromal (ST) cells. To evaluate a role for AR in uterine gene regulation, the levels of mRNAs for insulin-like growth factor-I (IGF-I), proliferative cell nuclear antigen (PCNA), and AR itself were assessed in uterine endometrial explant cultures treated with estradiol-17ß (E), testosterone (T), and 19-nortestosterone (N). Induction by E of AR mRNA abundance occurred in endometrium from Day 10 but not from Day 12 pregnant animals and this was partially blocked by coaddition of N or T, although neither androgen alone had any effect. Abundance of IGF-I and PCNA mRNAs was increased by E and inhibited by coaddition of either T or N in Day 10 pregnant pig endometrium. In endometrium from Day 12 pregnant animals, addition of either N or T with E increased IGF-I mRNA levels over that of controls, although E alone was without effect. In contrast, PCNA mRNA abundance was suppressed by all steroid treatments in these explants. DNA synthesis in primary cultures of GE cells from endometrium at Days 10 and 12 of pregnancy was increased by E and was suppressed by T, the latter only at Day 12. E did not affect DNA synthesis in ST cells from endometrium at either pregnancy day, although T inhibited this process in an E-dependent manner in ST cells from pregnancy Day 12. Results identify AR in the pig endometrium during the window of maternal receptivity for implantation and demonstrate the functional, albeit complex, interactions of androgens and estrogens in the regulation of uterine endometrial gene expression and cell growth in vitro. Further elucidation of the role of androgens and their receptor in early pregnancy events may be relevant to an understanding of peri-implantation embryo loss.

¹ Supported, in part, by grants from the National Institutes of Health (HD21961) and USDA (98-35205-6739) and by USDA-CRIS6251-5100- 002-06S to the Arkansas Children's Nutrition Center.

² Correspondence: Rosalia C.M. Simmen, Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, and Arkansas Children's Nutrition Center, 1120 Marshall Street, Little Rock, Arkansas 72202. FAX: 501 364 3161; simmenrosalia{at}uams.edu

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