New aspects of estrogen action in the endometrium: Reciprocal interplay with retinoic acid pathway and a novel estrogen-regulated gene

The uterine endometrium is a major target for the estrogen. However, the molecular basis of estrogen action in the endometrium is largely unknown. I have used two approaches to study the effects of estrogen on the endometrium. One approach involved the study of the interaction between estrogen and retinoic acid (RA) pathways in the endometrium. I have demonstrated that estrogen administration to rodents and estrogen replacement therapy (ERT) in postmenopausal women selectively induced the endometrial expression of retinaldehyde dehydrogenase II (RALDH2), a critical enzyme of RA biosynthesis. RALDH2 was expressed exclusively in the stromal cells, especially in the stroma adjacent to the luminal and glandular epithelia. The induction of RALDH2 by estrogen required estrogen receptor and occurred via a direct increase in RALDH2 transcription. Among the three RA receptors, estrogen selectively induced the expression of RARα. In parallel, estrogen also increased the utilization of all-trans retinol (the substrate for RA biosynthesis) and the expression of two RA-regulated marker genes, cellular retinoic acid binding protein II (CRABP2) and tissue transglutaminase (tTG) in the endometrium. Thus estrogen coordinately upregulated both the production and signaling of RA in both the rodent and human endometrium. This coordinate upregulation of RA system appeared to play a role in counterbalancing the stimulatory effects of estrogen on the endometrium, since the depletion of endogenous RA in mice led to an increase in estrogen-stimulated stromal proliferation and endometrial Akt phosphorylation. In addition, I have also used a systematic approach (DNA microarray) to categorize genes and pathways affected by the ERT in the endometrium of postmenopausal women and identified a novel estrogen-regulated gene EIG121. EIG121 was exclusively expressed in the glandular epithelial cells of the endometrium and induced by estrogen in vivo and in cultured cell lines. Compared with the normal endometrium, EIG121 was highly overexpressed in type 1 endometrial cancer, but profoundly suppressed in type 2 endometrial tumors. Taken together, these studies suggested that estrogen regulates the expression of many genes of both the pro-proliferative and anti-proliferative pathways and the abnormality of these pathways may increase the risks for estrogen-dependent endometrial hyperplasia and endometrial cancer. ^

Exploring professional orientations to community voice in professional practice settings: The IMAP process

The tension between technical experts and the populations they seek to serve is well established in the literature examining professional social problem solving. In this piece, I examine this tension as one between the distinct discursive worlds of technical expertise and community voice. I develop an analytic process, IMAP, for exploring this tension by looking at a wide variety of professional orientations around a relatively fixed concept of community voice. IMAP involves I&barbelow;dentifying social problem solvers, M&barbelow;apping social problem solvers' claims, A&barbelow;nalyzing professional orientations that arise from this mapping, and P&barbelow;redicting, diagnosing, and remediating conflicts. IMAP can be used by analysts external to social problem solving settings or by social problem solvers themselves. The use of IMAP by external experts poses questions of expert alignment with either of the discursive worlds. I examine two cases in public health practice settings: a mobile immunization service and the efforts of a foundation to improve health in an inner-city neighborhood. I develop four modal types that can be anticipated in social problem solving settings or, more specifically, in public health practice. Understanding of these “world views” can enhance mutual understanding between public health professionals and between public health professionals and the communities they seek to serve. IMAP might also address ongoing conflicts to clarify differences in unspoken normative commitments and the impact of these on social problem solving. I discuss implications of the research for public health practice and further research in the area. ^