Extracellular matrix integrity: a possible mechanism for differential clinical effects among selective estrogen receptor modulators and estrogens?
Recent gene microarray studies have illustrated heterogeneity in gene expression changes not only between estrogens and selective estrogen receptor modulators (SERMs), but also across different SERM molecules. In ovariectomized rats, this phenomenon was observed with respect to a number of genes involved in collagen turnover and extracellular matrix (ECM) integrity in the uterus and vaginal tissues. Preliminary mechanistic data suggest that these effects on ECM integrity may have relevance in the context of the effect of estrogens and some SERMs to increase the risk of pelvic organ prolapse and the incidence of urinary incontinence in postmenopausal women. Given the pivotal role of ECM integrity and collagen turnover in other tissues and disease states, these processes may provide a fruitful target for future research into the mechanisms for the heterogeneous pharmacology of estrogens and SERMs across different cell types and target tissues.
Cox
David A
DA
Muskuloskeletal Research Division, Lilly Research Laboratories, Indianapolis, IN 46285, USA.
Helvering
Leah M
LM
D000818:Animals; D003560:Cysts / Q000139:chemically induced; D016889:Endometrial Neoplasms / Q000139:chemically induced; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia; D008666:Metalloendopeptidases / Q000378:metabolism; D011127:Polyps / Q000139:chemically induced; D017698:Postmenopause; D051381:Rats; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000494:pharmacology*; D014549:Urinary Incontinence / Q000139:chemically induced; D014596:Uterine Prolapse / Q000139:chemically induced; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D008666:Metalloendopeptidases