Role of local environmental factors in determining tissue-specific effects of estrogen: examination of uterine tissues transplanted to brain.
Estrogen stimulates uterine epithelial cells to divide, but not estrogen-concentrating neurons in the adult brain. This effect correlates with recent evidence that estrogen can induce the expression of certain growth-related genes in uterus which are not directly induced by estrogen in the adult brain. The possibility that local diffusible factors play a major role in determining tissue-specific effects of estrogen was examined by transplanting uterine tissues into the brain, muscle and kidney of adult rats and then comparing the effects of estrogen on the incorporation of [3H]thymidine and the expression of Fos-, cdc2- and Rb-like immunoreactivity (IR) on native and transplanted uterine tissues, as well as in estrogen-concentrating regions of the brain adjacent to the uterine grafts. In native uteri, estrogen treatment stimulated Fos-, cdc2-, and Rb-like IR, as well as [3H]thymidine incorporation, within lumenal and glandular epithelial cells. All of these effects were estrogen responsive--no immunoreactive staining within uterine epithelial cells and no signs of epithelial cell proliferation were observed in the native uteri of non-estrogen-treated animals. When uterine tissues were transplanted to brain, Fos-, cdc2-, and Rb-like IR epithelial cells, as well as many [3H]thymidine-incorporating uterine epithelial cells, were observed in all estrogen-treated animals and in some non-estrogen-treated animals as well. Identical results were obtained when uterine tissues were transplanted to skeletal muscle, but not to kidney (in the kidney, transplanted epithelial cells expressed all four parameters but only in estrogen-treated animals, comparable to the native uterus). In contrast, estrogen did not stimulate cell division and did not induce Fos-, cdc2-, or Rb-like IR within estrogen-concentrating neuronal regions of the ventromedial hypothalamus. In addition, the presence of uterine tissue in the brain did not confer the ability of estrogen to stimulate any of these parameters within nearby, estrogen-concentrating regions. These data suggest that there are factors in brain and muscle which can allow uterine epithelial cells to divide in the absence of estrogen. There was no evidence of a diffusible factor in brain which inhibits uterine epithelial cell division, nor of a diffusible factor in uterus which can confer estrogenic stimulation of growth-related genes and cell division to central nervous system neurons. In addition, the data provide the first evidence for estrogen regulation of cdc2 and Rb expression in normal uterus.
Okano
H J
HJ
Laboratory of Neurobiology and Behavior, Rockefeller University, New York, NY 10021.
Pfaff
D W
DW
Gibbs
R B
RB
D000818:Animals; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics; D002552:Cerebral Ventricles; D004261:DNA Replication / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016161:Genes, Retinoblastoma / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D007668:Kidney; D009132:Muscles; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D016042:Transplantation, Heterotopic; D014599:Uterus / Q000378:metabolism / Q000637:transplantation*
D004958:Estradiol; D016203:CDC2 Protein Kinase