Smad 3 regulates proliferation of the mouse ovarian surface epithelium.
Smad 3 is a signaling intermediate for the transforming growth factor beta (TGFbeta) family; however, little is known about the role this protein plays in the regulation of the ovarian surface epithelium (OSE). Using a transgenic mouse model, we found that in the absence of Smad 3 there was a distinct morphological alteration of OSE cells. Wild-type (WT) OSE was flat with thin cells, while Smad 3-deficient (Smad 3 -/-) OSE was thick with plump cuboidal cells. WT OSE had less immunostaining for proliferating cell nuclear antigen (PCNA) and estrogen receptor alpha (ERalpha) than Smad 3 -/- OSE. However, there were no differences in the number of apoptotic cells or Bax and Bcl-2 levels between WT and Smad 3 -/- OSE. Although WT mice had higher levels of serum estradiol than Smad 3 -/- mice, WT and Smad 3 -/- mice had similar levels of progesterone. These data suggest that Smad 3 regulates OSE morphological appearance and proliferation in the absence of high serum estradiol levels or alterations in progesterone levels.
Symonds
Daniel
D
Department of Epidemiology and Preventive Medicine, Program in Toxicology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. jflaws@epi.umaryland.edu
Tomic
Dragana
D
Borgeest
Christina
C
McGee
Elizabeth
E
Flaws
Jodi A
JA
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D051900:Smad3 Protein; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; D051028:bcl-2-Associated X Protein; D011374:Progesterone; D004958:Estradiol