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- Bondestam, Jonas, et al.
(författare)
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Engagement of activin and bone morphogenetic protein signaling pathway Smad proteins in the induction of inhibin B production in ovarian granulosa cells
- 2002
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Ingår i: Molecular and Cellular Endocrinology. - 0303-7207 .- 1872-8057. ; 195:1-2, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- In the mammalian ovary cell growth and differentiation is regulated by several members of the transforming growth factor beta (TGF beta) superfamily including activins, inhibins, growth differentiation factors and bone morphogenetic proteins (BMPs). The effects of TGF beta family members are mediated to the target cells via heteromeric complexes of type I and II serine/threonine kinase receptors which activate Smad signaling protein pathways in various cell types. We have previously shown that inhibin B, a hormonally important product from human granulosa cells, is up regulated by activin and BMPs. Here, we report the use of adenoviral gene transfer methodology to manipulate the TGF beta growth factor signaling system in primary cultures of human granulosa cells. These cells are exceedingly difficult to transfect by conventional transfection methods, but were virtually 100% infected with recombinant adenoviruses expressing green fluorescent protein (GFP). Adenoviruses expressing constitutively active forms of the seven known mammalian type I activin receptor-like kinase receptors (Ad-caALK1 through Ad-caALK7) cause activation of endogenous and adenovirally transferred Smad signaling proteins so that Ad-caALK1/2/3/6 and Ad-caALK4/5/7 induced phosphorylation of the Smad1 and Smad2 pathways, respectively. Activin A and BMP-2 activated the Smad1 and Smad2 pathways as well as inhibin B production as did all the Ad-caALKs. Furthermore, overexpression of adenoviral Smad1 and Smad2 proteins without exogenously added ligands induced inhibin B production. The inhibitory Smad7 protein suppressed BMP-2 and activin induced inhibin B production. Collectively, the present data demonstrate that adenoviral gene transfer provides an effective approach for dissecting the TGF beta signaling pathways in primary ovarian cells in vitro and more specifically indicate that the Smad1 and Smad2 pathways are involved in the regulation of inhibin B production by TGF beta family ligands in the ovary.
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| 7. |
- Liu, Kui, et al.
(författare)
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Expression pattern and functional studies of matrix degrading proteases and their inhibitors in the mouse corpus luteum
- 2003
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Ingår i: Molecular and Cellular Endocrinology. - 0303-7207 .- 1872-8057. ; 205:1-2, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- The formation of the corpus luteum (CL) is accompanied with angiogenesis and tissue remodeling and its regression involves tissue degradation. Matrix degrading proteases such as plasminogen activators (PAs) and matrix metalloproteinases (MMPs) are thought to play important roles in such controlled proteolytic processes. In this study, in situ hybridization has been used to examine the regulation and expression pattern of mRNAs coding for proteases and protease inhibitors belonging to the PA- and MMP-systems during the life cycle of the CL in an adult pseudopregnant mouse model. Of the nine proteases and five protease inhibitors that were studied, the majority were found to be temporally expressed during the formation and/or the regression of the CL. However, the mRNAs coding for urokinase type PA (uPA), membrane-type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type-3 (TIMP-3) were constantly expressed in the mouse CL throughout its whole life span. To study the functional role of uPA in the CL, we analyzed luteal formation and function in uPA deficient mice. Our results revealed no significant difference in ovarian weight, serum progesterone levels, and blood vessel density in the functional CL between uPA deficient and wild type control mice. The temporal and spatial expression pattern of proteases and protease inhibitors during the CL life span suggests that members of the PA- and MMP-systems may play important roles in the angiogenesis and tissue remodeling processes during CL formation, as well as in the tissue degradation during luteal regression. However, the absence of reproductive phenotypes in mice lacking uPA and several other matrix degrading proteases indicates that there are redundancies among different matrix degrading proteases or that tissue remodeling in the ovary may involve other additional unique elements.
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