The suppressor of cytokine signaling ( SOCS ) proteins have been identified as important regulators of cytokine signaling. SOCS - 3 has been identified as being essential for normal fetal growth and survival, with the null mutation of the socs - 3 gene resulting in embryo death. The specific role of SOCS - 3 in fetal development, however, has yet to be characterized. Therefore, the overall aim of this thesis was to identify and quantify SOCS - 3 mRNA in a range of fetal tissues in the sheep. After identification of SOCS - 3 expression in fetal tissues, we then aimed to determine the ontogenic profile of SOCS - 3 in three key fetal tissues ; the liver, adipose tissue and adrenal gland, and whether SOCS - 3 expression in these tissues was altered after withdrawal and stimulation of prolactin ( PRL ). SOCS - 3 mRNA was found to be differentially expressed in a range of fetal tissues in late gestation and was higher in the fetal liver than in the pancreas, spleen and kidney. SOCS - 3 expression increased throughout gestation in the fetal liver, however, its expression decreased in the fetal adipose tissue and adrenal in late gestation. The pituitary hormone PRL has previously been implicated as a fetal growth factor. In the sheep fetus, PRL receptors are expressed in the fetal liver, adipose tissue and adrenal. We aimed to determine whether PRL plays a role in the maintenance of SOCS - 3 expression in the liver, adipose tissue and adrenal gland in late gestation, and whether SOCS - 3 expression can be regulated by acute PRL stimulation. We have demonstrated that PRL withdrawal suppressed SOCS - 3 expression in the liver, whereas acute PRL stimulation upregulated SOCS - 3 expression in the adrenal. Neither PRL withdrawal nor stimulation had an effect on SOCS - 3 expression in the adipose tissue. In summary, the data presented in this thesis would suggest that SOCS - 3 has tissue specific functions in late gestation. Furthermore, its expression is regulated in a tissue specific manner in response to the withdrawal or acute stimulation by PRL This provides the first evidence to suggest that the fetal liver and adrenal are both sensitive to either chronic or acute changes in plasma PRL concentrations, measured as the suppression or upregulation of SOCS - 3. We speculate that changes in SOCS - 3 mRNA expression relates to the regulation of growth and functional maturation of fetal tissues throughout gestation, and that PRL may represent an important factor which acts to alter SOCS - 3 expression in key fetal tissues. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2006.
| Identifer | oai:union.ndltd.org:ADTP/263712 |
| Date | January 2006 |
| Creators | Gentili, Sheridan |
| Source Sets | Australiasian Digital Theses Program |
| Language | en_US |
| Detected Language | English |
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