Glycoconjugates are ubiquitous components of cell surfaces and are generally believed to play key roles in cell recognition events. Implantation is a dynamic example of cell-cell recognition and adhesion. The timing of implantation must be coordinated carefully since both the embryo and the uterus must develop simultaneously to a state competent for implantation. This receptive uterine state is transient and is under the strict control of the steroid hormones, estrogen and progesterone. It appears that these steroid hormones act primarily on the uterine tissue and not the embryo, since in the presence of serum embryos can attach to and """"""""implant"""""""" on plastic substrata or cell layers in vitro regardless of what steroid hormones are present in the culture medium. Steroid hormones dramatically influence the ability of uteri to synthesize glycoconjugates; moreover, studies of changes occurring on uterine cell surfaces indicate that glycoconjugates are likely to mediate aspects of implantation. Collectively, these observations provide strong correlations between the ability of steroid hormones to regulate uterine receptivity and glycoconjugate assembly. It is important to determine the molecular basis by which steroids modulate uterine glycoconjugate synthesis, if we are to understand how these molecules function in uterine cell recognition events. Improper regulation of these processes could lead to spontaneous abortion or uterine abnormalities. This proposal is aimed at determining how steroid hormones regulate the synthesis of N-linked glycoproteins and hyaluronic acid (HA), in uteri. Studies performed in the Principal Investigator's laboratory indicate that one class of N-linked oligosaccharides, lactosaminoglycans (LAGs), as well as HA, a component of extracellular matrices, can support implantation-related, cell adhesion events. Furthermore, the synthesis of both LAGs and HA are modulated dramatically by steroid hormones and during early pregnancy. A series of sensitive biochemical techniques will be applied to determine how steroid hormones affect the levels of sugar nucleotide and glycolipid precursors, glycosyltransferases and mRNA utilized the LAG and HA assembly by uteri. The data obtained will contribute to our general understanding of the regulation of glycoprotein synthesis as well as the biochemical processes that control implantation.
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| Carson, D D; Farrar, J D; Laidlaw, J et al. (1990) Selective activation of the N-glycosylation apparatus in uteri by estrogen. J Biol Chem 265:2947-55 |
| Dutt, A; Carson, D D (1990) Lactosaminoglycan assembly, cell surface expression, and release by mouse uterine epithelial cells. J Biol Chem 265:430-8 |
| Carson, D D; Tang, J P (1989) Estrogen induces N-linked glycoprotein expression by immature mouse uterine epithelial cells. Biochemistry 28:8116-23 |
| Carson, D D; Tang, J P; Julian, J et al. (1988) Vectorial secretion of proteoglycans by polarized rat uterine epithelial cells. J Cell Biol 107:2425-35 |
| Carson, D D; Tang, J P; Hu, G (1987) Estrogen influences dolichyl phosphate distribution among glycolipid pools in mouse uteri. Biochemistry 26:1598-606 |
