Description of Research Goals and Interests
Sarah Lundin-Schiller

Oxytocin and oxytocin induced prostaglandin biosynthesis are important in the mechanisms of luteal regression and parturition in sheep, cows, and pigs. Porcine endometrial and myometrial cell cultures are promising systems for the study of the regulation of oxytocin receptor expression, prostaglandin biosynthesis and the interactions between oxytocin receptor activation, prostaglandins, and other endocrine factors. Studies from our lab and others have shown that oxytocin receptor expression can be measured in the membrane fractions prepared from these cell cultures. It is has been shown that while estradiol upregulates oxytocin receptors, progesterone and interferon-tau downregulates oxytocin receptors. The molecular mechanism of up and down regulation by these factors still warrant further investigation. In addition the interplay among these factors has yet to be completely defined. My research goals are:

1) To continue to define the ultrastructural and biochemical characteristics of endometrial and myometrial primary cultures prepared from porcine uteri. Example questions include:
What is the nature of the cytoskeletal elements in the cell cultures?
What type of prostaglandins are produced by the endometrial cell cultures?
What is the affinity constant of oxytocin receptors on the cell cultures?
How does the prostaglandin biosynthesis change in response to oxytocin? or to other factors?

2) To identify factors that effect oxytocin receptor expression. We and others have shown that estradiol up regulates the oxytocin receptor in these tissues.

How is this response to estradiol affected by pretreatment with progesterone or progesterone cotreatment?
What other factors might be identified that affect oxytocin receptor expression? Does interferon and progesterone down regulate porcine receptors? Do high concentrations of oxytocin itself down regulate the oxytocin receptor?

3) To elucidate the mechanism of up and down regulation of the oxytocin receptors in these cells.

Does down regulation involve removal of receptors from the surface and degradation or recycling?
If down regulation involves endocytosis of surface receptors, how are actin filaments and actin associated proteins involved?
Does down regulation involve competitive binding as has been suggested for progesterone?
Does up regulation involve increased transcription rates, increased mRNA life span, increased translation, and/or increased exocytosis of previously synthesized receptor protein?

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