Type of Document Dissertation Author Toporikova, Natalia Author's Email Address firstname.lastname@example.org URN etd-03272007-233650 Title Regulation of Rhythmic Prolactin Secretion: Combined Mathematical and Experimental Study Degree Doctor of Philosophy Department Mathematics, Department of Advisory Committee
Advisor Name Title De Witt Sumners Committee Member Joel Tabak-Sznajder Committee Member John Quine Committee Member Marc E. Freeman Committee Member Richard Bertram Committee Member Keywords
- Phase Plane
- Slow Variable
Date of Defense 2007-03-21 Availability unrestricted AbstractThe focus of this work is pulsatile prolactin (PRL) secretion, which includes in vivo experiments on PRL release in female rats and mathematical modeling at the system and single-cell level .
First we investigate the generation of the semicircadian rhythm of PRL that occurs during the first half of pregnancy in female rats. Using an experimental approach we show that this rhythm can be induced by the injection of oxytocin, suggesting that this hormone is responsible for triggering the rhythm. Using mathematical modeling, we propose a likely mechanism for this effect. According to this model, the PRL rhythm is generated by the interaction of hypothalamic neurons and pituitary lactotrophs.
In the second part of this work we study PRL release on the single-cell level. First we develop a mathematical model of the pituitary lactotroph and use it to identify the mechanism for the stimulatory effects of dopamine (DA) on lactotrophs. These effects are paradoxical since DA activates only inhibitory ionic currents. We also show cases of bursting in the absence of a slow variable and analyze the dynamic mechanism for this novel form of bursting.
Finally, we develop a mathematical model of the effect of endothelin (ET) on PRL secretion from pituitary lactotrophs. This model combines four different biochemical signaling pathways, each of which is activated by ET and mediated by G-proteins.
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