Function and Regulation of Growth Hormone Signaling During Food Deprivation
Date of Award
Spring 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Immunobiology
First Advisor
Medzhitov, Ruslan
Abstract
Favorable environmental conditions promote organism’s growth and reproduction, while unfavorable conditions result in resource allocation toward defense against environmental challenges. The choice between these programs is controlled by hypothalamic-pituitary axes. Growth hormone (GH) is largely implicated in the control of somatic growth either directly or via effectors such as insulin-like growth factor 1 (IGF1). However, the plasma level of GH is also elevated in adverse environments, such as food deprivation, cold exposure and infection. This dissertation addresses the apparent dichotomy surrounding elevation of serum GH levels during food deprivation, by examining the signaling, regulation, and function of the GH in the fed versus fasted state. Chapter 1 provides the necessary background for the topics discussed in this dissertation. Life history theory and its application to cellular and organismal physiology are briefly introduced. Furthermore, the GH-IGF1 axis and its known effects on organismal metabolism are discussed. In Chapter 2 the effect of food deprivation on the GH-IGF1 axis and GHR signaling is examined. Utilizing in vitro approaches, novel mechanisms modulating the outcome of GHR signaling during food deprivation are identified. Chapter 3 explores the unique transcriptional program induced by the GH in the fed versus fasted state. In Chapters 4 and 5, genetic approaches are used to determine the state-dependent function of GHR signaling in the liver and adipose tissue. Lastly, Chapter 6 expands on the implications of some of the findings in this dissertation.
Recommended Citation
Yaghoubi, Parastou, "Function and Regulation of Growth Hormone Signaling During Food Deprivation" (2023). Yale Graduate School of Arts and Sciences Dissertations. 998.
https://elischolar.library.yale.edu/gsas_dissertations/998
