Bachelor of Science (BS), Ohio University, 2023, Biological Sciences
Growth hormone deficiency is a condition that results from insufficient production and secretion of growth hormone (GH) from the pituitary gland. Since GH has numerous physiological activities and acts on most tissues of the body, recombinant GH has been approved for treatment of GH deficiency in children and adults (Hintz, 2004). However, while GH is crucial for proper growth and development and maintenance of body composition, it also has covert actions that can be detrimental to health. These covert actions include 1) GH has diabetogenic activity (inhibits insulin action) (Ader et al., 1987; Bornstein et al., 1969; Cameron & Kostyo, 1987; Houssay, 1936; Lostroh, 1974; Luft & Cerasi, 1968; Rabinowitz et al., 1965; Rabinowitz & Zierler, 1963; Takahashi et al., 2001) 2) GH downregulates xenobiotic metabolizing enzymes which impairs stress resistance (Amador-Noguez et al., 2004, 2007; Jiang et al., 2013; Steinbaugh et al., 2012) 3) GH can increases fibrosis (Kopchick et al., 2022) and 4) GH can promote the growth of certain cancers. Since GH binds with high affinity to the GH receptor (GHR) and the prolactin receptor (PRLR), GH's proliferative effect on cancer is thought to be mediated though GHR as well as PRLR signaling (Cunningham et al., 1990; Jacobson et al., 2010; Neradugomma et al., 2014; Thomas et al., 2015; Wen et al., 2014). As such, the lactogenic action of GH (GH signaling through the PRLR) has positive and negative health effects as it helps promote lactation but also promotes the growth of PRLR positive cancers.
The presence of these covert actions may partially explain why GH is described as a pro-aging hormone (i.e., elevated GH levels are associated with decreased lifespan while reduced GH action is associated with increased lifespan in numerous species (Berryman et al., 2008; Junnila et al., 2013)). Because of this, our laboratory is studying a variant of GH (GHv) that has diminished diabetogenic and lactogenic activities in efforts to determine (open full item for complete abstract)
Committee: Edward List (Advisor)
Subjects: Aging; Biology; Cellular Biology; Endocrinology; Molecular Biology