THU049 Growth Hormone Treatment Reverses Deficits In POU1F1 Gene Mutation

Disclosure: S. Al-Samerria: None. J. Phelan: None. H. Xu: None. A. Negron: None. F. Wondisford: None. S. Radovick: None. Mutations in the Pit 1 gene, also known as POU1F1, have been linked to the deficient development of somatotrophs and the synthesis of growth hormone (GH) in the anterior pituitary gland. In a previous study, we reported a point mutation in the PIT1 gene caused by a substitution of a lysine (K) with a glutamic acid (E) at position 216 (K216E) on one allele in a patient presenting with combined pituitary hormone deficiency (CPHD). This patient had undetectable levels of GH, TSH, very low PRL, and severe mental retardation associated with short stature (SS). To study the effects of GH treatment on growth and metabolism in CPHD, we created a unique mouse model with the K216E mutation in the PIT1 gene using the CRISPR/Cas9 genome editing system. In this study, 4-week-old male and female homozygous mice were randomly divided into two groups. The treatment group received subcutaneous injections of GH (5 mg/g/day) for 5 consecutive days per week for 4 weeks, while the control group received saline injections on the same schedule. GH treatment significantly improved the growth and body composition of male and female mice bearing the K216E. GH treatment also increased metabolism as measured by oxygen consumption, carbon dioxide production, and energy expenditure. These effects were observed both during treatment and 4 weeks post-treatment, although some reversal of the changes in body composition was observed 4 weeks post-treatment. Our findings demonstrate the utility of this mouse model in studying the effects of GH deficiency and treatment on growth and metabolism. This model holds great promise in advancing our understanding of the underlying mechanisms of hypopituitarism and CPHD, potentially serving as a valuable tool in identifying metabolic biomarkers for these conditions. Presentation: Thursday, June 15, 2023