Growth Hormone 2024-1 PDF

Growth Hormone Author: Dr. Mariana Flores MD, MSC Modified by: Dr. Yisel Mi Guzmán Leguel Objectives Describe the regulation and mechanism of secretion of growth hormone (GH). Analyze the metabolic effects in the presence of GH. Discuss the actions of GH and insulin like growth factor I (IGF-I) in t...

Growth Hormone Author: Dr. Mariana Flores MD, MSC Modified by: Dr. Yisel Mi Guzmán Leguel Objectives Describe the regulation and mechanism of secretion of growth hormone (GH). Analyze the metabolic effects in the presence of GH. Discuss the actions of GH and insulin like growth factor I (IGF-I) in the regulation of growth, and the role of growth hormone in the fasted state. Integrate the physiological actions of GH and IGF-I with the pathophysiological aspects of deficiency or excess. Growth hormone Also called Somatotropic hormone or Somatotropin GH1 gene – Chromosome 17 Major anabolic growth-promoting hormone and stress hormone Childhood and adolescence: essential for the normal rate of body growth Secretory burst at puberty is induced by estrogens and testosterone Secreted throughout life; remains physiologically important. Decline in senescence IGF-1 synthesis is GH dependent Responsible with GH of pubertal growth IGF also called somatomedins SECRETION OF GH REGULATION OF GH Regulated by 2 opposing hypothalamic releasing hormones: GHRH stimulates GH secretion Somatostatin inhibits GH secretion by inhibiting the action of GHRH The net effect of these counteracting hormones on somatotrophs cells determines the rate of GH secretion REGULATION OF GH GH stimulates the production of insulin-like growth factor I & 2 (IGF-I & II) also known as somatomedins Mediates the growth-promoting action of GH. IGF-I is more dependent on GH than IGF2 ~60% GH circulate free in plasma ~40% GH-binding protein, increasing half-life somatomedins Starvation, fasting Hypoglycemia or low free fatty acids Exercise Trauma Deep sleep (stages III & IV) Elevation of amino acids Estrogens Hyperglycemia Obesity Increased glucocorticoids Late pregnancy High insulin levels OTHER FACTORS REGULATING GH PULSATILE SECRETION PATTERN GH Pulsatile secretion Requires normal thyroid hormone secretion. In maximal stimulation, the frequency of pulses increases, not the amplitude. During night non-REM sleep: stages III and IV. Effects of GH Minutes to hours Lipolysis in adipose cells Inhibition of glucose uptake by muscle Stimulation of gluconeogenesis by hepatocytes All these actions are anti-insulin or diabetogenic actions. Long term Promote tissue growth by stimulating target tissues to produce IGFs Metabolic effects PROTEINS Increase Protein synthesis Increased transport of Aa into the cell → increases the concentration of Aa → increases DNA, RNA, and protein synthesis Decrease CATABOLISM Proteins and amino acids GH enhances almost all facets of Aa: uptake and protein synthesis by cells, and reduces breakdown or proteins Metabolic effects Fat Release of fatty acids (Fa) from adipose tissue ↑ conversion of fatty acids to acetyl CoA and its subsequent utilization for energy. Ketogenic effect, excessive fat mobilization from adipose tissue in the liver form acetoacetic acid released into body fluids causing KETOACIDOSIS Under influence of GH fat is used for energy in preference to using CHO or proteins. Metabolic effects CARBOHYDRATES Decrease glucose uptake in tissues (adipose and skeletal muscle) Increase glucose production by liver Resulting in increased plasma glucose Increase insulin secretion Due to the increased blood glucose concentration Metabolic effects GH and INSULIN GH inhibits glucose use by muscle and adipose tissue and increases glucose production by the liver (opposite to insulin action) Insulin resistance in muscle and fat cells GH normally has a tonic inhibitory effect on the actions of insulin (like glucocorticoid hormones) Metabolic effects GH and INSULIN Patients with high GH levels (acromegaly or prolonged exogenous administration) may develop: Insulin resistance Elevated plasma insulin level Hyperglycemia (like diabetes mellitus type 2) Metabolic effects BONE AND CARTILAGE Increases linear growth Increase deposition of protein by chondrocytes and osteogenic cells Increases the widening of epiphyseal plates and bone growth at the ends of long bones Osteoblast deposits on surfaces of older bones Osteoclasts remove old bone Effects of GH Effects of IGF-1 Pathophysiology of GH Growth Hormone [GH] Excess The two major diseases Gigantism Acromegaly Growth Hormone [GH] Deficiency Pituitary dwarfism GH hypersecretion Gigantism Excessive GH before puberty and failure of the epiphyseal plates to close. GH hypersecretion ACROMEGALY Excessive GH secretion after puberty Cartilage and membranous growth continues Most common cause of acromegaly is a GH-secreting acidophilic adenoma Plasma glucose increases, but frank diabetes mellitus is not common in acromegaly GH hypersecretion GH hyposecretion Pituitary dwarfism GH deficiency in childhood Decrease in the rate of body growth. If left untreated, results in pituitary dwarfism. This condition may result from: Deficiency in GH only Or multiple anterior pituitary hormone deficiencies A defect in the mechanisms that control GH secretion or the production of GH Failure in the target cells response for GH as consequence of different mutations in the GH receptor. Clinical case A 27-year-old woman had persistent headaches and amenorrhea. In addition, the size of her foot was increased by 0.5 cm for 6 months and lower jaw protrusion was observed. Swelling of superciliary arch, hypertrophy of nose and lip, macroglossia, lower jaw protrusion, enlargement of feet & hands, thyroid gland enlargement, and bitemporal hemianopsia. There were no abnormalities in heart and lung sounds and abdomen. https://www.frontiersin.org/articles/10.3389/fendo.2021.659076/full Clinical case Labs: GH, 51.12 ng/ml IGF-1, 1,538.9 ng/ml Glucose suppression test: after 75 g of glucose, GH was 8 µg/L ( N < 1) Free triiodothyronine (FT3), 5.56 pg/ml Free thyroxine (FT4), 2.52 ng/dl TSH, 2.26 μU/ml. Thyroid-related antibodies including anti-Tg antibody, anti-TPO antibody and thyroid receptor antibody were all negative. References Boron, W., Boulpaep, E. (2009). Medical Physiology. (2nd Ed.). Philadelphia: Mosby-Elsevier. Guyton, A., Hall, J. (2016). Textbook of Medical Physiology. (13th Ed.). Philadelphia: Elsevier-Saunders. Koeppen, S., Stanton, S. (2008). Berne & Levy Physiology. (6th Ed.). Philadelphia: Mosby-Elsevier Case Report: A Case of Pituitary Adenoma Producing Growth Hormone and Thyroid-Stimulating Hormone Simultaneously, Front. Endocrinol., 22 March 2021 | https://doi.org/10.3389/fendo.2021.659076