Growth Hormone (GH) PDF

Lecture 3 Dep. of Medical Physiology Dr.HananAltaee Growth hormone (GH): Growth hormone is secreted by somatotropes which are the acidophilic cells of anterior pituitary.It...

Lecture 3 Dep. of Medical Physiology Dr.HananAltaee Growth hormone (GH): Growth hormone is secreted by somatotropes which are the acidophilic cells of anterior pituitary.It is protein in nature, having a single-chain polypeptide with 191 amino acids and molecular weight of 21,500. Basal level of GH concentration measured by radioimmunoassay in adult humans is normally less than 3 ng/mL; in a child or adolescent, it is about 6 ng/ml. Growth hormone is transported in blood by GH-binding proteins (GHBPs). Half-life of circulating GH is about 20 minutes. It is degraded in liver and kidney. Action of growth hormone: GH is responsible for the general growth of the body, by increasing cell size (hypertrophy) and promoting mitosis, with development of greater numbers of cells and specific differentiation of certain types of cells such as bone growth cells and muscle cells. Physiological effect of GH: Effect on metabolism GH increases the synthesis of proteins, mobilization of lipids and conservation of carbohydrates (how)?? 1Page A. On protein metabolism: GH accelerates the synthesis of proteins by: i. Increasing amino acid transport through cell membrane. ii. Increasing ribonucleic acid (RNA) translation. iii. Increasing transcription of DNA to RNA.  iv. Decreasing catabolism of protein. v. Promoting anabolism of proteins indirectly:?? GH increases the release of insulin (from β-cells of islets in pancreas), which has anabolic effect on proteins. B. On fat metabolism: GH mobilizes fats from adipose tissue. These fatty acids are used for the production of energy by the cells, thus the proteins are spared. Above physiological level of GH, lot of acetoacetic acid from liver is released into the body fluids, leading to ketosis. C. On carbohydrate metabolism: i. Major action of GH on carbohydrates is the conservation of glucose (Decrease in the peripheral utilization of glucose for the production of energy). ii. Increase in the deposition of glycogen in the cells. iii. Decrease in the uptake of glucose by the cells (Diabetogenic effect). Hypersecretion of GH increases blood glucose level enormously & will cause continuous stimulation of the β-cell in the islets of Langerhans in pancreas and increase in secretion of insulin. Effect on bone: In embryonic stage, GH is responsible for the differentiation and development of bone cells. In later stages, GH increases the growth of the skeleton. It increases both the length as well as the thickness of the bones.?? GH increases: 2Page i. Synthesis and deposition of proteins by chondrocytes and osteogenic cells. ii. Multiplication of chondrocytes and osteogenic cells. iii. Formation of new bones by converting chondrocytes into osteogenic cells.  iv. Availability of calcium for mineralization of bone matrix by enhancing the intestinal calcium absorption. GH increases the length of the bones, until epiphysis fuses with shaft, which occurs at the time of puberty. After the epiphyseal fusion, length of the bones cannot be increased. However, it stimulates the osteoblasts strongly. So, the bone continues to grow in thickness throughout the life. Particularly, the membranous bones such as the jaw bone and the skull bones become thicker under the influence of GH. GH acts on bones, growth and protein metabolism through somatomedin (what is this)? GH stimulates the liver to secrete somatomedin, which is defined as a substance through which growth hormone acts. It is a polypeptide with the molecular weight of about 7,500. Somatomedins(insulin-like growth factor) are of two types: 1. Insulin-like growth factor-I (IGF-I), which is also called somatomedin C acts on the bones and protein metabolism. The somatomedin C binds with plasma proteins very strongly. Because of this, the molecules of somatomedin C are released slowly from the plasma proteins. Thus, it can act continuously for a longer duration. The action of somatomedin C lasts for about 20 hours. Somatomedin C acts through the second messenger called cyclic AMP 2. Insulin-like growth factor-II plays an important role in the growth of fetus. Effect on electrolytes: GH decreases the elimination of electrolytes from the body. These electrolytes will be diverted from the blood to the tissues for their growth. 3Page GH also  Increases muscle mass through sarcomere hypertrophy.  Stimulates the growth of all internal organs excluding the brain.  Plays a role in homeostasis.  Stimulates the immune system.  Increases deiodination of T4 to T3.  Growth hormone receptor. GH receptor is a transmembrane receptor. GH binds with the receptor situated mainly in liver cells and forms the hormone receptor complex which induces somatomedin secretion. Somatomedin in turn, executes the actions of growth hormone. Regulation of GH Secretion. Growth hormone secretion is altered by various factors, however, hypothalamus and feedback mechanism play an important role in the regulation of GH secretion. GH secretion is stimulated by:  Hypoglycemia.  Fasting.  Starvation.  Exercise.  Stress and trauma.  Initial stages of sleep. (Nearly fifty percent of GH secretion occurs during the third and fourth NREM sleep stages (Non rapid eye movement sleep), figure1. 4Page Figure 1 GH secretion is inhibited by:  Hyperglycemia.  Increase in free fatty acids in blood.  Later stages of sleep.  Role of hypothalamus in the secretion of GH: Hypothalamus regulates GH secretion via three hormones 1. Growth hormone-releasing hormone (GHRH)It increases the GH secretion by stimulating the somatotropes of anterior pituitary. 2. Growth hormone-releasing polypeptide (GHRP): Itincreases the release of GHRH from hypothalamus and GH from pituitary. 3. Growth hormone-inhibitory hormone (GHIH) or somatostatin: It decreases the GH secretion. Somatostatin is also secreted by delta cells of islets of Langerhans in pancreas. These three hormones are transported from hypothalamus to anterior pituitary by hypothalamo hypophyseal portal blood vessels.(figure 2). Figure 2 5Page APPLEID PHYSIOLOGY: Gigantism: Hypersecretion of GH in childhood or in pre-adult life before the fusion of epiphysis of bone with shaft, mostly due to Tumor of acidophil cells in the anterior pituitary. Signs and symptoms:  General overgrowth of the person leads to the development of a huge stature, with a height of more than 7 or 8 feet. The limbs are disproportionately long, hyperglycemic and they develop glycosuria and pituitary diabetes or diabetes mellitus is developed, they may have visual impairment. Acromegaly: Hypersecretion of GH in adults after the fusion of epiphysis with shaft of the bone. Acromegaly is the disorder characterized by the enlargement, thickening and broadening of bones, particularly in the extremities of the body.The cause may be Tumor of acidophilcells in the anterior pituitary. Signs and symptoms: Acromegalic or gorilla face: Face with rough features such as protrusion of supraorbital ridges, broadening of nose, thickening of lips,thickening and wrinkles formation on forehead and prognathism (protrusion of lower jaw) , enlargement of hands and feet, Kyphosis (extreme curvature of upper back thoracic spine). Accompanying problems can include sweating, pressure on nerves (e.g., carpal tunnel syndrome), muscle weakness, excess sex hormone-binding globulin (SHBG), insulin resistance or even a rare form of type II diabetes, and reduced sexual function. Enlargement of visceral organs such as lungs thymus, heart, liver and spleen. Hyperactivity of thyroid, parathyroid and adrenal glands, Hypertension. Headache Visual disturbance (bitemporal hemianopia). Surgical removal is the usual treatment for GH-producing tumors. somatostatin agonist and bromocriptine (dopamine agonist) can be used to block GH secretion because both somatostatin and dopamine 6Page negatively inhibit GHRH-mediated GH release from the anterior pituitary.  Hypoactivity of anterior pituitary Dwarfism: Dwarfism is a pituitary disorder in children, characterized by the stunted growth. Causes Reduction in GH secretion in infancy or early childhood  Tumor of chromophobes: It is a non-functioning tumor, which compresses and destroys the normal cells secreting GH. It is the most common cause for hyposecretion of GH, leading to dwarfism  Panhypopituitarism: In this condition, there is reduction in the 7Page secretion of all the hormones of anterior pituitary gland.This type of dwarfism is associated with other symptoms due to the deficiency of other anterior pituitary hormones Signs and symptoms: The maximum height of anterior pituitary dwarf at the adult age is only about 3 feet but the proportions of different parts of the body are almost normal.  Only the head becomes slightly larger in relation to the body, their mental activity is normal with no mental retardation. Reproductive function is not affected, if there is only GH deficiency. Diagnosis of GH deficiency involves a multiple-step diagnostic process, usually culminating in GH stimulation tests to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli. Pituitary insufficiency is accompanied by atrophy of the adrenal cortex, sensitivity to stress, growth inhibition, depressed thyroid function, hypoglycemia, pallor, and atrophy of the gonads. Pituitary insufficiency may be caused by tumors or, in women, by infarction following shock due to postpartum hemorrhage. https://synapse.koreamed.org/upload/synapsedata/pdfdata/2074wjmh/wjmh-37-19.pdf Summary  The pituitary gland consists of two functional sections in humans: the anterior 8Page lobe, which secretes mainly tropic hormones; and the posterior lobe, which contains nerve endings that project from the hypothalamus and release oxytocin and vasopressin  The pituitary plays a critical role in regulating the function of downstream glands, and also exerts independent endocrine actions on a wide variety of peripheral organs and tissues.  The pituitary also supplies hormones that regulate reproductive tissues and lactation—FSH, LH, and prolactin. Prolactin, in particular, is regulated by many of the factors that also regulate growth hormone secretion, although specific regulators may have opposing effects.   Growth hormone is synthesized by somatotropes. It is secreted in an episodic manner in response to hypothalamic factors, and secretion is subject to feedback inhibition.  Growth hormone activates growth and influences protein, carbohydrate, and fat metabolism to react to stressful conditions.  Many, but not all, of the peripheral actions of growth hormone can be attributed to its ability to stimulate production of IGF-I.  Growth reflects a complex interplay of growth hormone, IGF-I, and many other hormones.  The consequences of overproduction or underproduction of such influences depends on whether this occurs before or after puberty. Deficiencies in components of the growth hormone pathway in childhood lead to dwarfism; overproduction results in gigantism, acromegaly. Case study: A 7-year-old boy is evaluated for short stature. His average circulating growth hormone level is within the normal range for his age, but levels of IGF-I are reduced. What do you think His growth failure is due? 9Page