Metabolic Actions. Salam AWN :D

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2 Salam AWN :D this lecture is so easy, many concepts are repeated over and over here.. slides for this lec are [34 53] I included all of them except for : 34, 36, 37, 41, 47 so please read those specific slides. LET'S BEGIN Growth Hormone (GH) has : 1- Growth effects. 2- Metabolic effects. Will be illustrated now Metabolic Actions liver Muscles Adipose tissue increase gluconeo genisis increase formatio n of RNA, Protiens decrease glucose uptake increase lean body mass decrease glucose uptake increase lipolysis P a g e 2

3 LIVER : -GH increases Gluconeogenesis. (formation of glucose from Non- carbohydrate substances) - GH increases RNA & Protein synthesis. (giving growth effects) MUSCLES : -GH decreases Glucose uptake. -GH increases lean body mass. (this is imp in young ppl, and that's why elderly will have low lean body mass & more adipose tissue) ADIPOSE TISSUE: -GH decreases glucose uptake -GH increases lipolysis & decreases adiposity General information about GH : -It affects bones, heart and lungs and increases their growth and function. -It increases linear growth by affecting chondrocytes. -It uses/ utilizes FAT as a source of energy. {lypolytic} -It spares/ deposits GLUCOSE & PROTIENS. This is extremely imp -It has an Anti-Insulin effect. GH acts opposite to insulin -It is a hyperglycemic hormone. (major 4 hormones : GH, Glucagon, Cortisole imp role in fasting-, Epinephrine and to some extent oxytosine.. all have hyperglycemic effects, so whenever Glucose levels In blood decreases, theses hormones will act to increase it). -It is a carbohydrate and protein sparing hormone. To summarize the metabolic effects of GH : 1. Protein metabolism: Anabolic (synthsis) rate of protein synthesis in all cells. 2. Fat metabolism: Catabolic (opposite to synthesis) / lipolytic P a g e 3

4 mobilization of free fatty acids from adipose tissue stores to provide energy. 3. Carbohydrate metabolism: Hyperglycemic rate of glucose utilization throughout the body & glucose uptake by cells. GH enhances body protein, uses fat stores (lipolytic), & conserves carbohydrates GH Promotes Protein Deposition (anabolism) in Tissues. (Building up more intracelluler protiens + Decreasing catabolism of protiens) : 1- Enhancement of Amino Acid Transport through the Cell Membranes. 2- Increased Nuclear Transcription of DNA to Form RNA. (May be the most important function of GH). 3- Enhancement of RNA Translation to Cause Protein Synthesis by the Ribosomes (can begin in minutes). 4- Decreased Catabolism of Protein and Amino Acids. (Protein sparer). P a g e 4

5 GH Enhances Fat Utilization for Energy first of all, this part was not fully understood in the lec, but here is all what we got: - lipolytic means utilizing or using free fatty acids in order to get energy. Since GH is a lipolytoc hormone, it will increase the activity of hormone sensitive lipase (HSL), and will decrease the activity of lipoprotiene lipase (LPL). - Role of LPL: get fatty acids from circulation to give you neutralized substances called "triglyceride". And this enzyme is present in the endothelial cells related to chylomicrons. - Role of HSL: uses neutral fat as a source of energy. This enzyme is located in adipose tissue. -insulin has the exact opposite effect of GH.( insulin decreases HSL) -GH has a ketogenic effect : increases formation of keton bodies (acetone, acetoacitic acid & beta hydroxybutyric acid). Ketogenic" Effect of Excessive Growth Hormone mobilization from adipose tissue large quantities of acetoacetic acid are formed by the liver and released into the body fluids, (could cause fatty liver). P a g e 5

6 **GH Enhances release of fatty acids from adipose tissue (requires several hours). ** GH Enhances the conversion of fatty acids to acetyl coenzyme A (acetyl-coa) and its subsequent utilization for energy (krebs cycle), The lipolytic effects are at least partly mediated via the hormonesensitive lipase. GH depresses the lipoprotein lipase (LPL) activity. GH Decreases Carbohydrate Utilization Mainly due to GH-induced insulin resistance 1- Decreased glucose uptake in tissues such as skeletal muscle and fat. 2- Increased glucose production by the liver. 3- Increased insulin secretion (compensatory increase due to increased blood glucose levels). This is an indirect way. So we conclude that: -GH is an insulin resistant hormone (anti-insulin) -GH has a hyperglycemic effect. -GH is a counter regulatory hormone. RESULT : GH has a diapetogenic effect (will induce diabetes.. this type is called : pituatery diapetes) P a g e 6

7 Characteristically increases during the first 2 hours of deep sleep Life-long GH secretion, decreases slowly with aging, finally falling to about 25% of the adolescent level in very old age. Regulation of GH Secretion Secreted in a pulsatile pattern It is the amplitude,and not the frequency, of the pulsatile release that is changed. increases during excersise Note : regarding elderly, the Frequency of GH secretion is P a g e 7

8 Not changed, but the amplitude is decreased. Effect of Protein Deficiency on GH Levels: The major long-term controller of growth hormone secretion is the long-term state of: nutrition (e.g: hypoglycemia or protein deficiency) of the tissues themselves, especially their level of protein nutrition. Nutritional deficiency or excess tissue need for cellular proteins - e.g., exercise - in some way increases the rate of GH secretion. GH, in turn, promotes synthesis of new proteins, while at the same time conserving the proteins already present in the cells. This figure shows one type of protein deficiencies in children called "Kwashiorkor".. Try to spell it XD As a result, GH levels will rise. **If we try to give the patient carbohydrates as a treatment, the levels of GH will still be up! So we did not treat the patient. **If we give him Protein treatment, GH levels will fall down good treatment. RULE: Under severe conditions of protein malnutrition, adequate calories alone are not sufficient to correct the excess production of GH. P a g e 8

9 GH & Aging : As one ages, the average plasma concentration of GH in a normal person gradually decreases Age-related fall in the GH levels is associated with reduction in the hypothalamic GHRH response/ hypersecretion of somatostatin. GH secretion accelerates aging features The aging effects of GH deficiency: decreased protein deposition (decreased lean body mass) increased fat deposition (increased adipose tissue :') ) Effects: -increased wrinkling of the skin. -increased Cardiovascular morbidity. -diminished muscle mass and strength. -feeling of decreased energy & physical drive. P a g e 9

10 Good Summery : If GH increases in children Giantism. if GH increases in adults Acromegaly. if GH decrease in children Dwarfism. if GH decreases in adults "GH deficiency in adults disease".. will be treated also. Regulation of Growth Hormone Secretion: **GH secretion controlled primarily by: 1- hypothalamic GHRH stimulation (ventromedial nucleus). 2- somatostatin inhibition **Neurotransmitters are involved in control of GH secretion via regulation of GHRH and somatostatin. **Neurotransmitter systems that stimulate GHRH and/or inhibit somatostatin : Catecholamines acting via a2-adrenergic receptors. 2- Dopamine acting via D1 or D2 receptors. 3- Excitatory amino acids (glutamate, glycine) acting via both (N-methyl-D-aspartate) NMDA and non-nmda receptors. **Bate-adrenergic receptors stimulate somatostatin release and inhibit GH. (Direct way) **Beta-adrenergic receptors inhibit hypothalamic release of GHRH. (indirect way) P a g e 10

11 The previous pic is extremely IMP, and a question will 100% come from it, as the doctor said. case : if a child came with a 4 nano gram concentration of GH (NORMAL= 5), we should start giving him one of the "stimulating factors" mentioned previously, & then if GH reaches to the normal levels this would be great. conclusion : do not give a patient GH immediately as a treatment, instead, give one of the stimulating factors. Abnormalities of GH secretion : **Dwarfism : GH secretion during childhood. Stunted physical growth, Normal mentality **Giantism: GH secretion during childhood **Acromegaly (Acro :pirepheral parts of body, Megaly: enlargement or hypertrophy): GH secretion during adulthood. Acidophilic tumor occurs after adolescence, after the closure of epiphyseal plates, the shafts of the bones cannot P a g e 11

12 grow taller, but the bones can become thicker and the soft tissues can continue to grow. Important que : what is the only hormone which causes dwarfism + mental retardation when it is deficient? Thyroxine. So the next pic illustrates that def. in GH will not cause mental retardation, but def. in thyroxine will. so here the difference between the second and third child, is that the second has mental retardation (hypothyroid), and the third child is well mentally. P a g e 12

13 **This is the same person! but the change happened gradually and it was unnoticed. **the patient didn't get taller. P a g e 13

14 Study the clinical features of Acromegaly case in the previous pic. Prognathism : protrusion of the lower jaw. Visual field changes : because of the tumor found in the brain sella turcica is creating a pressure optic nerves. Doctor asks you to look for hirstiusm, gynesomastia and lactation causes. Hands and Feet enlargment : effects on membranous bone, cartilage and soft tissues as skin. Osteoarthritis : excess growth of vertebrae, bcz they are membranous further Clinical features of acromegaly : Local tumor effects piuitary, visual field defects, headache Somatic systems Acral enlargement, prognathism, carpal tunnel syndrome Enlargement of membranous bones including cranium, nose, forehead bones, supraorbital ridges. Hunched back (kyphosis) (enlargement of vertebrae). CV system P a g e 14

15 Ventricular hypertrophy, cardiomyopathy, HT, HF Pulmonary system Sleep disturbances, sleep apnea Visceromegaly (enlargement of organs) Tongue, thyroid gland, liver, spleen, liver, kidney, prostate Metabolic Insulin resistance, fasting hyperglycemia. last note : All hormones are lipolytic, except for Insulin (which is a lipogenic hormone).. so Insulin causes hypoglycemia & build up fat. So patients taking insulin shouldn't take overdoses of it, cause they will be building up fat! ويعطيكم العافية ^_^ زميلتكم تمارة عالونة P a g e 15