Growth Hormone

1. What cells synthesize/release GH?

2. What are the Effects of GH?

Somatotrophs in the AP produce growth hormone (somatotropin)

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Effects:

• Increased size/# of cells/ mitosis

• Specific differentiation

Describe the Difference between GHRH and Somatotropin

Hypothalamus stimulates GH secretion from somatotroph via growth hormone releasing hormone (GHRH)

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Hypothalamus inhibits GH synthesis and release from somatotroph via somatostatin

Draw out the pathway of GH and SomatoStatin

• Starting From the hypothalamus and ending at the effector organs

  • (Adipose, Muscle, Hepatocyte, and other effectors)

• Include the Physical Conditions in which GH will be stimulated to release

• Include the Negative Feedback Mechanisms

Describe the Negative Feedback in the GH pathway

Negative Feedback on GH pathway

• Long Loop (IGF-1): 

  • Inhibits GH production from Somatotrophs 

  • Inhibits GHRH release from arcuate nucleus in hypothalamus

  • Stimulates secretion of Somatostatin from periventricular nuclei

• Short Loop (GH):

  • inhibits GH release from Somatotrophs

1. When is GH released throughout the day?

2. Why is IGF-1 a better indicator of GH Secretion?

3. Draw out a graph depicting Bursts of GH throughout the Day

GH is released primarily during slow wave sleep

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IGF-1 is a better indicator because:

• regulated by GH

• Longer Circulating Half-Life

1. What is the main target of GH and what is GH’s Action?

2. What happen to 50% of GH? Why is this beneficial?

Liver:

• GH’s main target = Liver → stimulates production of insulin-like growth factor (IGF-1)

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GHBP:

• 50% of GH is bound to GH-binding protein (GHBP)

• Increases Half-Life of GH

• Make it less available for degradation by Liver/Kidney

Draw out the graph of GH Secretion during lifespan

What does Peak Height Correspond with?

1. What is the most biologically active somatomedin?

   • Where is this molecule Secreted from?

   • What is its general function?

   • What are the effects of this molecules?

IGF-1:

• most biologically active somatomedin is IGF-1 or Somatomedin C

• mainly secreted from the liver after stimulation by GH

• Has Insulin-Like Effects → promotes fuel storage in various tissues

• Inhibits GH and GHRH secretion

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Effects:

• Stimulates the growth of bones, cartilage, and soft tissue

• stimulates osteoblast replication and collagen/bone matrix synthesis

• Regulates metabolism of chondrocytes

• mitogenic (stimulates DNA, RNA, and protein synthesis)

1. Describe the the Effect of GH and IGF-1 on Bone Growth

2. How does GH fail?

Bone Growth:

• Increases growth of skeletal frame:

  • Increases deposition of protein by chondrocytic and osteogenic cells

  • Increases rate of reproduction of these cells

  • Increases rate chondrocytes → osteogenic cells

• Long bones grow in length at the epiphyseal cartilages

• stimulates osteoblasts

  • Osteoblasts in bone periosteum deposit new bone on the surfaces of older bone

    • Osteoclasts remove old bone

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Failure:

GH Fails w/o insulin and carbohydrates

• needed for energy and enhanced AA and glucose transport

1. What type of hormone is GH? What does it activates?

   • What are its general Metabolic Effects?

   • How can GH cause diabetes?

2. Describe the Specific Metabolic Actions that GH has on:

   • Adipose Tissue

   • Skeletal Muscles

   • Liver

GH = Anabolic/Lipolytic Hormone

• activates hormone sensitive lipase and mobilizes fats from adipose.

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General Metabolic Effects:

• counteracts the action of insulin on lipid and glucose metabolism

  • decreases skeletal muscle glucose utilization

  • Stimulates Lipolysis/ hepatic glucose production

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GH can cause DIabetes b/c it:

• Decreases carbohydrate utilization

• Hyperglycemic effects b/c:

  • decreased glucose uptake

  • increased glucose production (by liver)

  • Increases FFA oxidation = stimulate GNG

• This increases Insulin Levels (in order to maintain normal glucose levels) → Insulin resistance

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Adipose:

• Stimulates Release and Oxidation of FFA

  • mediated by regulating the activity of
    lipoprotein lipase

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Skeletal Muscles:

• decreases skeletal muscle glucose utilization

• stimulates amino acid uptake and incorporation into protein

• suppression of protein degradation

• cell proliferation

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Liver:

• stimulates hepatic IGF-1 production and release

• promotes GNG and reduces glucose uptake

  • Net result = stimulating hepatic glucose output

Describe the interaction of nutrient, GH, and IGF-1 when the pt has:

• ample nutrient?

• High Calories, low AA

• Fasting (or low nutrient availble)

Ample nutrients:

• Amino acids increase GH and insulin

• High serum glu increases insulin secretion

• High GH, insulin and nutrients promote growth

High calories, low amino acids:

• High carbs increases insulin secretion

• But low amino acid inhibits GH and IGF production

• Dietary carbs and fats used for energy but not good conditions for growth

Fasting, overall low nutrient availability:

• Low carbs and fats increase GH levels and lower insulin levels, however IGF levels are low, conditions do not favor growth.

• GH is beneficial because it promotes fat mobilization while attempting to minimize tissue protein loss.

• With less insulin, peripheral tissue glucose use is decreased, sparring glucose for essential tissues such as brain

List out the Stimulating and Inhibiting Factors of GH Secretion

1. How can Dwarfism occur?

2. Describe the etiology of Laron Dwarfism

3. What happens if there’s a deficiet in GH secretion after growth plate 

Dwarfism:

• If GH Deficiency developed before puberty

• Many cases derived from panhypopituitarism

  • All Anterior Pit. Hormones deficient

  • not mature sexually and infertile

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Laron Dwarfism:

• GH secretion is normal or high

• Receptor defective so liver does not produce IGF-1

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If GH Deficiency At Adulthood:

• At this point, Growthplate (epiphyses) has close

• Causes Hypoglycemia

Differentiate between Gigantism and Acromegaly

Gigantism:

• Hypersecretion of GH in children and adolescents

• Increased bone length/thickness

Acromegaly:

• Hypersecretion of GH during adulthood

• enlargement of the hands and feet, coarsening of
  facial features, insulin resistance, and diabetes

Describe how hyper GH can cause pituitary diaabetes

Pituitary Diabetes:

• lipolysis and decreased glucose uptake → high blood glucose → high Insulin Secretion (Type II) → Burn out of B-cells (Type 1)