Physiology T3: Growth Hormone
What is the underlying cause of John's condition? A. Excess secretion of growth hormone postpuberty B. Excess production of androgens postpuberty C. Insufficient production of beta -estradiol D. Excess production of glucocorticoids
A
What are the characteristics of the insulin-like growth factor (IGF-1)?
Anabolic - skeletal muscle hypertrophy Protective for cartilage cells Activation of osteocytes - anabolic factor for bone Neurotrophic factor - survival of neurons
What has a significant effect on GH production?
Body composition
Growth hormone fails to cause growth if ______ are excluded from the diet?
Carbohydrates —fails to cause growth in animals that lack a pancreas
How does GH promote linear growth?
GH stimulates the epiphyseal cartilage Chondrocytes in the growth plate are stimulated by GH, leading to proliferation of these cells and deposition of new cartilage, followed by conversion of this cartilage to bone GH also increases osteoblasts activity, total bone mass is increased by GH even after epiphyseal closure
What regulates the magnitude of the GH release during GH secretion?
GHRH
What does the GH impair that gets uptaken into adipose cell?
Glucose
What uptake does GH induce?
Glucose and amino acid Simulates protein synthesis Possible using the energy derived from its lipolytic activity
What is HIIT?
High intensity interval training - exercise performed at an all out effort, followed by a recovery phase of rest or low intensity exercise
What stimulates osteoblast and chondrocyte activity to increase bone growth?
IGF-1
What is the primary signal for resistance exercise-induced protein synthesis?
Mechanical stretch (force) applied to the muscle during weight lifting
What is IGF-1 similar to?
Molecular structure to insulin
What happens to GH when someone is obesity ?
Reduced mean GH concentrations, associated with decreased pulsatile GH secretion and a shorter GH half-life
What do osteoclasts do?
Remove old bone
What does exercise induced mechanical stretch trigger?
Secondary signal of IGF-1 synthesis and the cascade of downstream signaling events leading to increased protein synthesis
Growth hormone promotes growth of many body tissues such as?
Skeletal muscle Bone
What does the GH cause the liver to form?
Somatomedins
How do GH and IGF-1 provide a negative feedback loop for GH?
Stimulate the secretion of somatostatin by the hypothalamus
How is the GH effected at early childhood?
The rate of secretion increases steadily from birth into early childhood During childhood, secretion remains relatively stable
How is the GH effected during puberty?
There is an enormous secretory burst that induces in females by estrogen and in males by testosterone
True or false: GH is secreted throughout life?
True
When is growth hormone secretion reduced?
With age in normal subjects
When is the largest secretory burst of your GH?
Within 1 hour of falling asleep
All of the following stimuli increase GH secretion EXCEPT: A. Fasting or chronic protein deprivation B. Strenuous exercise C. Release of ghrelin D. Increased secretion of somatostatin
D
Regarding the metabolic actions of growth hormone, which of the following is INCORRECT? A. Growth hormone inhibits glucose uptake into muscle B. Growth hormone stimulates gluconeogenesis in liver. C. The actions of growth hormone are the opposite of those of insulin D. Growth hormone promotes the storage of lipid in adipose tissue
D
The major targets of growth hormone are ________. A. the blood vessels B. the adrenal glands C. the kidney D. bones and skeletal muscles
D
How are growth hormone and body composition related?
Decline in lean body mass In increase in relative ADI position/overt obesity — negative determinant of GH secretion in all age groups
What factors stimulate growth hormone secretion?
Decreased blood glucose Decreased blood free fatty acids Starvation or fasting, protein deficiency Trauma, stress, excitement Exercise Testosterone, estrogen Deep sleep Growth hormone releasing hormone
What happens when GH decreases carbohydrate utilization?
Decreased glucose uptake in tissues such as skeletal muscle and fat Increased glucose production by the liver - glycogen Increased insulin secretion
What do intermittent fasting protocols have?
Demonstrated elevated levels of GH
What is GH induced insulin resistance?
Diabetogenic
What is REM sleep?
(Rapid eye movement sleep) Brain waves mimic activity during the waking state The eyes remain closed but move rapidly from side- to -side, perhaps related to the intense dream and brain activity that occurs during this stage
What is necessary for growth hormone to be effective?
Adequate insulin activity Adequate availability of carbohydrates **insulin —> enhance the transport of some amino acids into cells
Growth hormones act indirectly to induce anabolic effects in bone and muscle. What then acts directly to make these tissues grow? A. Growth hormone stimulates the liver to release a growth factor called IGF-1 B. Growth hormone stimulates androgen secretion from the adrenal cortex C. Growth hormone increases amino acid absorption from the digestive tract. D. Growth hormone increases cellular calcium storage.
A
What contributes significantly to predict changes in GH secretion?
Abdominal adiposity Physical fitness, rather than age
What is gigantism?
Accelerated linear growth of skeleton Occurs during childhood Adenoma
What is IGF capable of at high concentrations?
Activating the insulin receptor, it can also complement for the effects of insulin
Which one of the following statements regarding IGF-1 is INCORRECT? A. IGF-1 stimulates osteoblast and chondrocyte activity to increase bone growth. B. IGF-1 is produced primarily by the liver C. IGF-1 also plays a major role in muscle growth D. IGF-1 increases breakdown and release of lipids
All answers are correct
What does the promotion of fat utilization for energy (lipolytic effect) increase?
Amino acid uptake in skeletal muscle
How does the growth hormone effect the promotion of protein deposition in tissues?
Anabolic hormone Increases amino acid uptake in most cells and synthesis of amino acids into proteins
What is acromegaly?
Appears in adulthood/ late adolescence Changes in facial features/ hands and feet Internal organs are of increased size
Bone, muscle and adipose tissue are target tissue for: A. Calcitonin B. Growth hormone C. Aldosterone D. Follicle stimulating hormone
B
On a daily basis, growth hormone is released in a pulsatile fashion. In a given 24 hour period, the greatest release of growth hormone occurs: A. In the morning, one hour before rising B. Within 1 hour of falling asleep. C. Midday (around noon) D. During REM sleep
B
Over the course of a lifetime, secretion of growth hormone is greatest during: A. Childhood B. Puberty C. Birth D. Senescence
B
Patients diagnosed with acromegaly do not exhibit increased linear growth of their long bones. The reason for this is: A. Acromegaly is diagnosed before a patient has been through puberty. B. After puberty, the epiphyseal plates are already closed. C. Acromegaly only affects skeletal muscle. D. Elevated growth hormone increases lipid breakdown which affects bone marrow
B
A 35-year-old major league baseball player starts taking human growth hormone to increase his performance. Which of the following best describes an effect of human growth hormone? A. It decreases lipolysis. B. It has a long half-life. C. It inhibits protein synthesis. D. It stimulates production of insulin-like growth factors by the liver
D
What is the GH ketogenic?
Because GH increases plasma levels of free fatty acids and ketoacids
What is the diabetogenic affect?
Blood glucose concentration tends to rise and insulin secretion increases to compensate for the GH induced insulin resistance
John is a 26-year-old man who begins to notice a progressive enlargement of feet, hands, cranium, nose, and lower jaw bone. His doctor recommends irradiation of the pituitary gland. What is the most likely diagnosis? A. Gigantism B. Cretinism C. Acromegaly D. Turner's syndrome
C
Which of the following is NOT an effect of growth hormone (GH)? A. Promotes bone growth. B. Promotes muscle growth. C. Causes lipid accumulation within adipocytes. D. Promotes amino acid uptake by cells.
C
What does IGF-1 play an important role in?
Childhood growth and continues to have anabolic effects in adults
What coordinates the availability of nutrients with anabolism and either caloric storage or mobilization?
Complementary regulation of GH and insulin secretion
When is GH secretion highest?
During puberty
Hypersecretion of growth hormone A. results in gigantism if it occurs in children. B. causes acromegaly in adults. C. increases the probability that a person will develop diabetes. D. can lead to severe atherosclerosis. E. All of these are correct
E
How does GH promote protein deposition in tissues?
Enhancement of amino acid transport through the cell membranes Enhancement of RNA translation to cause protein synthesis by the ribosomes Increased nuclear transcription of DNA to form RNA Decreased catabolism of protein and amino acids (protein sparer- mobilization of FFA)
What are symptoms of acromegaly?
Enlarged hands and feet Coarsened, enlarged facial features Coarse, oily, thickened skin Excessive sweating and body odor Fatigue and muscle weakness Severe snoring A deepened, husky voice Impaired vision Headaches Enlarged tongue Pain and limited joint mobility Menstrual cycle irregularities in women Erectile dysfunction in men Enlarged organs, such as the heart Loss of interest in sex Prominent jaw line Enlarged brow Thickening of bone
What is the ketogenic effect of excessive GH?
Excessive amounts of GH —> fat mobilization from adipose tissue Sometimes large quantities of acetoacetic acid are formed by the liver and released into the body fluids, thus causing ketosis
What is a robust stimulus of GH secretion?
Exercise —potent physiological stimulus for GH secretion, and both aerobic and resistance exercise result in significant, acute increases in GH secretion
How is the growth hormone effect on the impairment of carbohydrate utilization for energy and regulation of blood glucose related?
Exerts anti-insulin effect by suppressing insulin's ability to promote glucose uptake in the peripheral tissues
When do GH levels increase?
Fasted state
What are stimuli that increase GH secretion?
Fasting, chronic protein deprivation - other conditions in which there is an acute fall in plasma levels of metabolic substances such as glucose and free fatty acids Increased plasma levels of amino acids - such as occur after a protein meal Exercise and stressful stimuli
What is used for energy in preference to use of carbs and proteins?
Fat
What does excessive amounts of GH lead to?
Fat mobilization from adipose tissue
How has GH been incorporated into performance enhancing effects?
First promoted in lay publications, long before scientists fully acknowledged its benefits Athletes that have used GH to enhance their athletic performance and to accelerate the healing of sporting injuries
What are the 3 negative feedback loops for GH?
GH IGF-1 GH and IGF-1
How does the growth hormone affect the promotion of fat utilization for energy?
GH causes the mobilization of fatty acids form adipose tissue and the preferential utilization of free fatty acids for energy (lipolytic effects)
How does the growth hormone effect the impairment of carbohydrate utilization for energy?
GH decreases the uptake and utilization of glucose by many insulin-sensitive cells, such as muscle and adipose tissue
What happens to GH during HIIT?
GH levels rise significantly only with high intensity exercise that taps into the anaerobic energy system In one study, a minimum of 10 minutes of high intensity exercise was needed to increase growth hormone levels Low intensity exercise has no effect on growth hormone
How is GH effected after early adulthood?
GH production starts to decline at a rate of ~14% per decade of adult life
What are the major regulatory factors of growth hormone secretion?
GH releasing hormone (GHRH) Somatostatin (growth hormone inhibiting hormone ) Growth hormone (negative feedback) Insulin like growth factor -liver
What type of hormone is GH classified as?
Hyperglycemic hormone —acute hypoglycemia is a stimulus for GH secretion
GH stimulates production of?
IGF-1
What promotes the differentiation and proliferation of a type of progenitor cell called a myoblast that gives rise to muscle cell?
IGF-1
When is GH secretion decreasing?
In adult life
What is osteoblasts job?
In the bone periosteum and in deposit new bone not the surfaces of older bone
What does the action of the GH with its protein anabolic effects produces what?
Increase in lean body mass
What factors inhibit growth hormone secretion?
Increased blood glucose Increased blood free fatty acids Aging Obesity Growth hormone inhibitory hormone (somatostatin) Growth hormone (exogenous) Somatomedins (insulin like growth factor)
How does GH effect the bone and cartilage?
Increased deposition of protein by the chondrocytes and osteogenic cells Increased rate of reproduction of these cells A specific effect of converting chondrocytes into osteogenic cells, thus causing deposition of new bone
What are the growth hormones metabolic effects on the body?
Increased rate of protein synthesis in most cells of the body Increased mobilization of fatty acids from adipose tissue, increased free fatty acids in the blood, and increased use of fatty acids for energy Decreased rate of glucose utilization throughout the body GH enhances body protein, decreases fat stores, and conserves carbohydrates
Growth hormone A. increases the usage of glucose. B. increases the breakdown of lipids. C. decreases the synthesis of proteins. D. decreases the synthesis of glycogen. E. All of these are correct
Increases the synthesis of proteins
When do excessive levels of insulin appear?
Inhibit GH secretion, through enhanced negative feedback inhibition by IGF-1
How is IGF-1 a negative feedback loop for GH?
Inhibit secretion of GH by the anterior pituitary
How is GH a negative feedback loop for GH?
Inhibits secretion of GH by the anterior pituitary
What are somatomedins also called and why?
Insulin like growth factors (IGFs) Because many of the somatomedins effects on growth are similar to the effects of insulin on growth
What is IGF-1 produced by?
Liver
What is reduced when GH and IGF-1 production are reduced?
Muscle mass and protein synthesis are reduced
GH is classified as one of the stress hormones and is increased by what?
Neurogenic stress Physical stress —it promotes lipolysis, increases protein synthesis, and antagonizes the ability of insulin to reduce blood glucose levels
Does the growth hormone function through a specific target gland?
No- the growth hormone does not function through a specific target gland but exerts its effects directly on all or almost all tissues of the body
What is the peak response of GH secretion to GHRH reduced in?
Obese subjects and this is reversible with fasting or weight loss
What can induce hyperinsulinemia?
Obesity
What does the GH strongly stimulate in bone growth?
Osteoblasts
What are the growth hormones effects on the body?
Promotion of linear growth Promotion of protein deposition in tissues Promotion of fat utilization for energy Inhibits actions of insulin - impairment of carbohydrate utilization for energy Growth hormone has profound effects on protein, carbohydrate, and fat metabolism
What type of pattern is the GH secreted in?
Pulsatile pattern — secretion occuring approx every 2 hours
What type of sleep decreases the secretion of GH?
REM sleep
What is greater than resorption of bone?
Rate of deposition —thickness of the bone icnreases
How does the GH enhance fat utilization for energy?
Release of fatty acids from adipose tissue and, therefore, increasing the concentration of fatty acids in body fluids CGH enhances conversion of fatty acids to acetyl coenzyme A (acetyl-CoA) and its subsequent utilization for energy
What does the GH exert much of its effects though intermediate substance called?
Somatomedins
What sets the timing (frequency and duration) of GH secretion?
Somatostatin
In contrast to the other pituitary hormones, which stimulate specific target glands, GH has multiple effects throughout what?
The body