REB 4. Hypothalamus-Pituitary-Target Organ Axes: Feedback Control 2 Flashcards
If there was hypo- or hypersecretion of….it would be primary
If there was hypo- or hypersecretion of….it would be secondary
[1] Anterior Pituitary Cells
[2] Hypophysiotropic Hormones
What is Panhypopituitarism?
it is the decrease in secretion of all the anterior pituitary hormones
What are the causes of Panhypopituitarism?
[1] Congenital
[2] Pituitary Tumour (that destroys gland)
[3] Infarction of Portal Vessels during Pregnancy
- especially, lactotropes can increase in numbers in the pituitary gland, and so the pituitary gland grows, but there is no place for it to grow (since it resides in a bony structure)
What are the causes and symptoms of Panhypopituitary Dwarfism?
Cause: deficiency of anterior pituitary hormones during childhood
Symptoms:
- rate of development greatly decreased
- person never passes through puberty (as they never secrete sufficient quantities of gonadotropic hormones to develop adult sexual functions)
What are the causes, symptoms and treatment of Panhypopituitarism in adults?
Cause: hypothyroidism
Symptoms:
- depressed production of glucocorticoids by adrenal glands
- suppressed secretion of gonadotropic hormones (sexual function is lost)
Treatment: treated with adrenocorticol/thyroid hormones
Although growth hormone is essential for growth, it is not wholly responsible for determining rate and final magnitude of growth, this is dependent on…[4]
[1] Genetic Determination
[2] Adequate Diet
[3] Freedom from Chronic Disease/Stressful Environment
[4] Normal Levels of Growth-Influencing Hormones
- e.g. thyroid hormone + sex hormones
What is the most abundant hormone produced by the anterior pituitary gland?
Growth Hormone
Is growth hormone present in adults in whom growth has CEASED?
Yes. But, GH secretion typically declines after middle age
What is the average plasma concentration of GH in ng/mL for an individual who is between age 5 and 20?
6 ng/mL
What is the average plasma concentration of GH in ng/mL for an individual who is between age 20 and 40?
3 ng/mL
What is the average plasma concentration of GH in ng/mL for an individual who is between age 40 and 70?
1.6 ng/mL
What are the target organs that GH binds to so that it can exert its METABOLIC effects? [3]
[1] Adipose Tissue
[2] Skeletal Muscles
[3] Liver
What are the major METABOLIC effects of GH? [3]
[1] Increases the Mobilization of Fatty Acids from Adipose Tissue
- increase in fatty acids in blood
- increased use of fatty acids for energy (conserves glucose for the brain)
[2] Decreased Rate of Glucose Utilization throughout the Body
- increase in blood glucose by decreasing muscle uptake of glucose
- changes result from GH-induced insulin resistance
- effects termed diabetogenic
- excess GH secretion can produce metabolic distubances very similar to type II diabetes!
[3] Increases the Rate of Protein Synthesis in Most Cells of the Body
OVERALL: it uses up fat, conserves carbohydrates, and increases protein synthesis
What is the main way that GH exerts its growth-promoting actions? Is this direct or indirect?
GH exerts most of its growth-promoting effects by INDIRECTLY stimulating Somatomedins
What are Somatomedins?
Somatomedins are a group of proteins that promote cell growth and division in response to stimulation by growth hormone (GH)
They are structurally and functionally similar to insulin and are called Insulin-Like Growth Factors (IGFs)
What are Insulin-Like Growth Factors (IGFs)?
They are also called Somatomedins and they are structurally and functionally similar to insulin
What is the most important Somatomedin/Insulin-Like Growth Factor?
IGF-1 or Somatomedin C
Where is the major source of IGF-1/Somatomedin C circulating?
in liver - then released into blood ony GH stimulation
*side note: it is also produced by most other tissues, but it is not released into the blood
What is the most obvious effect of GH on the body?
growth of bones
What does GH promote growth of bone in?
*hint: there are 2 factors
[1] Growth of Bone Thickness
[2] Growth of Bone Length
How does GH promote the growth of bone? Briefly explain the process.
- increases deposition of protein by chondrocytic (cartilage cells) and osteogenic (bone cells)
- increases the rate of reproduction of these cells
- stimulates differentiation of chondrocytes (cartilage)
- causes deposition of new bone
How does GH promote the growth of bone in WIDTH?
To grow in thickness, osteoblasts are put to work to add a new layer to the bone
How does GH promote the growth of bone in LENGTH?
To grow in length, it is dependent on cartilage and you need to increase the distance because epiphysis and bone shaft.
At some point, all out cartilage is used up and we can no longer grow (this occurs after puberty)
What are the 2 mechanisms that control GH secretion?
[1] Two Hypothalamic Hypophysiotropic Hormones
(a) GHRH - stimulates secretion + synthesis of GH
(b) GHIH/Somatostatin - inhibits GH release in response to GHRH + other factors
- e.g. low blood glucose stimulates GHRH, stimulating GH - GH is then monitored by GHIH
[2] Negative Feedback Loops Involving IGF-1 and GH
- high blood levels IGF-1 lead to decreased GH secretion
- suppressing somatotrophs
- stimulating release of GHIH from hypothalamus - GH also feedbacks to inhibit GHRH secretion + stimulate GHIH secretion
What are factors that influence GH secretion? [2]
[1] Diurnal Rhythm
- most of day levels are low + constant
- approx. 1 hour after onset of deep sleep, secretion increases (~5x daily values)
- then rapidly drops overly several hours
[2] Factors Superimposed on the Diurnal Fluctuations
(e. g. GH secretion increases in response to…)
(a) Exercise
(b) Stress
(c) Low Blood Glucose
(d) Increase in Blood Amino Acids after High Protein Meal
(e) Decline in Blood Fatty Acids
*side note: no known growth-related signals influence GH secretion
What are the 2 main categories of functions that the growth hormone is involved in?
[1] Metabolic Actions
[2] Growth-Promoting Actions
What are the 3 main causes of deficiencies of GH?
[1] Hypothalamic Dysfunction
- defect in the mechanisms that control GH secretion
- e.g. lack of GHRH (so GH is not stimulated to be released)
[2] Pituitary Defect
- defect in the production of GH by somatotrophs
[3] Target cells for GH Fail to Respond Normally due to Mutations in the GH Receptor
What are the symptoms of GH deficiencies dependent on?
They are dependent on age
What are symptoms/conditions that may arise if there is hyposecretion (a deficiency) of GH in children? [3]
[1] Dwarfism - LOW GROWTH HORMONE
- there is low growth hormone (GH)
- short stature (impeded skeletal growth)
- poorly developed muscles (decrease in muscle protein synthesis)
- excess subcutaneous fat (less fat mobilization)
[2] Laron Dwarfism - ABNORMAL GH RECEPTORS
- blood levels of GH are normal
- abnormal GH receptors on tissues
[3] African Pygmies - LACK OF IGF-1
- GH levels + target cell responsiveness is normal
- lack of IGF-1
What are symptoms that may arise if there is hyposecretion (a deficiency) of GH in adults?
- reduced skeletal mass + strength*
- decreased bone density
- increased risk of heart failure
What is the treatment for those with a deficiency or hyposecretion of GH?
Recombinant forms of human GH
What are the causes as to why GH may be in excess? (too much GH present)
[1] Tumour of GH-Producing Cells of Anterior Pituitary
[2] Defect in Mechanisms Regulating GH Secretion
What are the symptoms of GH excess dependent on?
They are dependent on age
What happens when there is an overproduction/hypersecretion of GH in childhood?
Gigantism
- rapid growth in height without distortion of body proportions
- hyperglycaemia (because GH conserves glucose in the blood)
What happens when there is an overproduction/hypersecretion of GH after adolescence? List the symptoms. [6]
[1] person cannot grow taller
[2] bones become thicker
[3] soft tissues proliferate (skin + connective tissue)
[4] Acromegaly - bone thickening obvious in extremities + face
- jaws and cheekbones more prominent
- hands and feet enlarge
- fingers and toes thicken
- peripheral nerve disorders often occur
[5] may develop insulin resistance and an elevated insulin level in blood
[6] may have hyperglycaemia
What is a way to measure GH excess?
Glucose Loading Test
What is the treatment for GH excess?
Somatostatin Mimetics (GHIH - Growth Hormone Inhibiting Hormone)
Who is the target audience/FDA-approved audience for Recombinant GH?
[1] GH-Deficient Children
[2] GH-Deficient Adults
[3] AIDS Patients Suffering from Muscle Wasting
[4] Shortest 1.2% of Children
Why can Recombinant GH be something that may be abused?
It is the “fountain of youth” as it can…
- reverse side-effects of aging
- promote athletic prowess
- cosmetic purposes
Extended/excessive use of GH increases the likelihood of….
(name a few)
What should be done to prevent these from occuring?
- diabetes
- kidney stones
- high blood pressure
- headaches
- joint pain
- carpal tunnel syndrome
- cancer (due to promoting uncontrolled cell proliferation)
One should reduce dosage to reduce side effects in potential uses (don’t abuse)
What type of cell is prolactin secreted by?
Lactotropes
Where organ/location does prolactin originate from and what are its functions?
Originates in specific anterior pituitary cells (lactotropes)
- it stimulates breast development + milk production
- it influences reproductive function + immune responses
What are the effects of pregnancy on prolactin secretion?
During pregnancy, prolactin secretion increases steadily
+ breast feeding maintains elevated levels of PRL secretion (8 to 12 weeks after birth)
If mother does not nurse, PRL levels decline 3 to 6 weeks after delivery
What are the two mechanisms that regulate the secretion of PRL?
[1] Two Hypothalamic Hypophysiotropic Hormones
(a) PIH/Dopamine (prolactin inhibiting hormone)
(b) PRH (prolactin releasing hormone)
[2] PRL inhibits itw own secretion via short-loop feedback
- it increases the synthesis and release of PIH
What are the biological effects of PRL before and after puberty?
It stimulates proliferation and branching of ducts in the female breast
What are the biological effects of PRL during pregnancy?
It causes the development of lobules of alveoli within which milk is produced
What are the biological effects of PRL after parturition?
It stimulates milk synthesis and secretion
What are the biological effects of PRL after reproduction?
Excess PRL blocks synthesis + release of GnRH
- prevents ovulation in women
- prevents normal sperm production in men
What are the biological effects of PRL on immunity?
- it is synthesized by maternal uterine cells during pregnancy
- suggests role in immunological balance required for acceptance of foetal tissue by mother + protection of maternal tissues from foetal invasion
What is the cause of PRL deficiency and what are the symptoms of it?
Cause: Destruction of Anterior Pituitary
Symptoms: Inability to Lactate in Women
What are the causes of PRL excess? [2]
[1] Hypothalamic Dysfunction
[2] Pituitary Tumours
Compare and contrast the symptoms of PRL excess in women, men and both sexes.
WOMEN:
- infertility
- sometimes complete loss of menses (period)
- less often lactation unassociated with pregnancy
MEN:
- decreased testosteron
- decreased sperm production
- breast development (uncommon)
- lactation (rare)
BOTH SEXES:
- decreased libido
What is the common cause of female infertility that is PRL-related?
Lactotroph Tumours
- the most common pituitary tumour
Treatment:
- removal of tumour
- administration of dopaminergic drugs to reduce PRL secretion + restore fertility
What are the 2 posterior pituitary hormones?
[1] Oxytocin (OCT)
[2] Vasopressin (Antidiuretic Hormone/ADH)
What are the functions of oxytocin?
[1] Causes milk ejection from lactation breast
- causes contraction of the cells of the alveoli of the mammary gland
- milk forced from alveoli into ducts
- evacuated by infant
[2] Causes contraction of the uterus
- used to induce labour (synthetic oxytocin given)
[3] Unclear function in men
What is oxytocin secretion controlled by? (e.g. what increases the reflex?)
Secretion is increased by reflex
- when the infant breast feeds
- within the birth canal during childbirth
What are the 2 major effects vasopressin?
[1] Enhances the Retention of Water by Kidneys
- antidiuretic effect
[2] Causes Contraction of Arteriolar Smooth Muscle
- vessel pressor effect
