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Semester 2 - MEH > 15. The HPA axis & Growth hormone > Flashcards

15. The HPA axis & Growth hormone Flashcards

1
Q

What is the hypothalamic pituitary axis?

A

The hypothalamus and pituitary gland form a complex functional unit that serves as the major link between the endocrine and nervous systems

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2
Q

Which processes do the hypothalamus and pituitary modulate?

A
  • Body growth
  • Milk secretion
  • Reproduction
  • Adrenal gland function
  • Water homeostasis
  • Lactation
  • Thyroid gland function
  • Puberty
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3
Q

Where is the pituitary gland?

A

The pituitary gland sits beneath the hypothalamus in a socket of bone called the sella turcica at the base of the
skull

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4
Q

What does the pituitary gland consist of and what is it origin?

A

•Anterior pituitary gland (adenophypophysis)
- arises from the evagination of the oral ectoderm (Rathke’s pouch) (primative gut tissue)

•Posterior pituitary (neurohypophysis)
- orginates form the neruoexctoderm(primitive brain tissue)

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5
Q

What is the connection between the hypothalamus and posterior pituitary gland?

A

The posterior pituitary gland is physically connected to the hypothalamus, since the hypothalamus
drops down through the infundibulum to form the posterior pituitary

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6
Q

Are the anterior and posterior pituitary glands similar?

A

The anterior and posterior pituitary glands have distinct embryological origins and distinct functions

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7
Q

Why is the posterior pituitary gland not a real gland?

A

Although it is sometime referred to as the posterior pituitary “gland”, the posterior pituitary is actually not a gland at all since it does not synthesise any hormones, just release them

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8
Q

What is the function of the posterior pituitary?

A
  • Oxytocin and antidiuretic hormone produced by neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus.
  • Transported down nerve cell axons to the posterior pituitary.
  • Stored and released from posterior pituitary into the general circulation to act on distant targets
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9
Q

What is the function of the anterior pituitary?

A

• Hormones synthesised in hypothalamus are transported down axons and stored in median eminence before release into hypophyseal portal system.
• These hormones stimulate (or inhibit) target endocrine cells in the anterior pituitary gland (neurocrine
function).
• Endocrine cells of anterior pituitary secrete a variety of hormones into the bloodstream to act on distant target
cells (i.e. endocrine function).
• Anterior pituitary hormones also effect neighbouring cells (autocrine and paracrine function).

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10
Q

How do the hormones produced by nerve cells in the hypothalamus act via two distinct neurocrine pathways?

A
  • Direct effects on distant target tissues via oxytocin and antidiuretic hormone from the posterior pituitary
  • Hormones secreted exclusively into hypophyseal portal system affect endocrine cells within the anterior pituitary
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11
Q

What is the function of Oxytocin?

A

• The stimulus of suckling in the milk let-down reflex is transmitted via neurons from the breast to the hypothalamus resulting in release of oxytocin from the posterior pituitary.
• Once in the bloodstream, oxytocin travels to the mammary glands and causes milk release by activating oxytocin receptors on the myoepithelial cells surrounding the mammary alveoli causing them to contract squeezing milk into the duct system.
• During childbirth the stimulus of pressure on the cervix
and uterine wall is again transmitted to the hypothalamus via neuronal input and the release of oxytocin from the posterior pituitary into the general circulation initiates powerful uterine contractions by activation of oxytocin receptors on uterine smooth muscle cells.

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12
Q

What is the function of Antidiuretic hormone (vasopressin)?

A

• ADH causes a reduction in urine production.
• Receptors for ADH are present on the collecting ducts in the kidneys and when activated by ADH facilitate an increase in permeability by inducing translocation of aquaporin water channels in the plasma membrane of
the collecting duct cells allowing more reabsorption of water back into the blood.
• Osmoreceptors in the hypothalamus detect changes in plasma osmolality and control the amount of ADH released and also the feeling of thirst.
• ADH also increase peripheral vascular resistance by activating ADH receptors on the smooth muscle cells of blood vessels causing vasoconstriction and an increase in arterial blood pressure.

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13
Q

How does alcohol excess cause dehydration?

A

Drinking alcohol inhibits ADH release from the posterior pituitary explaining the increased urination and ultimately dehydration.

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14
Q

Why is Vasoconstriction mediated by ADH important?

A

Vasoconstriction mediated by ADH is particularly important for restoring blood pressure in hypovolemic shock during haemorrhage

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15
Q

When is synthetic oxytocin given?

A

ynthetic oxytocin (Pitocin) is often administered to increase uterine tone and control bleeding just after birth

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16
Q

What are the 6 tropic hormones produced in the hypothalamus?

A

• TRH - Thyrotropin releasing hormone
• (PRH) - Prolactin releasing hormone(no evidence that this exists) = TRH (minor +ve control on prolactin)
• PIH - Prolactin release-inhibiting hormone (Dopamine)
• CRH - Corticotropin releasing hormone
• GnRH - Gonadotropin releasing hormone
• GHRH - Growth hormone releasing hormone
• GHIH - Growth hormone-inhibiting hormone (Somatostatin)
(RH= releasing hormone, IH = inhibitory hormone)

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17
Q

What does tropic hormone mean?

A

Tropic hormones affect the release of other hormones in the target tissue
NOTE: Do not confuse with trophic. (Trophic hormones affect growth)

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18
Q

What are the 6 hormones produced by the anterior pituitary

A

• TSH - Thyroid stimulating hormone
Secretion of thyroid hormone from thyroid gland
• ACTH - Adrenocorticotropic hormone
Secretion of hormones from adrenal cortex
• LH - Luteinising hormone
Ovulation and secretion of sex hormones
• FSH - Follicle stimulating hormone
Development of eggs and sperm
• PRL - Prolactin
Mammary gland development and milk secretion
• GH - Growth hormone
Growth and energy metabolism. Stimulates IGFs

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19
Q

For each of the 6 hormones produced by anterioir pituitary gland, list the:

  • Anterior pituitary cell type
  • Hypothalamic Stimulating hormone
  • Hypothalamic Inhibitory hormone
  • Main action of anterior pituitary hormone once released into general circulation
A 
• Thyrotrope --> TRH --> TSH --> thyroid gland --> thyroid hormone(T3 + T4) --> metabolic rate 
• 
• 
• 
• 
•
20
Q

Explain the different types of negative feedback in the hypothalamic-pituitary-adrenal axis

A
  • The hypothalamus will increase CRH when under stress, low bp, hypoglycaemia or fever
  • Anterior pituitary can decrease the CRH release from the hypothalamus through a short loop feedback
  • Cortisol levels can act on the anterior pit to stop ACTH release in another short loop feedback or they can act on the hypothalamus to stop CRH release in long loop feedback
21
Q

Describe how the secretion of hypothalamic releasing hormones, anterior pituitary hormones and peripheral effector hormones are regulated by negative feedback loops

A

• In ultrashort loop negative feedback the hypothalamic releasing factor itself (hormone 1) limits its own production in an autocrine/paracrine fashion within the
hypothalamus.
• Further short-loop negative feedback comes either from inhibition of hypothalamic releasing hormone production or stimulation of hypothalamic inhibiting hormone production mediated by the anterior pituitary hormone (hormone 2) released in response to the hypothalamic releasing hormone.
• The final peripheral effector hormone in the pathway (hormone 3) also acts back on the hypothalamic pituitary axis in negative feedback loops that inhibit production of the respective anterior pituitary hormone via direct long loop negative feedback and the respective hypothalamic releasing factor via indirect long loop negative feedback.

22
Q

What is growth influenced by?

A
  • Nutrition
  • Genetics
  • Environment
  • Hormones
23
Q

Where is growth hormone produced?

A

Produced in the anterior pituitary

24
Q

What stimulates and inhibits growth hormone production?

A
  • Stimulated by hypothalamic GHRH

* Inhibited by hypothalamic Somatostatin

25
Q

Describe growth hormone structure

A

•Protein hormone (191 aa) has signal peptide that must be cleaved before proper folding

26
Q

How do cell of liver and skeletal muscle respond to growth hormone?

A
  • Growth-promoting effects mainly exerted indirectly via insulin-like growth factors (Somatomedins)
  • In response to GH, cells of the Liver and Skeletal muscle produce and secrete IGFs which are hormones that act to stimulate body growth and regulate metabolism.
27
Q

What do GH and IGFs do?

A

• GH stimulates long bone growth
- Length & width prior to epiphyseal closure
- Width after epiphyseal closure
• IGFs stimulate both bone and cartilage growth

28
Q

What do GH and IGFs do in adults?

A

GH and IGFs help maintain muscle and bone mass and promote healing and tissue repair as well as modulating metabolism and body composition.

29
Q

What acts as the principal control point of GH secretion and how?

A

Principal control is via the hypothalamus
•GHRH (↑ GH secretion)
•Somatostatin (↓ GH secretion)

30
Q

How is GH secretion regulated metabolically?

A

Secretion is regulated metabolically by plasma glucose and free fatty acid concentrations:
• ↓ in glucose or fatty acids leads to ↑ in GH secretion
• ↑ in glucose or free fatty acid leads to ↓ in GH secretion
• Fasting ↑ GH secretion, Obesity ↓ GH secretion

31
Q

How does the CNS regulate GH secretion?

A

The CNS regulates GH secretion via inputs into the hypothalamus effecting GHRH and somatostatin levels:
• There is a surge in GH secretion after onset of deep sleep
• Light sleep (Rapid Eye Movement (REM) sleep) inhibits GH secretion
• Stress (e.g. trauma, surgery fever) increases GH secretion
• Exercise increases GH secretion

32
Q

Which hormone has shown to also affect GH secretion?

A

The hormone ghrelin has also been shown to increases the production of growth hormone.

33
Q

Describe how regulation of GH secretion occurs via LONG LOOP negative feedback mechanisms

A

LONG LOOP negative feedback (both direct and indirect) is mediated by IGFs which:
• Inhibit the release of GHRH from the hypothalamus.
• Stimulate the release of somatostatin from the hypothalamus.
• Inhibit the release of GHRH from the anterior pituitary.

34
Q

Describe how regulation of GH secretion occurs via SHORT LOOP negative feedback mechanisms

A

SHORT LOOP negative feedback is mediated by GH itself via the stimulation of somatostatin release from the hypothalamus

35
Q

How does GH exert its effects on cells?

A
  • GH acts on cells both directly through its own receptor and indirectly through the induced production of Insulin-like Growth Factor-I (IGF-I).
  • Only those cells expressing GH receptors(tyrosine kinase receptor) can respond to GH.
  • GH receptors are coupled to an intracellular enzyme called Janus kinase (JAK). When the receptors are activated, they dimerise and change conformation which activate janus kinase which autophosphorylates itself. The phosphorylated janus kinase act as binding sites for other signalling pathways. This results in signalling pathways that activate transcription factors to increase production of IGFs.
  • One of the direct effects of GH in adipose tissue is to increase the rate of lipolysis (a catabolic effect).
  • GH also has direct effects on increasing the rate of protein synthesis (an anabolic effect).
36
Q

Decribe IGFs

A

• 2 IGFs in mammals (IGF1 and IGF2)
- IGF2 mainly involved in fetal growth
- IGF1 major growth factor in adults.
• Actions of IGFs can be paracrine and autocrine as well as endocrine
• IGFs act through IGF receptors (distinct from GH receptors) to modulate:
- Cell growth (Hypertrophy)
- Cell number (Hyperplasia)
- Increase in the rate of protein synthesis
- Increase in the rate of lipolysis in adipose tissue
• In some tissues, IGF-1 inhibits apoptosis and some types of tumour express abundant IGF-I receptors which inhibit apoptosis.

37
Q

What are Other hormones also influence growth?

A

• Insulin - Enhances somatic growth; interacts with IGF
receptors
• Thyroid hormones - Promote CNS development and enhance GH secretion
• Androgens - Accelerate pubertal growth spurt; increase muscle mass; promote closure of epiphyseal plates
• Estrogens - Decrease somatic growth; promote closure of epiphyseal plates
• Glucocorticoids - Inhibit somatic growth

38
Q

In which tissues are IGFs produced?

A

Mainly produced in the liver (~75%) and skeletal muscle

- although many other tissues such bone, kidney and the central nervous system

39
Q

How are IGFs transported in the blood and what is the implication of this?

A

Circulate in the blood bound to specific binding proteins

- modulate their availability to activate IGF receptors on target cells

40
Q

What class of receptors does the IGF receptor belong to?

A

Tyrosine kinase

41
Q

What effect does IGF-2 binding to its receptor have in adults?

A
  • It does not dimerise

- No tyrosine kinase activity (targets IGF2 for lysosomal degradation)

42
Q

What receptors can IGF-1 bind to?

A
  • IGF-1 receptor
  • Hybrid receptor (of IGF-1 and insulin receptors)
  • insulin receptors (at much higher concentrations)
43
Q

What does GH deficiency in childhood cause?

A

Results in pituitary dwarfism:
• Proportionate type of dwarfism
• Complete or Partial deficiency
• Both types respond to GH therapy
• Height below 3rd percentile on standard growth charts
• Growth rate slower than expected for age
• Delayed or no sexual development during teen years

44
Q

What does excess GH in childhood result in?

A

Gigantism:

• Rare (~ 3 cases per 106 people)

45
Q

What is excess GH often caused by?

A

Pituitary adenoma

46
Q

What does excess GH in adulthood result in?

A

Acromegaly: Literally means large extremities:
•Hands
•Feet
•Lower Jaw

Semester 2 - MEH (23 decks)

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