Lecture 11 - Pituitary Gland

Question 1

What is the relationship btw the hypothalamus and the pituitary gland?

Answer 1

• Complex functional unit

- Major link btw the endocrine and nervous system

Question 2

Where is the pituitary gland?

Answer 2

• Beneath the hypothalamus

- In a socket of bone called sella turcica

Question 3

Give some examples of processes that are modulated by the hypothalamus & the pituitary gland

Answer 3

• Thyroid gland function
• Lactation
• Adrenal gland function
• Water homeostasis
• Body growth

Question 4

What is the distinct embryological origin of the anterior pituitary gland (adenohypophysis) ?

Answer 4

• Primitive gut tissue

- Oral ectoderm

Question 5

What is the distinct embryological origin of the posterior pituitary gland (neurohypophysis) ?

Answer 5

• Comes from neuroectoderm

- Primitive brain tissue

Question 6

Which pituitary gland is connected to the hypothalamus?

Answer 6

• Posterior pituitary gland

- Hypo. drops down through the infundibulum

Question 7

What is the definition of a nuclei?

Answer 7

• A collection of cell bodies w. similar func.

Question 8

Where is oxytocin & ADH (vasopressin) formed & stored?

Answer 8

• Produced by neurosecretory cells in the supraoptic & paraventricular nuclei of hypothalamus
• Stored & released from P.P to act on distant targets

Question 9

How does the hypothalamus control the function of the anterior pituitary gland?

Answer 9

• Hypothalamus synthesise hormones –> stored in median eminence before release into hypophyseal portal system
• The hormones stimulate/inhibit target endocrine cells in A.P
• Hormones in A.P act on distant targets (endocrine function) or act on neighboring cells (autocrine & paracrine func.)

Question 10

What is oxytocin responsible for?

Answer 10

• Ferguson’s reflex

- Milk let down and uterine contractions during birth

Question 11

Name all 6 tropic hormones of the hypothalamus

All hormone have direct effect on release on A.P hormones

Answer 11

• TRH (Thyrotropin RH)
  Stimulate A.P to secrete TSH
• CRH (Corticotropin RH)
  Stimulate A.P. to secrete ACTH
• PIH (Prolactin release inhibiting hormone)
  Prevent prolactin secretion
• GnRH (Gonadotropin RH)
  Stimulate FSH & LH
• GHRH (Growth hormone RH/ somatotropin)
• GHIH (Growth hormone IH/ somatostatin)

Question 12

What is the hormones produced in A.P?

Answer 12

• TSH (Thyroid stimulating H)
  Secretion of T3 & T4
• ACTH (Adrenocorticotropic H)
  Secretion of cortisol from adrenal glands
• LH + FSH
  Stimulate ovulation + development of follicles/sperm
• PRL
  Milk secretion & mammary gland formation
• GH
  Growth & energy metabolism + IGF (Insulin-like growth factor/Somatomedin: stimulate growth and decrease B.G)

Question 13

Name factors that influence growth

Answer 13

• Genetics
• Nutrition
• Enviroment
• Hormones

Question 14

What is the diff. btw necrosis and apoptosis?

Answer 14

• Necrosis is cell death by damage. (caused by hypoxia, lack of nutrients, cellular damage)
• Apoptosis is programmed cell death

Question 15

What is GH? What is it stimulated & inhibited by?

Answer 15

• Protein hormone that has a signal peptide that must be cleaved before proper folding
• ✅ by GHRH, X by somatostatin
• ✅ deep sleep, X REM
• ✅ stress, exercise, ⬇️ F.A. & glucose
• ✅ fasting, X obesity

Question 16

What does liver & skeletal muscle produce in response to GH?

Answer 16

• IGF (Insulin-like growth factors)

Question 17

What is the function of GH & IGF?

Answer 17

• Stimulates long bone growth
  (length + width before epiphyseal plate closure, width after)
• IGF stimulate bone and cartilage growth

Both:

• Maintain muscle & bone mass
• Promote healing and tissue repair
• Modulating metabolism

Question 18

List factors that control GH secretion

Answer 18

• ✅ deep sleep, ❌ REM
• ✅ stress (trauma, surgery, fever) , exercise
• ✅ decrease glucose/fatty acids
  N.B. GH stimulates gluconeogenesis, lipolysis
• ✅ fasting, ❌ obesity

Question 19

How does long loop and short loop feedback regulate GH secretion?

Answer 19

• IGFs inhibit GH by stimulating the release of somatostatin

- Short loop mediated by GH itself via somatostatin release

Question 20

What does GH deficiency lead to in childhood? What is the treatment?

Answer 20

• Pituitary dwarfism: proportionate type of dwarfism
• Complete or partial deficiency
• Result in delayed or X sexual development n teen years, slow growth rate, short stature
• Treatment: GH therapy

Question 21

What does GH excess result in childhood?

Answer 21

• Gigantism: Epiphyseal plates X close, long bones grow

- Rare (often caused by pituitary adenoma)

Question 22

What does GH excess result in adults?

Answer 22

• Acromegaly: occurs after epiphyseal plates close, long bones X grow
• Large extremities: hands,feet,lower jaw

Question 23

How does GH exert its effects on cells?

Answer 23

• GH receptors activate Janus kinases (JAKs)
• = know
• 1. GH binds to receptor –> receptor dimerisation
     
     2. Receptor change confirmation
     3. Activates kinase activity of receptor
     4. Phosphorylated tyrosine residues become binding sites for other signaling proteins
• 5. Activation of signaling proteins
• 6. Transcription factors activated and IGFs produced

Question 24

What type of IGFs are there?

Answer 24

• IGF 1 = adults, IGF 2 = kids

- Binding proteins modulate availability of IGFs

Question 25

What does IGF do?

Answer 25

- Increase protein synthesis - Stimulate hyperplasia, hypertrophy - Increase lipolysis

Question 26

How do pituitary tumours present?

Answer 26

- Mass effect of tumour on local structures: vision loss, headache - Abnormality in pituitary function: Hypo-/Hyper-

Question 27

What causes prolactinoma? How is it treated?

Answer 27

- Pregnancy, Stress, Exercise - Treated with tablets not operation (even if tumour is very large) - Tumour shrink with dopamine agonist (inhibits prolactin) **X give dopamine antagonists (anti-sickness/anti-psychotic drugs) = can cause high prolactin

Question 28

What are long-term complications of untreated acromegaly?

Answer 28

- Premature cardiovascular death - Increased risk of colonic tumours - Hypertension and diabetes - Disfiguring of body

Question 29

What are some tests to confirm acromegaly?

Answer 29

- Oral Glucose Tolerance Test with GH response (Failure to suppress confirms diagnosis) - Elevated IGFs - Growth Hormone Day Curve (elevated GH)

Question 30

What are some other treatment for excess GH (acromegaly)?

Answer 30

1. Reduce GH secretion: (i) Dopamine agonist (cabergoline) (ii) Somatostatin analogues (SSA) 2. Block GH receptor 3. Radiotherapy: External beam (short bursts multiple times to remove tumour) or Gamma knife (High conc. once)

Question 31

A 63 year old man who has been suffering from polydipsia and polyuria for the past 12 months is diagnosed with neurogenic diabetes insipidus (central diabetes insipidus). What would be a clinical consequence of this disease if left untreated?

Answer 31

- Hypernatraemia - caused by lack of ADH (vasopressin). This results in the production of polyuria - Manifestations of hypernatraemia include confusion, neuromuscular excitability, hyperreflexia, seizures, and coma

Question 32

``` Luteinizing hormone (LH) is produced by the anterior pituitary gland and in females plays an important role in triggering ovulation (LH surge) and in the development of the corpus luteum. What is the role of this hormone in men? ```

Answer 32

Control of the production of testosterone by the testis

Question 33

A surgeon operates on a 56 year old woman to remove a pituitary adenoma. He gains access to the adenoma by inserting an endoscope and his surgical instruments through her nose. Which surgical procedure was used by this surgeon?

Answer 33

- Transsphenoidal surgery - access to the pituitary gland is gained by inserting instruments through the nose and sphenoid bone into the sphenoidal sinus cavity.

Question 34

What is the range of macro- & micro- tumour size?

Answer 34

- Macro-adenoma= > 1cm | - Micro-adenoma = < 1cm

Question 35

What are some examples of dopamine agonists?

Answer 35

- bromocriptine and cabergoline | very effective in reducing size of tumour

Question 36

Symptoms and signs of acromegaly

Answer 36

- Broad nose, coarse facial features, thick lips and a prominent supraorbital ridge (the crest of bone situated on the frontal bone of the skull) - Enlargement of the hands and feet - skin is often greasy with excessive sweating. - Deepening of the voice also occurs due to hypertrophy of the soft tissues of the upper airways.

Question 37

Why can't acromegaly be diagnosed simply by measuring plasma GH and how should it be diagnosed?

Answer 37

- GH varies a lot during the day - IGF-1 would be measured (varies less) + oral glucose tolerance test - In a normal person, a high blood glucose would inhibit GH production by the anterior pituitary. - in an oral glucose tolerance test you purposely raise blood glucose and determine the plasma GH level. (The patient drinks 75 g of glucose solution and over 2 hours plasma glucose and GH are monitored. If GH doesn't drop to below 1 ng/mL, diagnosis cfm)

Question 38

State mechanism of direct and indirect effects of GH on target cells.

Answer 38

- Direct: Binds to growth hormone receptor on target --> intracellular signaling cascades --> ⬆️ growth and cellular metabolism - Indirect: GH stimulate liver + skeletal muscles to secrete IGFs --> ⬆️ growth and cellular metabolism