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Block 1 AR > Endocrinology and cell signalling > Flashcards

Endocrinology and cell signalling Flashcards

1
Q

What is Cushsings syndrome?

A

Excess glucocorticoids - cortisol

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2
Q

Name 4 hormones which are synthesised in the Anterior Pituitary gland

A 
Growth hormone
Follicle stimulating hormone
Leutinising hormone
Thyroid stimulating hormone
Adrenocorticotrophic hormone
Prolactin
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3
Q

Give 5 functions of cortisol

A 
Maintain muscle function
Decrease bone function
Decrease connective tissue
Inhibit inflammatory and immune response
Maintain cardiac output 
Facilitate maturation of foetus
Increase glomerular filtration
Modulate emotional tone
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4
Q

List 3 things which could cause excess hormone production

A

Neoplasm in endocrine gland
Ectopic production
Hyperplasia of endocrine tissue

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5
Q

List 4 things which could cause a deficit in hormone production

A

Trauma
Disease
Autoimmune attack of gland
Under development of gland

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6
Q

Give 2 examples of peptide hormones

A

Parathyroid

ACTH

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7
Q

How are steroid hormones synthesised?

A

Hydrolysis of esters or uptake of cholesterol
Cholesterol converted to pregnenalone by C P450 in mitochondria
Pregnenalone is processed in smooth ER
Then diffuses out of the cell

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8
Q

Which cells generally have autocrine signalling as a common feature?

A

Tumour cells

Production of growth hormones perpetuates proliferation

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9
Q

What 3 effector mechanisms can be used to change cell behaviour?

A

Alter gene transcription
Alter ion balance across membrane
Alter level of enzyme activity

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10
Q

Which residues does phosphorylation mostly occur on?

A

Serine and threonine

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11
Q

In order for a molecule to diffuse across a membrane, what must occur?

A

Solute must dissolve in the hyrophobic core of the membrane

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12
Q

What are GLUT transporters?

A

Passive transporter

Glucose transported into cell and then converted to glucose 6 phosphate in order to maintain concentration gradient

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13
Q

What is an endocrine gland?

A

Gland which secretes hormones directly into the blood stream

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14
Q

What is an exocrine gland?

A

Gland which secretes chemicals via a duct

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15
Q

What tissues have endocrine function?

A

Heart
Gut
Adipocytes
Placenta

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16
Q

What are 3 types of hormones?

A

Polypeptides
Steroids
Modified amino acids

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17
Q

Describe steroid hormone synthesis

A

Hydrolysis of esters and cholesterol uptake
Conversion of cholesterol to pregnenalone in mitochondria
Processing of pregnenalone in smooth ER
Diffusion from the cell

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18
Q

Describe protein and peptide hormone synthesis

A

Gene transcription
Translation on rough ER
Post translational modification in Golgi
Packaging into secretory vesicles which are stored and ready for release when signalled

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19
Q

How is parathyroid hormone synthesised?

A

Peptide hormone
Pre-pro-PTH with signal, pro, biologically active and c terminal fragments
Cleaved twice to form active PTH

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20
Q

How is ACTH formed?

A

Peptide hormone

Formed as propriomelanocortin which is cleaved into ACTH, amino terminal fragment and B-lipotropin

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21
Q

Give an example of a tyrosine kinase receptor system

A

Insulin

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22
Q

What is the only example of a positive feedback loop in endocrinology?

A

LH surge in menstruation caused by oestrogen levels

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23
Q

Describe the anatomy of the thyroid gland

A

2 lateral lobes and an isthmus
In front of trachea
Large: 5cm long, 2-3cm deep, 3-4cm wide, 15-20g

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24
Q

What hormones does the thyroid gland make?

A

Basal metabolic rate: thyroxine (T4), tri-iodothyronine (T3)
Calcium homeostasis: calcitonin

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25
Q

What are T3 and T4 derived from?

A

Tyrosine
4 iodine molecules in T4
3 iodine molecules in T3

26
Q

Describe the thyroid gland microstructure

A

Made of follicles: follicular cells containing colloid, parafollicular cells (c cells)
Follicular cells produce T3 and T4
Parafollicular cells produce calcitonin

27
Q

What are the steps of thyroid hormone synthesis?

A

Thyroglobulin synthesis (from tyrosine) - colloid
Uptake and concentration of iodide (I-)
Oxidation of iodide to iodine (Thyroid peroxidase, luminal membrane of follicular cell)
Iodination of thyroglobulin to MIT and DIT mono-, di-iodotyrosine
Conjugation of 2 iodinated tyrosine molecules to form T4 or T3
Secretion

28
Q

What does the thyroid gland do to iodide?

A

Concentrates it

Follicles actively accumulate iodine (iodide) from blood and secrete it into colloid

29
Q

Describe iodide trapping by the thyroid gland

A

Iodide enters cell by a Na/iodide symporter located on basolateral side of follicle cell

30
Q

What are dietary sources of iodide?

A

Seawater so sea food
Sea salt
Fruit and vegetables (depends on soil/imports)
Supplemented foods (salt, chocolate)

31
Q

What is the most important nutritional deficiency? What is done to combat this in the UK?

A

Iodide

Most salt supplemented with iodine

32
Q

What regulates thryoid hormone secretion?

A

Hypothalamic, pituitary, thryoid axis
Hypothalamus releases thyroid releasing hormone
Which stimulates anterior pituitary to release thyroid stimulating hormone
This stimulates the thyroid to release T3 and T4. Release of each factor has a negative feedback effect on release of those downstream

33
Q

What is TSH (thyroid stimulating hormone)?

A

Released from anterior pituitary
Glycoprotein which stimulates follicles
Similar to FSH, LH (follicle stimulating hormone,luteinising hormone) FSH, LH and TSH: All have alpha and beta chains
Made independently

34
Q

How does TSH increase thyroid hormone synthesis and secretion?

A

Receptor -> cAMP -> activates protein kinases -> phosphorylations at multiple sites to stimulate follicles to release thyroid hormones

35
Q

Describe thyroid hormones in the circulation

A

Lipophilic so can’t readily dissolve in blood
Associated with proteins – 70% -thyroxin (thyroid) binding globulin (TBG), 30% bound to albumin
TBG has a higher affinity for T4
Only free T3/T4 can enter cell
Free hormones physiologically active

36
Q

Which thyroid hormone can activate the thyroid receptor?

A

T4 has to be converted to T3 to bind to the T3R and have effect
Deiodinases interconvert T3/T4/rT3

37
Q

Describe the types of Thyroid Hormone deiodinases

A

Peripheral tissue regulate T3 levels by increased or decreased deiodinases
Type 1 – cell surface of most cells, increase local T3
Type 2 – Intracellular raises T3 in CNS and pituitary
Type 3 - Removes iodine from T4 to make reverse T3(rT3). Especially placenta and CNS

38
Q

What type of receptor is the thyroid hormone receptor?

A

Nuclear receptor

Leads to transcription and protein synthesis

39
Q

What are the physiological actions of thyroid hormones?

A

Metabolism: all metabolic pathways, anabolic and catabolic, affects basal metabolic rate
Maturation and differentiation: bone/lungs/brain, CNS development
Neurological functions: synapse formation, myelinogenesis, neuronal outgrowth
Growth: Regulated by GH, but T3/T4 needed, skeletal

40
Q

At what point of gestation does the thyroid gland start producing thyroid hormone?

A

12 weeks

41
Q

What is Cretinism? And what test can be done for it?

A

Impaired physical and neurological development due to iodine deficiency during foetal or postnatal development
After 1st 2 years of life effects can’t be reversed screen in USA and UK
TSH in heel prick test

42
Q

What are the effects of activation of the thyroid receptor?

A

Activity of cell membrane NaKATPase, mitochondrial enzymes

Leads to increased oxygen consumption and increased metabolic rate

43
Q

In order to match increased oxygen consumption caused by T3, what needs to happen?

A 
Increase ventilation (so increase respiration) 
Deliver O2 - increase heart rate, increase blood flow, increase myocardial activity so increase cardiac output 
O2 use needs substrates for oxidation: proteins/lipids/carbohydrate metabolism so increase food intake or mobilisation of stores
44
Q

What will result from the increased metabolic rate seen with thyroid hormone receptor activation?

A 
Increased CO2, ventilation 
Increased urea 
Increased renal function 
Decreased muscle mass 
Decreased adipose tissue 
Increased thermogenesis  
Leading to sweating, increased ventilation, surface blood flow
45
Q

What symptoms might be seen in hyperthyroidism?

A

Palpatations, lose weight, increased respiration, anxiety, diarrhoea, heat tolerance, sweating, weight and muscle loss, increased appetite, nervous irritability, goitre

46
Q

What symptoms might be seen in hypothyroidism?

A

Weight gain, decreased metabolic rate, lethargic/ slow, alopecia, goitre

47
Q

What problems can be see with thyroid gland function?

A 
Gland formation/function 
Iodine supply (deficiency) 
Signalling pathways (TSH, TRH) 
Congenital or acquired 
Thyroid hormone resistance (T3R defect)
48
Q

What are the symptoms of hyperthyroidism called?

A

Thyrotoxicosis

49
Q

What is Graves’ disease?

A

Auto-antibody (TSI) binds to TSH receptor. Causes hyperthyroidism

50
Q

How can hyperthyroidism be diagnosed?

A

Measure serum TSH, free T3, free T4
Increased T3/T4
Increased TSH – fault in or above pituitary gland
Decreased TSH – thyroid gland problem (tumour/graves)

51
Q

What is an obvious sign of Graves disease?

A

Protruding eyes - exophthalmos

52
Q

What are symptoms of hypothyroidism called?

A

Myxoedema

53
Q

What can cause hypothyroidism?

A 
Hasimotos thyroiditis (auto-immune destruction)
Iodine deficiency
54
Q

How can hypothyroidism be diagnosed?

A

Measure Serum TSH, free T3, free T4
Decreased T3/T4
Increased TSH – usually

55
Q

What is goitre?

A

Enlarged thyroid gland

56
Q

What can cause goitre?

A 
Iodine deficiency (low levels of T4): induces TSH secretion 
Graves disease (high levels of T4): autoimmune disease that produces thyroid stimulating immunoglobulin - acts as TSH 
Tumours (benign or cancer)
57
Q

How do both low and high T4 induce a goitre?

A

Iodine deficiency leads to increased TSH stimulation and therefore gland growth
Graves’ disease results in thyroid stimulating immunoglobulin activating the gland and so leads to growth

58
Q

What are treatments for thyroid problems?

A

Drugs (inhibit production/replace hormone)
Radioactive iodine (131I) (destroy gland)
Surgery

59
Q

What are potential risks with thyroid surgery?

A

General surgery issues
Vocal cord nerve damage
Bleeding
Parathyroid gland damage

60
Q

List five characteristics of membrane transporters

A 
Integral membrane proteins
Channels or carriers
Specific (or selective)
Regulated
Passive or active
61
Q

What disease will someone with Hypoadrenalism suffer from?

A

Addisons

Block 1 AR (19 decks)

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