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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
What are T3 and T4 derived from?
Tyrosine 4 iodine molecules in T4 3 iodine molecules in T3
26
Describe the thyroid gland microstructure
Made of follicles: follicular cells containing colloid, parafollicular cells (c cells) Follicular cells produce T3 and T4 Parafollicular cells produce calcitonin
27
What are the steps of thyroid hormone synthesis?
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
What does the thyroid gland do to iodide?
Concentrates it | Follicles actively accumulate iodine (iodide) from blood and secrete it into colloid
29
Describe iodide trapping by the thyroid gland
Iodide enters cell by a Na/iodide symporter located on basolateral side of follicle cell
30
What are dietary sources of iodide?
Seawater so sea food Sea salt Fruit and vegetables (depends on soil/imports) Supplemented foods (salt, chocolate)
31
What is the most important nutritional deficiency? What is done to combat this in the UK?
Iodide | Most salt supplemented with iodine
32
What regulates thryoid hormone secretion?
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
What is TSH (thyroid stimulating hormone)?
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
How does TSH increase thyroid hormone synthesis and secretion?
Receptor -> cAMP -> activates protein kinases -> phosphorylations at multiple sites to stimulate follicles to release thyroid hormones
35
Describe thyroid hormones in the circulation
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
Which thyroid hormone can activate the thyroid receptor?
T4 has to be converted to T3 to bind to the T3R and have effect Deiodinases interconvert T3/T4/rT3
37
Describe the types of Thyroid Hormone deiodinases
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
What type of receptor is the thyroid hormone receptor?
Nuclear receptor | Leads to transcription and protein synthesis
39
What are the physiological actions of thyroid hormones?
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
At what point of gestation does the thyroid gland start producing thyroid hormone?
12 weeks
41
What is Cretinism? And what test can be done for it?
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
What are the effects of activation of the thyroid receptor?
Activity of cell membrane NaKATPase, mitochondrial enzymes | Leads to increased oxygen consumption and increased metabolic rate
43
In order to match increased oxygen consumption caused by T3, what needs to happen?
``` 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
What will result from the increased metabolic rate seen with thyroid hormone receptor activation?
``` 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
What symptoms might be seen in hyperthyroidism?
Palpatations, lose weight, increased respiration, anxiety, diarrhoea, heat tolerance, sweating, weight and muscle loss, increased appetite, nervous irritability, goitre
46
What symptoms might be seen in hypothyroidism?
Weight gain, decreased metabolic rate, lethargic/ slow, alopecia, goitre
47
What problems can be see with thyroid gland function?
``` Gland formation/function Iodine supply (deficiency) Signalling pathways (TSH, TRH) Congenital or acquired Thyroid hormone resistance (T3R defect) ```
48
What are the symptoms of hyperthyroidism called?
Thyrotoxicosis
49
What is Graves' disease?
Auto-antibody (TSI) binds to TSH receptor. Causes hyperthyroidism
50
How can hyperthyroidism be diagnosed?
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
What is an obvious sign of Graves disease?
Protruding eyes - exophthalmos
52
What are symptoms of hypothyroidism called?
Myxoedema
53
What can cause hypothyroidism?
``` Hasimotos thyroiditis (auto-immune destruction) Iodine deficiency ```
54
How can hypothyroidism be diagnosed?
Measure Serum TSH, free T3, free T4 Decreased T3/T4 Increased TSH – usually
55
What is goitre?
Enlarged thyroid gland
56
What can cause goitre?
``` 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
How do both low and high T4 induce a goitre?
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
What are treatments for thyroid problems?
Drugs (inhibit production/replace hormone) Radioactive iodine (131I) (destroy gland) Surgery
59
What are potential risks with thyroid surgery?
General surgery issues Vocal cord nerve damage Bleeding Parathyroid gland damage
60
List five characteristics of membrane transporters
``` Integral membrane proteins Channels or carriers Specific (or selective) Regulated Passive or active ```
61
What disease will someone with Hypoadrenalism suffer from?
Addisons

Block 1 AR (19 decks)

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