Endocrinology

Question 1

What are the characteristics of the hormone super families?

Answer 1

Peptides- stored for a day, secreted via exocytosis, lasts for mins-hours, works for mins-hours
Steroids- stored for mins-hours, secreted by diffusion, lasts for hours, works for hours-day
Thyroid hormones- stored for weeks, secreted by proteolysis, last for days, work for a day
Catecholamines- stored for a day, secreted by exocytosis, last for sec-mins, work for seconds

Question 2

Describe peptide hormones

Answer 2

Water soluble
Largest in number
Normally proteolytic ally cleaved to form the active hormone
Stored in vesicles- for immediate release
Made as preprohormones with a signal peptide and ‘inactive’ fragment

Question 3

Describe amino acid derivatives as hormones

Answer 3

Thyroid hormones from tyrosine in the thyroid gland

Question 4

Describe steroid hormones

Answer 4

Lipophilic- easily pass through the plasma membrane
Includes sex hormones, glucocorticoids, thyroid hormone and vitamin D
Not stored- produced on demand
Produced in adrenal cortex, corpus luteum and ovaries in women and testes in men
Starts from cholesterol (transported into mitochondria by StAR)➡️ pregnenolone by P450cc through 2 hydroxylase and one cleavage reaction

Question 5

List the endocrine glands

Answer 5

Hypothalamus
Pituitary
Thyroid
Parathyroid a
Adrenals
Pancreas
Ovary
Testes 
(Heart, intestines, skin, liver, kidney)

Question 6

What is a hormone receptor?

Answer 6

Bind the hormone specifically
Be able to detect it and high enough affinity in blood amount related molecules
The receptor must be only in specific tissues?
Must be saturable
Reversible
Must mediate some biological response

Question 7

Describe intrinsic tyrosine kinase activity

Answer 7

An enzyme that has the intrinsic ability to transfer a phosphate group to a tyrosine residue
Eg. Epidermal growth factor (EGF) receptor 1-4, ligand induced dimerisation, signal transduction processes-
Eg. Dimerization➡ transphosphorylation➡ GRB➡ SOS➡ Ras(+GTP)
Insulin receptor- PI 3-kinase

Question 8

Describe recruited tyrosine kinase activity

Answer 8

JAK-STAT
Ligand binds (cytokines) JAK recruited to pohosphorylatr the receptor which then recruits STAT
STAT is phosphorylate - now active and localises to the nucleus to affect transcription

Question 9

Describe the G protein coupled receptor

Answer 9

7-pass transmembrane protein
Act via an intracellular second messenger system eg. cAMP, inositol, IP3, diacylglycerol (DAG)
The G proteins are heterotrimeric- alpha, beta and gamma subunits
Activation of a receptor causes a confirmation change in the alpha subunit allowing ADP exchange for ATP releasing the alpha unit and the beta-gamma complex forms a functional unit
These act as second messengers eg. DAG activates PLC➡ Ca➡ calmodulin➡ calmodulin-activated kinases
And PKC
Results in phosphorylated target proteins

Question 10

Describe steroid hormone receptors

Answer 10

Few with cell surface receptors
Most receptors are in the cytoplasm and as a complex binds to a gene target
Type 1 receptors- work as homodimers eg. Glucocortoid, mineralcorticoid, progesterone, oestrogen and androgen
Active transport to nucleus AMD bind to sequence es of DNA called hormone response elements (HREs)
Type 2 receptors- heterodimerise with RXR eg. VDR, RAR, TR
Retained in nucleus
When not ligand bound in complexes with co-repressor proteins, ligand binding recruits co-activator proteins

Question 11

Described the structure of nuclear receptors

Answer 11

Conserved
AF1 at the N terminal, DNA binding in the middle and AF2 near the C terminal
AF1+2 work synergistically for transcriptional activation

Question 12

Describe HRE

Answer 12

Hormone response elements
Monomeric- A/T rich region 5' to half-site
Dimeric- Pal HRE- palindrome or inverted
DR HRE- direct repeat
IP HRE- inverted palindrome
Recognised by P-box on zinc fingers

Question 13

Describe the orgnaisation of the hypothalamus

Answer 13

A collection of brain nuclei or centres which have impoortnat control and integrative functions
Important for homeostasis and primitive functions
Controls autonomic functions via brainstem autonomic centres
Controls endocrine function via the pituitary gland

Question 14

List some hypothalamic hormones

Answer 14

Thyroid releasing hormone- TRH
Gonadotrophin Releasing hormone- GnRH
Growth hormone releasing hormone- GHRH
Somatostatin
Corticotropin releasing hormone- CRH
Dopamine
Small peptides
Release is pulsatile inducting rapid effects on the release of cognate anterior pituitary hormone

Question 15

Describe the pituitary gland

Answer 15

Anterior pituitary hormones regulated by secreted hypothalamic factors
Posterior pituitary hormones synthesised in hypothalamus and transported via neural projections
Structurally continuous with the hypothalamus by the pituitary stalk

Question 16

List the anterior pituitary cell types and the hormone they secrete hormones

Answer 16

Thyrotroph- thyroid stimulating hormone (TSH)
Corticotroph- adrenocorticotrophic hormone (ACTH)
Gonadotroph- luteinizing hormone and follicle stimulating hormone (LH/FSH)
Somatotroph- growth hormone (GH)
Lactotroph- prolactin (PRL)
Single chain hormones- PRL, GH
Two chain glycoproteims: common alpha + unique beta- TSH, LH, FSH

Question 17

List the posterior pituitary hormones

Answer 17

ADH
Neurophysins
Oxytocin

Question 18

What is POMC?

Answer 18

A large precursor polypeptide that is ther source of several important biologically active substances including:
ACTH
Gamma-MSH
Beta-LPH (corticotroph cell)➡ gamma-LPH+ beta-endorphin (brain)

Question 19

What are the different types of secretion?

Answer 19

Constitutive
Regulated
Pulsatile
Diurinal

Question 20

Describe thyroid stimulating hormone

Answer 20

TSH is made in thyrotrophs in the anterior pituitary is response to pulsatile TRH release in the hypothalamus
Pituitary failure can result in secondary hypothyroidism
Pituitary tumour can result in secondary hyperthyroidism

Question 21

Describe gonadotrophins

Answer 21

LH and FSH
Made by gonadotrophs (most mame both, some only make one) in the anterior pituitary on response to GnRH
Regulate testosterone biosynthesis and spermatogenesis in the testes
Regulate menstruation and fertility in the ovary
Both act through cell membrane receptors coupled to Gs proteins➡ cAMP➡ PKA

Question 22

Describe adrenocorticotropic hormone

Answer 22

ACTH Synthesised by corticotrophs in the anterior pituitary
Stimulates GPCR coupled to cAMP
stimulates enzymes that convert cholesterol to cortisol or sex steroid hormones (eg StAR)

Question 23

Describe prolactin

Answer 23

Made in lactotrophs- production increases during pregnancy due to increase in oestrogen
Inhibits its own release
Stimulates mammary gland development via DNA synthesis, epithelial cell proliferation, synthesis of lactose, casein, lactalbumin, free fatty acids
Maintains lactation via synergy with glucocorticoids, inhibited by oestrogen and progesterone

Question 24

What is a prolactinoma?

Answer 24

Most common pituitary tumour
Interfere with HPG axis resulting in infertility, amenorrhoea, galactorrhoea
Treatment with dopamine agonists

Question 25

Describe growth hormone

Answer 25

Released by somatotrophs
Pulsatile secretion
Stimulated by low glucose, exercise and sleep
Protein hormone carried by proteins
Release inhibited by somatostatin
Deficiency or resistance:
GH receptor mutations- laron syndrome dwarfism- treated with IGF1
GH deficiency- treated with recombinant hGH

Question 26

Describe ADH

Answer 26

Nonapeptide suyntheised by the posterior pituitary
Packaged with the carrier protein neurophysin in secondary granules in the magnocellular neurones of the periventricular and supraptic nuclei
Acts in collecting ducts in the kidneys- aquaporins
Diabetes insipidus- posterior pituitary damage may reduce ADH and urine cannot be concentrated

Question 27

Describe oxytocin

Answer 27

Synthesised in the posterior pituitary
Stimulates contraction of smooth muscle of the breast and uterus
Can be given to induce labour
Neuro-endocrine reflexes