Introduction to endocrinology

Question 1

Define hormone

Answer 1

A hormone (from Greek ‘ormao’ – to arouse or excite) is a chemical released by a cell in one part of the body that sends out messages that affect cells in other parts of the body
- **as opposed to paracrine molecules or molecules with ‘next door effect’

Question 2

List the three types of hormones with examples

Answer 2

• peptides/proteins e.g insulin
• amines e.g. catecholamines
• steroids e.g. thyroxine

Question 3

What are the factors that can modify hormone actions?

Answer 3

• Hormone actions can be modified by;
  – Changing levels in plasma (e.g more clearance = less hormone)
  – Changes in binding proteins (more binding = less availability )
  – Changes in receptor populations (more or less receptors= more or less effect)
  – Changes in post-receptor signalling cascades (halted cascade in T2DM)

Question 4

Describe the effect of negative feedback on hypothalamus and pituitary secretion

Answer 4

• hypothalamus releases releasing hormones eg TRH, CRH, GnRH- ‘tropins’
• These stimulate the release of hormones from the anterior pituitary e.g. Tsh, FSH, LH and ACTH
• These stimulating hormones circulate to endocrine organs to produce the rlevant hormoen: thyroid hormones, glucocorticoids, inhibin/oestrogen/progestins/androgens
• These hormones then exert their effects on the target cells
• Homeostatic mechanisms control levels of homrone: elecated lecels of hormones prodced by the endocrine organ send negative signals to potuitary gland and hypothalmus to stop release
  - elevated thyroxine inhibits TRH and TSH so that the thyroid gland is less stimulated

Question 5

List the releasing hormones, their corresponding pituitary hormones, endocrine target organs and second hormones

Answer 5

• TRH -> TSH -> thyroid gland -> thyroid hormones (T3/4)
• CRH -> ACTH -> adrenal cortex -> glucocorticoids
• GnRH-> FSH -> testes and inhibin, ovaries and inhibin and estrogens
• GnRH -> LH -> ovaries and progestinss and estrogens, testes and androgens

Question 6

Describe the features of the insulin receptor family

Answer 6

Note the common features of TM proteins of the insulin receptor family:
- EC domain binds hormone—more diverse among members
- Signal is based through membrane to IC tyrosine kinase domains
- IC domain more conserved across members
- Tyrosine kinase domain activates signalling cascade

Note 2: insulin EC domain consists of dimer connected with disulphide bond

Question 7

Describe the key features of the insulin receptor signalling cascade

Answer 7

Key notes about insulin receptor signalling cascade:
- insulin binds Ec domain of receptor
- Instigates a conformational change
- IC domain subunits are drawn closwr together
- Tyrosine kinase omitiates phosphorylation cascade
- IRS1 activated
- Activates PI3k
- Converts PIP2 to PIP3
- Stimulates AKT
- inhibits GNG in liver
- Increases GLUT4 expression and glucose uprake
- Activates glycogen synthase

Question 8

Describe the key features of the menstrual cycle

Answer 8

Key notes aboyt the menstrual cycle:

• consists of two main phases: follicular and luteal
• follicular:
  -FSH and LH rises
  
  • stimulates oestrogen which dominates
  • Oestrogen stimulates follicle and lining development
  • Terminates at ovulation where FH and LH peak due to positive feedback (from?)
• Luteal:
  
  • progesterone dominates, maintains lining
  • Temperature rises
  • Corpus luteum degenerates
  • As progesterone falls, lining breaks down

Cycle can be manipulated with contraceptives

Question 9

Describe an example of how hormones can affect a foetus

Answer 9

Notes on the connection between mother and fetus:
- CRH can cross into the placenta
- this results in the production of cortisol in the foetus
- enhancing lung maturation
- also enhancing secretion of surfactant, resulting in inflammation at the amnion, contributing to contractions and eventually labour
- CRH concentration and delivery is increased just before birth

Question 10

Describe the uses of ultrasound

Answer 10

uses of ultrasound:
- to measure the size of the foetus and get an approximate age of embryo/length of the pregnancy
- count the heads
- observe flow in umbilical artery via Doppler — pre-eclampsia impacts continuous flow

Question 11

Describe the control of lactation

Answer 11

• crying signals the cortical regions
• signalling the hypothalamus
• stimulating the production of prolactin
• note PIH or dopamine
• prolactin encourages milk secretion from the mammary glands
• note also the action of oxytocin, released from the posterior pituitary
• stimulates smooth muscle contraction, assisting in the delivery of milk
• positive feedback from suckling baby enhances the ‘let down’ reflex, inhibiting PIH

Note that prolactinomas result in galactorrhea.
Hypopituitarism can result in difficulty breastfeeding.