Endocrinology Flashcards
What are the 7 major endocrine glands?
- Hypothalamus
- Pituitary
- Thyroid
- Parathyroids
- Adrenals
- Pancreas
- Reproductive (ovaries and testes)
What are the 3 classes of hormones?
- Proteins and peptides
- Amino acid derived
- Steroid
Give 3 examples from each hormone subtype (protein + peptide, amino acid, steroid)
- Proteins and peptides: oxytocin, growth hormone, FSH
- Amino acid derived: tyrosine, adrenaline, tryptophan
- Steroid: cholesterol, testosterone, aldosterone
What are the 4 main types of hormone receptor?
- G-protein coupled receptors
- Receptor tyrosine kinase (RTK) families
- Receptors associated with tyrosine kinase activity
- Steroid hormone receptors
What is the most common hormone receptor?
G-protein coupled receptors
Describe the extracellular, transmembrane and intracellular domains of the G-protein coupled receptors
Extracellular domain binds ligand (hormone)
7 transmembrane protein domain
Intracellular domain is associated with a G-protein complex which regulates signalling cascades
Why are GPCR’s so important in endocrinology? (2)
- Signals from the GPCR can be greatly amplified by downstream enzyme activity
- Many endocrine disorders are associated with defects in GPCRs e.g., loss of or gain of function mutations
Give an example of a GPCR and its ligand
Adrenoceptors are bound by adrenaline and noradrenaline
Give an example of a receptor tyrosine kinase family receptor
The insulin receptor
How does the insulin receptor work in terms of the extracellular, transmembrane and intracellular domains?
Extracellular domain binds insulin
Transmembrane domain is activated and dimerisation occurs i.e., the 2 symmetrical monomers bind
Intracellular tyrosine kinase domain is activated, resulting in autophosphorylation of tyrosine residues using Pi from ATP
What does phosphorylation of tyrosine residues in the RTK families result in?
It induces conformational changes and many downstream signalling effects within the cell
List 4 different downstream cellular effects that insulin receptor activation results in to reduce blood glucose
- Increased formation of glycogen, protein and fat
- Increased glucose uptake in tissues
- Increased utilisation of glucose
- Decreased glucose formation
Describe autocrine, paracrine and endocrine regulation
Autocrine: chemical released from the cell binds to receptors on the same cell
Paracrine: chemical released from the cell binds to an adjacent cell
Endocrine: chemical released into the bloodstream and travels to target cells
Cytokine receptors are an example of receptors associated with tyrosine kinase activity. Give a brief overview of how they work
Extracellular ligand binding phosphorylates the JAK/STAT pathway, resulting in alteration of gene transcription
Give 2 examples of cytokine receptors (a type of receptor associated with tyrosine kinase activity)
Prolactin receptor
Growth hormone receptor
Describe activation of steroid hormone receptors
- Steroid diffuses through the cell membrane and binds with receptor in either the cytoplasm or nucleus
- Steroid/receptor complex translocates to nucleus (if not already there) and binds to DNA response elements
- This results in altered gene transcription
Steroid receptors are usually found in the nucleus. Give an example of one which is found in the cytoplasm
Glucocorticoid receptors
The ?-? axis is the key regulator of most of the body’s hormones
Hypothalamic-Pituitary
Describe the Hypothalamic-Pituitary Axis
Neurons in the hypothalamus release hormones and factors which act on the pituitary gland (mainly the anterior) so that it releases its hormones
These hormones act on a target gland to produce peripheral hormones
These usually create a negative feedback loop to regulate their own secretion
What is the greatest determinant of hormone concentration when measuring hormones?
Rate of secretion
What is rate of hormone secretion determined by?
Feedback loops
What standard tests are done when measuring hormones in the blood?
- Thyroid hormones
- Steroid hormones
- Growth hormone e.g., cortisol
- Reproductive hormones
- Prolactin
- Ca2+ and parathyroid hormone
Describe the thyroid axis
- Hypothalamus releases thyrotropin releasing hormone (TRH)
- This stimulates the anterior pituitary to release thyroid stimulation hormone (TSH)
- This acts on the thyroid gland, causing it to release thyroid hormones
- Thyroid hormones and TSH act on the hypothalamus to inhibit TRH release, so regulate their secretion via negative feedback loops
In hypothyroidism, TSH levels are X and thyroid hormone levels are Y
X - TSH raised
Y - Thyroid hormone low
In hyperthyroidism, TSH levels are X and thyroid hormone levels are Y
X - TSH low
Y - Thyroid hormones raised
When might TSH not be a reliable marker of thyroid status?
- In the case of pituitary dysfunction e.g., pituitary tumour
- If the patient is systemically unwell with a non-thyroidal illness
Why is TSH measurement not useful in pituitary dysfunction or when a patient is sick with a non-thyroidal illness?
PD - anterior pituitary no longer releasing hormones properly
Illness - free thytropin hormone and TSH levels are lowered
Which tests are used to assess pituitary function?
- 9am cortisol
- Free thyrotropin (FT) hormone, TSH
- Prolactin
- Insulin growth factor 1 (IGF1)
- LH, FSH, E2/testosterone
- U&E, plasma/urine osmolality
In pituitary gland testing, a synacthen test may be used to assess…
Steroid hormone levels
Cortisol secretion from the adrenal cortex is regulated by…
-ve feedback loops acting on the anterior pituitary and hypothalamus (aka the hypothalamic-pituitary-adrenal (HPA) axis)
Why is cortisol taken as a 9am measurement?
Cortisol has a circadian rhythm, so peaks with waking and falls throughout the day
Hypothalamic-pituitary-adrenal (HPA) axis function can be assessed by a ? test
9am cortisol
Why is it hard to assess Growth Hormone Axis function?
Growth hormone production is pulsatile
Measurement of ? can indicate growth hormone hypersecretion
Insulin growth factor 1 (IGF1)
Briefly describe the reproductive axis (hypothalamic-pituitary-gonadal axis)
- Hypothalamus releases gonadotropin releasing hormones (GnRH)
- This stimulates LH and FSH release from the anterior pituitary (FSH in males, FSH and LH in females)