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)
At what time should the sex hormones be measured in males vs females?
Males - 9am testosterone due to circadian rhythm of testosterone peaking in early morning
Females - depending on timing in menstrual cycle (surge of LH and FSH mid-cycle due to release of egg)
Why is prolactin different from other hormones which are simulated by the hypothalamus?
Hypothalamus hormones (dopamine) inhibit prolactin release from the anterior pituitary rather than stimulate it
Prolactin acts on…
Prolactin receptors (PRLR) in breast tissue
Hyperprolactinaemia is a common reason for referral to endocrinology. What are some causes of hyperprolactinaemia?
- Pregnancy
- Lactation
- Nipple stimulation
- Tumours e.g., prolactinoma, pituitary, metastases
- Radiation
- Drugs e.g., antidepressants, anti-emetics, anti-psychotics
- Chronic renal failure
ADH release from the posterior pituitary results in…
Vasoconstriction and fluid reabsorption in the kidneys
This increases MABP
Name a disorder in which there is…
- Excess of ADH
- Lack of ADH
Excess - syndrome of inappropriate ADH secretion
Lack - diabetes insipidus
(both are life-threatening)
The main steroid hormones (A, B and C) are produced in the X and Y glands
A, B and C - aldosterone, cortisol and testosterone
X and Y - adrenal and reproductive glands
Defects in steroid hormone synthesis can lead to specific endocrine disorders such as…
Congenital adrenal hyperplasia
What are the 5 main principles for diagnosing any endocrine disorder?
- History and examination
- Biochemical screening tests
- Dynamic biochemical tests
- Imaging and specialised tests
- Treatment
What is meant by a dynamic biochemical test?
If there is a hormone in suspected excess, try to suppress it
If there is suspected deficiency in a hormone, try to stimulate it
Which endocrine gland has the highest level of endocrine control?
The hypothalamus
In what 3 ways does the hypothalamus control the neuroendocrine system?
- Secretes regulatory hormones which control the anterior pituitary
- Synthesises hormones and transports them to the posterior pituitary
- Direct neural control of adrenaline and noradrenaline secretion from the adrenal medulla
How are hormone levels controlled by diurnal influences? (2)
- External cues (light/dark) cause fluctuations in hormone secretions
- Hormone levels fluctuate depending on rate of elimination by the body
Hormones are grouped into what 3 classes based on their structure?
- Steroids e.g., oestrogens
- Amine-derived e.g., adrenaline
- Protein e.g., oxytocin, ADH, GH, insulin
The large majority of hormones are from which class?
Peptide hormone class
Describe steroid hormone synthesis
- Derived from cholesterol backbone
- Synthesis rate controls concentration
- Secreted once they are synthesised - they are not stored
Describe transport of steroid hormones
- Hydrophobic, lipophilic
- Transported in plasma by binding to carrier proteins (~90%)
Steroids are only active when bound to carrier proteins. T/F
False
Steroids are inactive when bound but active when unbound as they are free to binds to nuclear receptors
Various enzymes lead to different hormone formation from the cholesterol backbone.
Name 1 hormone involved in stress response and 4 hormones involves in sexual differentiation
Stress response: cortisol
Sexual differentiation: testosterone, progesterone, oestradiol, androstenedione
Give a brief overview of steroid hormone mode of action
- Lipophilic so pass through target cell plasma membranes
- Bind to nuclear receptors in cytoplasm or nucleus
- Hormone-receptor complex binds to DNA and alters gene transcription
Describe amine-derived hormone synthesis
- Derived from amino acids e.g., tyrosine
- Stored as vesicles in the cytoplasm until needed (unlike steroid hormones which need to be continuously secreted)
- Secreted from thyroid and adrenal medulla
Describe transport of amine-derived hormones
What is the one exception?
- Hydrophilic, lipophobic
- Transported unbound/free in blood plasma (except thyroid amine hormones which are bound to carrier proteins)
What type of receptors do amine-derived hormones bind to?
Membrane bound receptors e.g., GPCR
Describe peptide hormone synthesis
- Synthesised as precursor molecules and stored in secretory vesicles
- Different end hormones produced by cleaving with different enzymes
Which endocrine glands and organs secrete peptide hormones?
- Pituitary
- Parathyroid
- Heart
- Stomach
- Liver
- Kidneys
Describe transport of peptide hormones
- Hydrophilic, lipophobic
- Transported unbound/free in blood plasma
Peptide hormones may be arranged in rings or 2 chains, both joined by…
Disulfide bonds
Which hormone classes are transported free/unbound in blood plasma?
- Amine-derived hormones (except thyroid ones)
- Peptide hormones
Which hormone classes are transported via carrier proteins
- Steroid hormones
- Thyroid amine-derived hormones
List 3 benefits of transport via binding to carrier proteins
- Facilitation of hormone transport
- Increased half-life of hormone
- Act as a reservoir for the hormone e.g., steroid hormones aren’t stored in vesicles so carrier proteins are like a way to store them
Name 3 important specific carrier proteins
Cortisol-binding globulin (CBG)
Thyroxine-binding globulin (TBG)
Sex steroid-binding globulin (SSBG)
Name the hormones bound by…
Cortisol-binding globulin (CBG)
Thyroxine-binding globulin (TBG)
Sex steroid-binding globulin (SSBG)
Cortisol-binding globulin (CBG):
Cortisol
Thyroxine-binding globulin (TBG):
T4 (and some T3)
Sex steroid-binding globulin (SSBG):
Mainly testosterone and oestradiol
Name the 2 hormones secreted by the hypothalamus
Thyrotropin releasing hormone (TRH)
Corticotrophin releasing hormone (CRH)
What is the common target of TRH and CRH released from the hypothalamus?
Anterior pituitary
Describe the effects of TRH and CRH action on the anterior pituitary
TRH stimulates release of thyroid stimulating hormone (TSH) and prolactin
CRH stimulates release of adrenocorticotropic hormone (ACTH)
Name the 9 hormones secreted by the anterior pituitary gland
Thyroid stimulating hormone (TSH)
Adrenocorticotrophic hormone (ACTH)
Luteinizing hormone (LH)
Follicle stimulating hormone (FSH)
Growth hormone (GH)
Prolactin
Melanocyte stimulating hormone (MSH)
Oxytocin
Antidiuretic hormone (ADH)
What is the main target and function of thyroid stimulating hormone? (TSH)
Thyroid
Causes release of T3 and T4 which stimulate growth and metabolism
What is the main target and function of ACTH?
Adrenal cortex
Stimulates production of cortisol which is involved in the stress response
What is the main target and function of luteinizing hormone (LH)?
Gonads
Stimulates steroid release and ovulation from the ovaries
Stimulates testosterone release from the testes
What is the main target and function of follicle stimulating hormone (FSH)?
Gonads
Stimulates growth of ovarian follicles
Stimulates production of sperm (spermatogenesis)
What is the main target and function of growth hormone?
Liver, bones and muscle
Controls the body’s growth
What is the main target and function of prolactin?
Mammary glands (breasts)
Milk production and development of mammary glands
What is the main target and function of melanocyte stimulating hormone (MSH)?
Melanocytes
Protecting skin from UV light, development of pigmentation and controlling appetite
What is the main target and function of oxytocin?
Mammary glands and uterus
Stimulating childbirth and milk production (also involved in sexual arousal)
What is the main target and function of antidiuretic hormone (ADH)?
Kidneys
Promotes water reabsorption so less is passed out in the urine
What hormone is secreted by the pineal gland and what does it do?
Melatonin
Regulates circadian rhythm
Name the 3 hormones secreted by the thyroid gland
Thyroxine (T4)
Triiodothyronine (T3)
Calcitonin (CT)
What hormone is secreted by the parathyroid glands?
Parathyroid hormone (PTH)
Name 2 hormones secreted by the adrenal medulla
Adrenaline
Noradrenaline
Name 3 hormones secreted by the adrenal cortex
Dehydroepiandrosterone (DHEA)
Aldosterone
Glucocorticoids e.g., cortisol, corticosterone
Name 3 hormones secreted from the pancreas
Insulin
Glucagon
Somatostatin
Name 4 reproductive hormones
Testosterone (M/F)
Progesterone (F)
Oestriol (F)
Oestradiol (F)
Name 2 hormones secreted by the placenta
Human chorionic gonadotrophin (hCG)
Oestradiol
What hormone is secreted by the mammary glands?
Oestrogen
