Intro to Endocrine system Flashcards
What are the functions of the endocrine system?
Required for effective cell-cell communication in large, complex
multicellular organisms (~1014 cells in human body!!)
Monitor and coordinate internal environment and make
appropriate adaptive changes (homeostasis!);
Regulate growth, development, reproduction, senescence;
Enable you to respond and adapt to changes in external
environment (eg: food intake, water availability, temperature
change, “stressors”etc);
Define hormone
A chemical messenger produced and secreted by a specialized endocrine gland that is transported in the bloodstream to a distant target organ/cell where it elicits a physiological response
Name the THREE classes of hormone and give examples
Protein/peptide e.g Growth hormone (hydrophilic)
Cholesterol derivatives e.g. steroids(hydrophobic), Vit D(hydrophobic)
Modified amino acids e.g. Adrenaline (hydrophilic), Thyroid hormones (hydrophobic)
What are Circulating Hormone Levels Influenced by?
Rate of secretion
- by endocrine gland
Rate of metabolism
- by target tissue, blood, liver, kidney
Serum binding proteins?
- transport in blood - solubility issue etc
Name THREE ways hormone secretion is regulated?
Physiological changes
Endogenous rhythms
Feedback Mechanisms
Give examples of how hormone secretion is regulated by physiological changes?
- Blood glucose regulates insulin and glucagon release from pancreas
- Stress regulates adrenaline release from adrenal medulla
- Blood calcium regulates parathyroid hormone release from parathyroids
Give examples of how hormone secretion is regulated by endogenous rhythms?
- Ultradian - cycles in mins e.g. GnRH pulses (90-120mins)
2.Circadian - daily cycles e.g. testosterone (24 hr.)
cortisol (24h.)
- Infradian cycles- monthly
LH in females (~28 day menstrual cycle)
Give examples of how hormone secretion is regulated by feedback mechanism?
Mostly Negative (“closed-loop” feedback) - maintains homeostasis
Some Positive feedback
- e.g. milk-ejection reflex - involving oxytocin
pre-ovulatory LH surge - involving oestrogen
What are the types of endocrine dysfunction? (4)
Hyposecretion
Hypersecretion
Ectopic hormone secretion
End Organ Insensitivity/Resistance
What is ectopic hormone secretion?
hormone made outside normal endocrine gland (eg: Tumour)
What are the possible causes of hyPOsecretion? (6)
- Genetic e.g. Congenital adrenal hyperplasia
- Dietary e.g Iodine deficiency => thyroid malfunction
- Immunological e.g Hashimoto’s Disease & Addisons’s disease
- Cancer e.g Addisons disease
- Iatrogenic (Dr caused) e.g removal of parathyroid glands
- Idiopathic - unknown cause
What is the treatment for hyposecretion?
Hormone Replacement
Steroids or Thyroid Hormone
•Straightforward
•Absorbed in GI. Tract
•High Success
Protein Hormones •Difficult •Must be injected •Species specific –Human GH only for humans
What are some causes of HypERsecretion?
Functional tumour - e.g. Prolactin secreting pituitary adenoma
–Ectopic hormone-secreting tumour - e.g. Oat cell carcinoma of lung secreting ACTH => cortisol excess (Cushing’s Disease)
–Immunological - Grave’s Disease, antibodies that bind and activate TSH receptor on thyroid
Substance abuse - Anabolic steroid use, exogenous source of high hormone levels
What treatment options for hypersecretion?
•Surgical removal of the gland that is hyper-secreting
(but will then need replacement therapy!)
–e.g. Hyperthyroidism
•Irradiation of Gland – reduce function
(but will then need replacement therapy!)
–e.g. Hyperthyroidism
•Antagonists of the hypersecreted hormone
–e.g. ß blocker for pheochromocytoma
(NorAd/Adrenaline-secreting tumour of adrenal medulla)
What are the causes of end organ insensitivity/resistance? (2)
1. Genetic defect • e.g. Laron Syndrome • GH receptor mutation=> non-functional • normal/raised GH levels • Very low IGF
- Acquired Defect
•e.g. Type 2 Diabetes Mellitus
•impaired insulin receptor signalling
•Normal insulin levels, but compromised physiological response
Where is the pituitary gland found?
in bony cavity in base of brain case called the Sella Turcica
comprises 2 distinct lobes with different
embryological origins: posterior & anterior
What do hypothalamic parvoceullar peptidergic neurons control?
hormone secretion from Anterior Pituitary
What do hypothalamic magnocellular peptidergic neurons do?
directly innervate the Posterior Pituitary
e.g. hormones Vasopressin (ADH) and Oxytocin
How many types of Parvocellular hypothalamic neurones?
5 types controlling different endocrine cell types in Anterior pit
Where do the Parvocellular hypothalamic neurones terminate?
Neurones terminate in Median Eminence in close proximity to primary capillary plexus of Hypophyseal Portal System
How are the hormones discharged from Parvocellular hypothalamic neurones and what effect do they have?
Hypothalamic hormones discharged in a pulsatile manner
Most have stimulatory action on Ant. Pit.
Thus, termed “releasing hormones” or “releasing factors”
What does prolactin do?
Causes lactation
What does the H-P-Gonad/Testicular axis result in the production of?
Testosterone
What does the H-P-Ovary axis result in the production of?
GnRH stimulating FSH and LH
What are the effects of thyroid hormone? (4)
- Increases basal metabolic rate (BMR)
Raised O2 consumption, CO2 production, heat production - Cardiovascular system
Increases heart rate and force of contraction - Nervous system
Increases activity of sympathetic nervous system
Enhances the sensitivity to catecholamines - Growth and maturation (essential)
Embryo development
CNS development
Linear growth (promotes effects of growth hormone)
What controls the release of Growth hormone?
GHRH = + Somatostatin = -
Where is GH produced by? what does it do?
Produced by Somatroph cells in the Ant. Pit.
promotes growth of bone and muscles
Has metabolic effects on most tissues
What is the circulating half life of GH?
~20min
What are some direct actions of GH on tissues?
Generally antagonistic to insulin
1. Reduce glucose => increase plasma glucose
transport into cells
2. Increase lipolysis => increase plasma FFAs
- Increased amino acid transport into muscle => increase muscle growth
What are the indirect actions of GH as insulin-like growth factors? (IGFs I +II)
GH promotes IGF production by liver
IGF promotes:-
=> Linear growth of bones
(stimulates cartilage growth plates)
=> Growth/cell proliferation of soft tissues, viscera
Name the THREE disorders associated with growth hormone secretion
Hypopituitaryism/ Growth hormone deficiency in childhood - Dwarfism
Over secretion of growth hormone in children - Giantism
Over secretion of growth hormone in adult - Acromegaly
Treatment of growth hormone deficiency?
Replacement therapy with human GH.
Recombinant protein – Somatropin given by injection
Treatment of giantism?
Surgical removal of pituitary and/or suppression of GH secretion using somatostatin analogues lanreotide and octreotide.
Treatment of acromegaly?
Surgical removal of pituitary and/or somatostatin analogues or GH receptor antagonist – Pegvisomant.
What causes Laron syndrome?
Caused by mutation in GH receptor
Can be treated with IGF-1
Which hormones are secreted by the adrenal gland?
Adrenaline by the adrenal medulla
Cortisol & Aldosterone by the adrenal cortex
What is the function of Cortisol?
- Essential for adaptation to stress.
- Mobilizes glucose
-Anti-inflammatory actions (at high levels):
suppresses tissue responses to injury
decreases number of circulating lymphocytes
decreased antibody production
impaired cellular and humoral immunity
Cortisol modulates carbohydrate, fat and protein metabolism.
Opposes effects of insulin: in muscle, adipose and lymphoid tissues it is catabolic (in the liver it stimulates storage of glycogen (anabolic).
Increases plasma glucose levels by stimulating gluconeogenesis (synthesis of glucose from non-carbohydrate) in the liver.
Decreases glucose utilisation in other tissues.
Increased plasma glucose is used for the production of glycogen -important for the maintenance of liver glycogen during prolonged fasting.
What is the function of Aldosterone?
Maintains balance of Na/K in blood.
What is the HPA axis?
Negative feedback loop controlling cortisol secretion from adrenal cortex
What causes Cushings syndrome?
over production of cortisol
can be side effect of steroid medication
What are the symptoms of cushing syndrome? (5)
- Central obesity
- Thinning of the skin
- Bruising (due to capillary fragility)
- Hypertension (stimulates aldosterone production)
- Muscle and bone wasting
How is cushing syndrome diagnosed?
Measurement of cortisol/ACTH levels in urine/plasma.
Normal/very low ACTH concentration – ACTH independent e.g. adrenal tumour or the use of steroid medication.
High ACTH concentration - probably due to an ectopic ACTH-producing tumour.
Moderately high ACTH levels - tends to be due to a pituitary tumour
Dexamethasone suppression test: Low dose will suppress ACTH levels in normal patients but not in Cushing’s Disease. However, suppression often seen in high dose dexamethasone test.
Sample blood from inferior petrosal sinus. Blood from pituitary drains into here and can sample with a catheter – shows source of ACTH.
What are the treatment options for dysfunction of the HPA axis? (3)
- Reduce steroid medication
- Surgical removal of the tumour.
- Adrenalectomy - leads to high levels of POMC peptides due to lack of negative feedback - leads to hyperpigmentation - called Nelson’s syndrome.
What causes Addison’s disease? and what are the symptoms?
Lack of adrenal hormones - loss of adrenal function
Symptoms:
Tiredness & weakness
Anorexia & vomiting
Hypotension
Treatment for Addison’s disease?
Administration of mineralocorticoids such as 9a-fluorocortisol.
Administration of hydrocortisone to replace cortisol.
What is Vasopression (ADH) and what is its function?
A nonapeptide (oligopeptide formed from nine amino acids.) Reduces water excretion by kidney Is a potent vasoconstrictor
How long is the circulating half life of vasopressin?
~5 min
Circulates as free peptide and is cleared mainly by kidney
What is the main physiological stimulus of vasopression?
What else?
Main physiological stimulus = increased osmotic pressure of blood
Other stimuli: Fall in blood volume (>8%)(monitored by baroreceptors) Reduced arterial pO2 Raised arterial pCO2 Raised temperature Pain, trauma, infection
What happens when there is hyposecretion of ADH?
Include symptoms and causes
= Diabetes Insipidus
less water re-uptake (distal nephron)
- more urination
-increased plasma osmolality dehydration
Symptoms
Polyurea – copious, dilute urine (<20L/day!)
Polydipsia- thirst and excessive drinking
Causes
Neurogenic - brain/pit trauma
Nephrogenic – (kidney insensitivity)
Treatment for hyposecretion of ADH?
replacement therapy with Synthetic ADH analogue (Desmopressin)
As nasal spray. cab be given by injection
What happens when there is a hypersecretion of ADH?
=Syndrome of inappropriate ADH (SIADH)
Symptoms:
decrease in freq of urination
excessive fluid retention
Causes:
Physiological - cold, stress
Pathological - ADH secreting tumour
Treatment for hypersecretion of ADH?
Limit fluid intake to 500ml/day
Treatment with antibiotic Demeclocycline which has side effect of blocking action of ADH at kidney
What is Oxytocin and what is it used for?
Nanopeptide
Causes contraction of uterine smooth muscles
Which cells in the mammary glands respond to oxytocin?
Myoepithelial cells
What controls milk ejection?
Neuroendocrine relfex
involves a neuro-endocrine positive feedback loop
Where is Oxytocin produced?
magnocellular neurones
