Endocrine Flashcards
Catecholines
Derived from tyrosine Noradrenaline, adrenaline, dopamin Insoluble - do not enter cells Exert their actions by binding to plasma membrane receptors Rapid onset
Thyroid hormones
Derived from tyrosine Thyroxine (T4) and tri-iodothyronin (T3) Lipid soluble and so can enter cells Receptors are located within cell nucleus Slow onset
Indoleamines
Derived from tryptophan
Serotonin, melatonin
Bind to plasma membrane receptors
Exert actions rapidly
Hypothalamus
Basal part of diencephalon
Appetite, HR, body temp, sexual appetite, stress response
Vascular link between median eminence and anterior pituitary
Somatostatin
Hypothalamus and delta cells of the endocrine pancrease
Potent inhibitor of GH secretion
Potential therapeutic to treat GH tumours
Thyrotrophin releasing hormone
Key regulator of TSH production in the pituitary
Dopamine
Catecholamine
Tonic inhibitor of prolactin secretion of pituitary
Corticotrophin releasing hormone
Key regulator of stress response
CRH mutations results in impaired stress response and front lobe epilepsy
Anterior posterior
Master gland
Controls function of numerous other glands
Situated in bony cavity at the base of the skull
5 cell types: gonadotroph, lactotroph, somatotroph, corticotroph, thyrotroph
Secretes: FSH, LH, GH, TSH, ACTH, PRL
Regulated by hypothalmic factors
Growth hormone
In response to GHRH and Ghrelin, inhibited by somatosytation
Effects on liver and muscle are mediated by the release of insulin-like growth factor
Acromegaly: GH-secreting tumour causing inappropriate growth, giantism and diabetes
GH insensitivity/deficiency: dwarfism, short stature, Laron’s syndrome
Thyroid stimulating hormone
Released in response to TRH stimulator and acts at thyroid gland to regulate the production of T4/T3 - regulate growth and metabolism
Thyrotropinomas: secrete high levels of TSH, treated by SST analogues, surgery and irradiation
TSH production is regulated by T4/T3 feedback at TRH neurons and at thyrotrophs
Prolactin
Secreted in response to TRH, oestradiol and VIP/PACAP and tonic inhibition by dopamine
Regulate lactation in oestradiol-primed mammary glands
Prolactinomas: cane be large - surgery
Adrenocorticotrophin hormone (ACTH)
Secreted from corticotrophs in response to CRH
Key regulator in stress response - regulates glucocorticoid production
Corticotrophinomas: Cushing’s syndrome - excessive glucocorticoid syndrome - surgery
Tpit mutations lead to ACTH deficiency - low glucocorticoids, weight loss, anorexia, low bp
Adrenal cortex
Paired gland, on top or near kidneys
Cortex: 80-90% gland volume
Medulla: 10-20%, highly vascularised
Zona glomerulosa: lies under capsule, 5-10% of cortex, cells are small and round, few lipid droplets, aldosterone
Zona fasciculata: 60-75% of the cortex, ZF cells are bigger than ZG, contains numbers of lipid droplets, cortisol
Zona reticularis: 20-30% of the cortex, intermediate size, relatively few lipid droplets, adrenal androgens
Actions of ACTH
Acute:
- Deplete ascorbic acid
- Stimulate steroid synthesis
- Increase blood flow to gland
Chronic:
- Increase adrenal weight
- Increase both cell number and size
- Induce synthesis of enzymes involved in steroid synthesis undos a consequence increase steroid synthesis
Transport of corticosteroids
In plasma bound vesicles to protein
Normal circulating volume: >90% of glucocorticoid are bound to transcortin or corticosteroid binding globulin (CBG)
Protein bound steroids - not biologically active
Aldosterone is not normally bound to specific proteins
Actions of glucocorticoids
Specific glucocorticoid receptor (GR)
Affects carbohydrate, lipid and protein metabolism
- Anabolic actions in the liver and catabolic actions in muscle and fat cells
- Protein breakdown and lipolysis (fat and muscle cells)
- Glycogenesis and gluconeogenesis (liver cells)
- Protein synthesis (liver cells)
Inhibit growth (young), anti-inflammatory, immunosuppressive, protection against stress, negative feedback on ACTH release
Clinical disorder of the adrenal cortex
Rare - usually female, middle aged - old dogs
Excessive quantities of glucocorticoids
Excessive secretion of cortisol may be due to increased secretion of ACTH
Cortisol excess due to hypersecretion of pituitary or extra pituitary-dependent hyperadrenocorticism (90%) or adrenal tumours (10%)
Actions of mineralocorticoids
Via specific mineralocorticoid receptors
Increase the reabsorption of Na in the kidney
Na ions are exchanged H and K ions leading to decreased Na and increased K excretion - increased acidity
No feedback effects on pituitary ACTH release
Aldosterone - excess primary hyperaldosteronism
Conn’s syndrome
Autonomous secretion of aldosterone due to presence of single adrenal adenomas in the zona glomerulosa
High levels of aldosterone:
- Hypertension - increase water and Na retention
- Hyperkalemia - muscle weakness, cardiac arrhythmias
Aldosterone - excess secondary hyperaldosteronism
Increased aldosterone secretion in response to increased levels of angiotensin II due to increased renin secretion from juxtoglomerular cells
Physiological reflex designed to conserve sodium in cases such as haemorrhage, salt and water depletion
ACTH stimulation test
Normal response: 2-3 fold increase over the pre-ACTH level of cortisol
Pituitary-dependent hyperadrenocorticism: exaggerated response (>660mmol/L)
Adrenal tumours: may hyper-respond or have very high resting cortisol levels with little or no change after ACTH
Addison’s: lack of response
Low dose dexamethasone suppression test
Normal response is a decrease in cortisol levels to
Steroids as treatment
Replacement for adrenal insufficiency
Anti-inflammatory therapy
Immunosuppressive therapy
Shock treatment
S/E: adrenal gland atrophy, hyperadrenocorticism, iatrogenic Cushing’s, PU/PD (ADH actions), polyphagia (anti-insulin effects), hepatomegaly (glycogen deposition in liver), fat deposition in abdomen, skeletal muscle weakness (muscle protein breakdown), thin skin and hair loss (effects on hair cycle and collagen synthesis)
