Endocrine Physiology Flashcards
What is the endocrine system?
A system that controls function via the secretion of hormones which are carried in the blood to target organs
What is endocrine and exocrine?
Endocrine- ductless
Exocrine- ducted
What is autocrine and paracrine?
Autocrine- cells secrete chemicals that bind to receptors on same cell
Paracrine- chemicals diffuse in ECF to affect neighbouring cells
What are the 3 types of endocrine hormone?
Peptide hormones
Amine hormones
Steroid hormones
What are examples of peptide hormones?
TRH
FHS
Insulin
How are peptide hormones synthesised?
- Preprohormone formed by amino acids
- Enzymes in the ER form inactive prohormone
- Prohormone passes from ER through golgi apparatus
- Secretory vesicles containing enzymes and prohormone bud off golgi
- Enzymes chop prohormone into active peptides and peptide fragments
- Vesicles release contents by exocytosis
- Hormone moves into circulation
What is C-peptide?
Inactive fragment cleaved from prohormone
What is the clinical relevance of C-peptide?
Levels of c peptide measured to indicate endogenous insulin production
Which 2 amino acids are amine hormones derived from?
Tyrosine
Tryptophan (melatonin)
Which hormones have a similar action to peptide homrones?
Catecholamines (hydrophilic)
Which hormones have a similar action to steroid hormones?
Thyroid hormones (lipophilic)
What are steroid hormones derived from?
Cholesterol
What is the action of steroid hormones?
Translation produces new proteins for cell processes
What is the adenohypophysis?
Anterior pituitary
How is the anterior pituitary connected to the hypothalamus?
Hypothalamic-hypophyseal capillary portal system
What is the neurohypophysis?
Posterior pituitary
How is the posterior pituitary connected to the hypothalamus?
Continuation of hypothalamus axons and nerve terminals
What separates the anterior and posterior pituitary?
Pars intermedia
What are non tropic hormones?
Hypothalamus to posterior pituitary to blood
- Vasopressin (ADH)
- Oxytocin
What are tropic hormones?
Hypothalamus to anterior pituitary. Govern release of AP hormones
- TRH
- CRH
- GHRH
- GHIH
- GnRH
- PRH
- PIH (dopamine)
What does TRH control?
TSH
Prolactin
What does CRH control?
ACTH
What does GHRH and GHIH control?
GH
What does GnRH control?
FH and LH
What does PRH and PIH (dopamine) control?
Prolactin
What is the glucostatic theory?
Food intake is determined by blood glucose
What is the lipostatic theory?
Food intake is determined by fat stores
What is an absorptive state?
Anabolic phase after eating
What is a post-absorptive state?
aka fasting state
Catabolic phase between meals
What is normal range for [BG]?
4.2-6.3mM (5mM)
What are the anabolic actions of insulin?
Lowers [BG]:
- Glycogenesis
- Lipogenesis
- Protein synthesis
- Glucose oxidation
What are the catabolic actions of glucagon?
Raises [BG]:
- Glycogenolysis
- Gluconeogenesis
- Ketogenesis
What do a cells produce?
Glucagon
What do B cells produce?
Insulin
What do d cells produce?
Somatostatin (GHIH)
What do PP cells produce?
Pancreatic polypeptide
What is the mechanism of insulin secretion?
- Glucose enters B cell through GLUT transporter
- This increases [ATP] by CAC
- increased ATP causes K-ATP channel to close
- K+ levels rise, depolarising the cell
- Calcium channels open
- Triggers vesicle exocytosis
What is the mechanism of insulin action?
- Insulin binds to tyrosine kinase receptors on muscle and adipose tissue
- Stimulates mobilization of GLUT4 transporters to cell membrane
- Glucose enters the cell
What tissues are insulin depndent?
Muscle
Adipose
How does the liver use insulin?
Not insulin dependent
GLUT2 transporters
Presence of insulin enhances glucose uptake into hepatocytes by creating a conc. gradient
What stimuli increases insulin release?
High [BG]
Increased [AA]
Increased glucagon
Increased [gastrin, secretin, CCK]
Vagal nerve activity (Parasympathetic)
What hormones form part of the glucose counter-regulatory control system?
Glucagon
Epinephrine
Cortisol
Growth Hormone
What stimuli increases glucagon release?
Low [BG]
High [AA]- prevents hypoglycaemia from insulin release
Sympathetic innervation
Cortisol and stress
What is the action of somatostatin?
Inhibit activity in GI tract
Suppresses release of both insulin and glucagon (paracrine)
What is the effect of exercise on [BG]?
Entry of glucose into skeletal muscle is increased despite insulin absence
- GLUT4 transporters migrate without insulin being present
What 3 factors affect growth?
Genetics
Nutrition
Hormone
What are the 2 periods of rapid growth?
Infancy- TH, insulin, GH
Puberty- androgens, GH
When does GH becomes significant?
Around 10 months
What is the effects of TH on GH?
Permissive effect
Low TH will cause reduced GH action
What is growth hormone?
aka Somatotropin
Anabolic hormone
What neurohomrones control GH release?
GHIH (somatostatin)
GHRH
What are the actions of GH?
Growth of long bones
- Intermediate is IGF-1
Regulation of metabolism
- Anti-insulin effect
- Increases BG
What receptors does GH act on?
Tyrosine kinase receptors
Phosphorylates intracellular targets
What is IGF-1?
Insulin like Growth factor, aka Somatomedin C
Stimulates glucose uptake in muscle and in bone
Released by liver in response to GH
What stimuli increases GHRH secretion?
Reduced energy supply (fasting, exercise, hypoglycaemia)
Increased amino acids
Physical stress and illness
Delta sleep
Sex homrones
What stimuli increases GHIH secretion?
Glucose
Free fatty acids
Ageing
Cortisol
What conditions are caused by hypersecretion of GH?
Gigantism
Acromegaly
What conditions are caused by hyposecretion of GH?
Deficiency of GHRH (hypothalamus)
Deficiency of GHIH (pituitary)
Precocious puberty
Hypothyroid dwarfism
What are the 2 thyroid hormones?
T3- triiodothyronine
T4- thyroxine
What are the 2 thyroid gland cell types?
C cells- secrete calcitonin
Follicular cells- support TH synthesis
How are THS synthesised?
- Thyroglobulin made in follicular cells and secreted into colloid with enzymes (thyroxidases)
- Iodide enters follicular cells via symporter with NA+
- Follicular cells concentrate iodide and transport it to colloid via pendrin transporter
- Thyroxidases oxidase iodide to iodine
- Iodine combines with tyrosine residues on thyroglobulin to form thyroid hormones
- TSH stimulates endocytosis of enzymes and thyroglobulin back into follicular cell
- Proteolytic enzymes cut thyroglobulin to release T3 and T4
- T3 and T4 pass into plasma and bind to thyroxine binding globulin
What thyroid hormone is more physiologically active?
T3 as receptors have a higher affinity
T4 is deiodinated to T3 by deiodinase enzymes in plasma
Which hormones regulate TH release?
TRH (thyrotropin releasing hormone) from hypothalamus
TSH (thyroid stimulating hormone) from AP
What is the action of TH?
Increases metabolic rate and promotes thermogenesis
Increases gluconeogenesis
Increases proteolysis
Increases lipolysis
Stimulates GH expression (growth)
Brain development in utero
What does the adrenal medulla release?
Secretes catecholamines:
- Epinephrine
- Norepinephrine
What does the adrenal cortex release?
Secretes steroid hormones:
1. Zona gomerulosa- aldosterone
2. Zona fasciculata- cortisol
3. Zona reticularis- testosterone
Which enzyme is important in aldosterone and cortisol synthesis?
21- hydroxylase
Lack causes adrenal hyperplasia
Which hormones control cortisol release?
CRH from hypothalamus
ACTH from AP
What is the action of cortisol?
Glucocorticoid: increases BG
- Gluconeogenesis
- Proteolysis
- Lipolysis
- Decreases insulin sensitivity
What is the action of aldosterone?
Increases Na+ reabsorption (and water)
Increases K+ excretion
Secretion is controlled by RAAS
Therefore effects blood volume and BP
What are the roles of calcium in the body?
Signalling
Blood clotting
Apoptosis
Skeletal strength
Membrane excitability
What is the effect of hypocalcaemia on neurones?
Increases Na+ permeability leading to hyperexcitation
What is the effect of hypercalcemia on neurones?
Decreases Na+ permeability leading to reduced excitability
What is the calcium distribution in the body?
99% bone
0.9% intracellular
0.1% ECF
Describe calcium in the ECF
Ca2+ plasma is 2.4 mM
40% protein bound
10% complexes to an anion
50% free (1.2mM)
What hormones increase calcium?
PTH- parathyroid hormone
Calcitriol- active form of vitamin D
- aka 1,25- dihydroxycholecalciferol
What hormone decreases calcium?
Calcitonin- released from C cells of thyroid gland
What is the action of PTH?
Increases [Ca2+]
- Increases bone reabsorption
- Increases kidney reabsorption of calcium
- Increases renal excretion of phosphate so calcium is not deposited back in bone
- Stimulates calcitriol release
What is the action of calcitriol?
Increases [Ca2+]
- Increases intestinal absorption of calcium
Which hormone stimulates calcitriol in lactating women?
Prolactin
- Increased demand for Ca2+ for milk production in lactation
What is the action of calcitonin?
Decreases [Ca2+]
- Decreases bone reabsorption
- Increases renal excretion of calcium
