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87 Cards in this Set
- Front
- Back
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Hormone (def)
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A hormone is a chemical signal released to influence the activity of another cell via a receptor
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qDifferent organisations of endocrine cells
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Gland - well defined region of them
Neurocrine systems - neurons that release hormones into the CNS and the blood Diffuse - endocrine cells dispersed |
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Types of endocrine communication
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Autocrine
Paracrine (via ECF to neighboring cell Endocrine - cell-blood-cell |
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Functions of endocrine systems
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Growth and differentiation control
Homeostasis responding to altered external environment Reproduction |
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Speed+duration of endocrine response
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release speed, half life, rapidity of action
Examples: Insulin very fast - draw graph of blood sugar vs insulin conc in the blood/adrenaline Cortisol release in development to control lung surfactant release |
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Feed forward control is always more positive than feedback control - why?
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Because always need to give response to stress no matter how high cortisol already is
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Hormone release
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Hydrophobic - diffuse out.
Hydrophillic - vesicles; Constitutive - protein containing vesicles released as produced - regulation via transcriptional regulation Regulated release = dense storage vesicles of hormone released in response to stimulus - faster and more direct method of release. |
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Protein hormones released as...
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...prohormones;
can have several copies of same hormone, or contain multiple hormones and cleaved before release (PMCH) |
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Amine hormone synthesis
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Tyrosine - L Dopa - Dopamine - NorA - Adr
(need large stores of Adr as it takes 20 hrs to make! |
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Transport of hormones...
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...hydrophilic in blood
hydrophobic = protein bound |
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Metabolism of hormones
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Hormones internalised with their receptor are degraded in lysosomes.
Steroid hormones degraded in liver E=liver failure = build up of estrogen in men and breast development! Hydrophillic hormones lost through kidney - E=kidney failure - build up of Prarathyroid hormone - increases breakdown of bone :S |
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There may be different sub-types of receptor for hormone on different cells
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ie. adrenaline/norA on alpha and beta adrenoceptors
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Principal types of receptors for hormone
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Ion linked - ie. Nicotinic ACh receptor
G protein linked - adrenergic receptors, glucagon receptor Enzyme linked - Tyrosine kinase receptor for insulin/growth hormone - autophosphorylates itself - allows phosphorylation of target proteins Intracellular receptors - control gene expression |
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Clinical evidence for GTPase
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Cholera toxin - covalently modifies Gs protein - permanently active because cant hydrolyse bound GTP - continuous intestinal secretion - diarrhoea and dehydration
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'Pertussin toxin
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Inactivates Gi protein - no inhibition of adenylyl cyclase.
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How turn off signal?
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Remove ligand (ie AChE)
Internalise receptor ligand complex - receptors uncoupoled in endosomes - lysosomes breakdwon hormones. Desensitisation of receptors Breakdown 2nd messenger - phosphodiesterase - cAMP Reversal of modification of target - Protein phosphatase/kinase |
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Intracellular receptors mechanism
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Hormone diffuses in, binds to receptor in nuc or cyt
receptor activated and migrates to transcription site binds to HRE (hormone response element in promoter region - regulatory part of gene - activates gene transcription |
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Pituitary dwarfism
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Inactivating receptor mutation for GHRH (growth hormone releasing hormone)
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Mutation causing activation of a receptor in absense of hormone ligand
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Activating mutation of LH receptor - precocious puberty
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Anti-receptor antibodies
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Deactivate receptor, or turn it on (CE Graves disease)
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Pituitary development
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Rathkes pouch grows up from oropharyngeal ectoderm (roof of mouth) forming Ant pituitary.
Infundibular process grows down from forebrain to form posterior pituitary Part of Rathkes pouch contacting infundibular process becomes intermediate lobe - cells become interspersed in ant pituitary in humans. |
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Pituitary vasculature
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Posterior lobe - internal carotid artery branches.
Ant Lobe - Hypothalamus gets blood from internal carotid artery - these then form capillary plexus gives rise to hypothalamo hypophysial portal vein - down to ant pituitary |
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Endocrine cells of Ant Pituitary
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Take Speed, Go Completely Loopy
Thyrotrophs, Somatotrophs, Gonadotrophs, Corticotrophs, Lactotrophs Glial like Folliculostellate cells surround and support the cells (E=can identify them by immunocytochemistry(antibody labelling)) |
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Regulation of Adenohypophysis
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By neurohormones from hypothalamus
Always stimulatory except PRL Pulsatile release from Hypothalamus makes release pulsatile too Negative feedback by systemic hormones Paracrine action within ant pit. |
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Pituitary tumour
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because Tumour enclosed in SPHENOID bone - can only grow upwards - into brain. Affects vision because puts pressure on the optic nerve
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Neurohypophysis
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Formed by exons and terminals of neurosecretory neurones of Hypothalamus
Pituicytes (type of glial supporting cell) surround and support the terminals Vasopressin and Oxytocin; Made in hypothalamus - packed into granules and sent down axons exocytosed into jugular vein in neurohypophysis. Regulation entirely by hypothalamus |
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A hormone derivative needed for the development of the male genitalia
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dihydrotestosterone
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TSH
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Glycoprotein from Adenohypophysis
acts on G protein receptors on thyroid cells - increased thyroid hormone sercretion - increases metabolic rate. Release in response to cold/stress |
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ACTH
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Adrenocorticotrophic hormone
Polypeptide hormone from POMC prohormone (all prohormones for protein hormones) From coticotrophs of ant. pit. Acts on G protein receprotes Stimulates; -cortisol release from Zona Fasciculata of adrenal cortex. -growth of adrenal cortex In response to stress/hypoglycaemia |
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Excess ACTH?
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Leads to excess glucocorticoid - Cushings disease;
Hypertension, osteoporosis, infertility |
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Too little ACTH?
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Addisons disease - low blood pressure
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LH
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Glycoprotein
G protein receptor synthesis of sex steroids by ovary control of testosterone production |
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FSH
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From Gonadotrophs of ant pituitary
Stimules Follicle growth/sperm production via G protein |
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Pathologies of gonadotroph hormones
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Deficiency - Infertility, lack of sexual maturity
Excess - precocious puberty |
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Prolactin
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Protein hormone
Released from Lactotroph cells of Ant.Pituitary Stimulates; -breast development and milk production -inhibits reproductive function Stimulated release by - suckling, also by stress - this reduces dopamine release from hypothalamus - dopamine suppresses prolactin release. |
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Prolactinoma
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Prolactin releasing tumour
Infertility and impotence |
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Somatotroph cells
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Secrete growth hormone - Protein hormone
Activates receptor linked tyrosine kinase Stimultaes; -long bone and soft tissue growth both by direct action and also by causing release of IGFs from liver Also stimulates protein synthesis and raises blood glucose |
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Excess and deficiency of GH
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Before epiphyseal plate fusion;
Excess; Giganticism Deficit : Short stature Acromegaly : excess GH secretion after puberty |
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ADH
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/Vasopreesin - released from Neurohypophysis - (made in hypothalamus) - peptide hormone
G protein receptors (V1 and2) Increase water reuptake in collecting ducts of kidney (V1) (detected by hypothalamus osmoreceptors |
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Diabetes insipidus
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2 types; renal and Hypothalamic.
Renal=lack of ADH action Hypo=lack of ADH production Dehydrates as too much water loss E. Transgenic mouse - mutation for ADH - high urine output. |
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Oxytocin
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Released from post. pit.
Receptor PLC coupled (Gq) Stimulates; -contraction of uterine muscle during childbirth - stimulated release by vagina/cervix stretch at parturition(labour) -Milk ejection by contraction of breast myoepithelium - stim by suckling |
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Evidence for action of Oxytocin
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Deficit = prolonged labour
Knockout mouse - no milk ejection |
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Pancreas development
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Develops from endoderm of gut tube
Cells bud off pancreatic duct to for islets of langerhans TFs cause differentiation of endocrine cells Abnormal proliferation of insulin cells in babies = hypoglycaemia |
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Pancreas makes...
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...glucagon - alpha
insulin - beta somatostatin - gamma |
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Blood supply and innervation
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Rich arterial blood supply from the coeliac and superior mesenteric arteries.
Venous drainage into liver via hepatic portal vein. Rich innervation by ANS |
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Insulin
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Protein hormone (released as prohormone)
Release by mechanism; inc glucose thru Glut2, inc ATP production, ATP inhibits ATP dep K+ channel - depolarisation - Ca2+ entry - exocytosis triggered Tyr Kin receptor - IRS protein - signal cascade Promotes anabolism CE Insulinoma |
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Diabetes mellitus
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Type 1 - no insulin production - autoimmune destruction of pancreatic beta cells
Type 2 - receptor down regulated as too much insulin as too much sugar in diet |
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Sulphonylurea drugs
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Inhibit ATP dependant K+ pump - therefore depolarisation, calcium entry, exocytosis of insulin containing vesicles
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Glucagon
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From panc. alpha cells
Peptide (released as proglucagon) -low secretion - stim glycogenolysis -med - stim gluconeogenesis -high - lipolysis , beta ox and ketogenesis |
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Glucagonoma
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hypergluconaemia
hyperglycaemic diabetes mellitus |
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Somatostatin
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Peptide hormone from gamma cells of panc.
G protein coupled receptor. Paracrine action to reduce secretion of insulin and glucagon CE Somatostatinoma - symptoms of diabetes - via insulin suppression |
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Pancreatic polypeptide
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From exocrine region and islets
Stimulated by : hypoglycaemia Inhibits exocrine pancreas release of enzymes Blocks gall bladder contraction |
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Multiple endocrine neoplasia
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Multiple tumours
MEN type 1 - Tumours of Parathyroid, pancreas and pituitary MEN type 2 - tumours of calcitonin secreting cells of thyroid, adrenal medulla and PTh gland |
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Thyroid development
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Thyroid diverticulum forms in midline of the floor of the mouth between 1st and 3rd brachial arch components of developing tongue.
Grows caudally over developing larynx to ant. aspect of trachea. As it descends - associates with the superior /inferior Parathyroid (develops from 3rd and 4th pharyngeal pouches and neural crest cells which form calcitonin/parafollicular cells) 2 Lateral lobes and a central isthmus formed - tissue along line of descent usually disappears |
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Thyroid anatomy
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Isthmus - central part = ant. to 2nd -4th tracheal rings
Lateral lobes extend up either side of trachea and larynx Enclosed in pre-tracheal fascia - attaches it to trachea - moves on swallowing Perfuse blood supply and venous drainage |
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Control of thyroid hormone secretion
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Hypothalamus releases TRH (in response to high plasma glucose and low core temperature)- controls TSh secretion from ant. pituitary
TSH stimulates thyroid to release T3 and T4 (negative feedback) |
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Production of T3 and T4
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Controlled by TSH and Iodide levels (unlike most endocrine glands - thyroid stores large amounts of hormone precursor extracellularly)
Cuboidal epithelial cells (follicular cells) arranged in follicles -lumen full of colloid. The follicular cells synthesis thyroglobulin which is then released into the colloid.(active thyroid - cells more columnar and colloid smaller) Na+I- symporter on basal membrane Iodide ions oxidised on apical membrane by enzyme. Iodine then able to iodinate tyrosyl residues on thyroglobulin and couples tyrosyl residues creating T3 and 4, however inactive - because still bound to thyroglobulin. Colloid = store of thyroglobulin. TSH stimulates endocytosis of throglobulin and its degradation in lysosomes to release t3/t4 |
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Parafollicular cells
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Thyroid - next to follicular cells - release calcitonin (acts to raise lowered plasma Ca2+
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Plasma transport of T3/4
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bound to plasma proteins;
thyroxine binding globulin albumin increases half life |
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Diff between T3 and 4
and how interconverted? |
Extra iodine on T4
More T4 released but T3 much more active - activated in liver T4 to T3 by type 1 deiodinase (amount of deiodination reflects need for metabolism) (T4 to T3 also in pituitary - important for -ve feedback) T4 can also be converted to inactive rT3 |
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Breakdown of T3
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finally deiodinated to thyronine
iodide salvaged by kidney and reused |
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T3 mech of action
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Act on TR (nuclear receptor) - acts on TRE's (sensitivity to T3 controlled by number of TRs)
Increases basal metabolic rate |
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How does T3 acheive it's effect?
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Inc activity of RNA polymerase!
Increase the effects of Beta adrenoceptors on glycogenolysis and gluconeogenesis, AND INSULINs effect on the reverse processes! Increase cholesterol synthesis and breakdwown Stimulate bone turnover Stimulate gut motility Inc heart rate Inc production of Beta adrenoceptors Increase transcription of NaKATPase |
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Developmental effects of T3
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Essential for postnatal growth of CNS; stimulates NT and myelin production, and axonal growth
Also stimulates linear growth of bone by affecting chondrocytes Normal development of teeth, hair, epidermis |
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Goitre
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Swelling of thyroid - due to iodine deficiency - no T3/4 production so no negative feedback so thyroid swells
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Hyperthyroidism
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Graves disease (high T3)
Raised BMR, fast pulse, weight loss despite appetite, heat intolerance, eye protrusion Caused by autoimmune production of immunoglobulins that mimic TSH (tumours can also cause hyperthyroidism) |
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Hypothyroidism
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In Neonate - cretinism - gross deficit in myelination and stunting of postnatal growth.
Adult - myxoedema - reduced metabolism, hypothermia, constipation Can be due to thyroid hormone receptor mutation. |
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Treating hyperthyroidism
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Give iodine - large doses - reduce activity/vascularity of the gland
Radioactive iodine - destroy some thyroid tissue by local irradiation |
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Parathyroid glads
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Secrete Parathyroid hormone - peptide hormone secreted in response to low Ca2+
Principal control of Ca2+ PTH secreting tumour - bone breakdown - urinary stones |
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Development of Adrenal glands
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Medulla from neural crest tissue
Cortex from intermediate mesoderm. Adrenal glands identifiable as separate organs when they develop fetal and definitive zone at 2months after gestation. Fetal zone = very prominant in fetus however regresses after birth - important to produce weak androgens that the placenta changes to oestrogen Definitive - more similar to adult cortex |
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Microstructure of adrenal
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Medulla:made up of groups of chromaffin cells packed with catecholamine granules - store large amounts of NorA/Adr
Cortex - balls and sheets of cells in 3 zones |
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Zones of Adrenal cortex and their products
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Outer - Zona Glomerulosa - Aldosterone
Middle - Zona Fasciculata - Cortisol Inner - Zona Reticularis - androgens |
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Blood supply to adrenal
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Richly vascularised; Arteries from phrenic artery, renal arteries, and directly from aorta.
- these form arterial plexius beneath adrenal and enter a sinusoidal system that penetrates both cortex and medulla - draining into the adrenal vein which drains into IVC and Renal vein. (unlike most splanchnic arteries, the blood flow to the adrenal dilates under stress |
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Sinusoid?
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A fenestrated cappillary
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Innervation of adrenal
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Preganglionic sympathetic fibres acting on nicotinic receptors of chromaffin cells with ACh stimulating catecholamine release
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Adrenal medulla
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Role:reaction to acute stress
Synthesis adrenaline/NorA and store in vesicles Act on Adrenergic receptors around body to cause vasoconstriction via alpha 1 (PLC), Vasodilation in skeletal muscle via Beta receptors - also heart inc chrono and ino-tropy, also via B - dilate bronchi |
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Adrenal medulla pathology
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Remove it - no worries because rest of sympathetic compensates
Tumour that secretes - hypertension, tremor, anxiety |
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Adrenal cortex - synthesis of steroid hormones?
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Cholesterol dtored in lipid droplets in cell
transported to mitochondria - where steroid hormone production occurs Hormone produced depends on enzymes expressed in cells |
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PLasma transport of steroid hormones
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Albumin binds all
Cortisol binds cortisol binding globulin with inc affinity (therefore increased half life) |
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Metabolism of steroid hormones
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Kidney filters free steroid hormone - but reabsorbs 90%
Liver converts them to hydrophillic metabolites by hydroxylation and conjugation CE liver disease = increased cortisol |
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Cortisol
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Receptors = GR (present in nearly all cells
Metabolised in liver to relatively inactive cortisone Control of secretion; Hypothalamus release CRF in response to stress. Acts on pituitary to stimulate corticotrophs to produce and release ACTH (cleaved from POMC precursor) which then stimulates Zona Fasciculata to fproduce cortisol Action - Provide protection for the body during prolonged stress - primarily to preserve glucose for brain. (inc gluconeogenesis, lipolysis, ketogenesis, protein breakdown...inc heart contraction, inc RBC production in long bones - inc O2 capacity, inhibit reproductive function) |
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Aldosterone
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Acts on MR
increases transcription of ENaC channels and Na+K+ATPase - so increase ion and water reuptake - |
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Control of aldosterone output
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Renin angiotensin system....
Low Na+/BP JGA stimulated to release renin. Renin breaks down angiotensin to angiotensin 1, which is then converted to A2 by ACE in the lungs. A2 then stimulates Aldosterone output from zona glomerulosa (also stimulates thirst and arteriolar constriction) |
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Hypoaldosteronism
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Causes excessive Na+ loss, decreased blood volume and therefore BP.
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Conns syndrome
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(hyperaldosteronism) excessive Na+ retention, increased blood volume, increased BP
Spironolactone - antagonist can be used to reduce affinity of aldosterone - antihypertensive - also ACE inhibitors (Hyperaldosteronism can be mimicked by cortisol if such high concentration to overcome the deactivating enzyme present and affect MR receptors. |
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Adrenal androgens
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DHEA - by zona reticularis
Stimulates pubic/axillary hair growth and libido Release stimulated by ACTH (DHEA sulphate main product of fetal adrenal) |
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Congenital adrenal hyperplasia
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Mutations in enzymes involved in steroid synthesis can occur
CE most common - 21-hydroxylase - decreases cortisol secretion - salt loss - increased ACTH (because negative feedback removed) so adrenal hyperplasia, excessive androgen formation - virulises female fetuses |
