Introduction et notions de base endocrinologie Flashcards
What is endocrinology?
The branch of medicine that studies hormones
What is a hormone?
Molecule produced by a cell in response to a precise stimulus which is liberated and then stimulates a specific cell with a specific receptor.
What are the principal endocrine glands?
- hypothalamus-hypophysis
- parathyroid
- thyroid
- adrenal glands
- pancreas
- testicles/ovaries
Can also be other things:
- adipose tissue
- heart
- kidneys
- skin
- thymus… etc.
What is the endocrine effect?
Hormone is released from a cell into the blood. through which it travels to the target cell
What is the paracrine effect?
Hormone is released and stimulates neighbouring cell
What is the autocrine effect?
Hormone is released and has effect on that same cell (auto-modulation)
Overview of autocrine, endocrine, and paracrine
What are the principal hormones released by the hypothalamus and their general effects? (8)
Called libérines:
- CRH (corticotropin-releasing hormone): stimulates ACTH
- GHRH (growth hormone-releasing hormone): stimulates GH
- GnRH (or LHRH) –> gonadotropin-releasing hormones: stimulates LH and FSH
- TRH (thyrotropin-releasing hormone): stimulates TSH
- Somatostatin: inhibits GH
- Dopamine: inhibits prolactin
- Oxytocin and vasopressin (ADH): go towards neurohypophysis to be secreted
What are the principal hormones released by the pituitary gland? (7)
Anterior pituitary:
- ACTH (adrenocorticotropic hormone)
- GH (growth hormone)
- FSH and LH (follicle-stimulating hormone and luteinizing hormone)
- TSH (thyroid-stimulating hormone)
- PRL (prolactin)
Posterior pituitary (neurohypophysis): synthesized by hypothalamus and released by posterior pituitary
- ADH
- Oxytocin
What are the principal hormones released by the thyroid? (3)
- T4 (thyroxine)
- T3 (triiodothyronine)
- Calcitonin
What are the principal types of hormones released by the adrenal glands? (4)
- Glucocorticoids (ex: cortisol)
- Mineralocorticoids (ex: aldosterone)
- Catecholamines
- Androgens
What are the hormones released by the pancreas? (2)
- Insulin
- Glucagon
What hormone is released by the testicles?
Testosterone
Which hormones are released by the ovaries?
- Estrogen
- Progesterone
- Androgens
Which hormone is released by the parathyroid gland?
PTH (parathormone) –> phosphocalcic effect
What kinds of hormones are hydrosoluble? (4)
Proteins, polypeptides, glycoproteins, and amines
Which hormones are hydrosoluble? (19)
Hypothalamus:
- CRH, GHRH, GnRH, TRH, somatostatin, and dopamine
Pituitary gland:
- ACTH, GH, FSH, LH, TSH, prolactin, ADH, oxytocin
Parathyroid and thyroid:
- PTH and calcitonin
Pancreas:
- Insulin and glucagon
Adrenal glands:
- Catecholamines
What are the 6 steps of hydrosoluble hormone synthesis?
- Gene activation
- DNA transcription
- mRNA formation
- mRNA translation –> protein (ribosomes)
- Maturation of polypeptide (ER and golgi –> pre-pro/pro)
- Exocytosis –> secretion
What is a preprohormone?
precursor protein to one or more prohormones
- pre radical allows the protein to anchor in the membrane of the ER
- this radical is cleaved to form a prohormone
What is a prohormone?
hormone + radical that migrates into the Golgi body which will later be cleaved by endopeptidases in the secretory vesicle to form the active hormone
Overview of prepro, pro, and active hormones:
What are 2 examples of clinical uses of prohormones?
- peptide C –> sécrétion endogène d’insuline
- hyperpigmentation (maladie d’Addison)
What is peptide C?
useful for measuring endogenic insulin production since they’re produced in a 1:1 ratio in the body therefore should be present in similar amounts in the blood
How does hyperpigmentation in Addison’s disease work?
Addison’s disease = primary adrenal insufficiency which causes a decrease in cortisol production
- this decrease causes an increase in CRH and ACTH production to try to increase CORT production and since there is no negative feedback from CORT levels
- gamma-MSH is produced when producing ACTH, therefore when production of one is increased so is the other
- this leads to increased melanocyte production which causes hyperpigmentation
- gamma-MSH is produced when producing ACTH, therefore when production of one is increased so is the other
What is the “secretion pattern” of hydrosoluble hormones?
Periodic and rhythmic
The rhythm varies and can either be:
- pulsatile
- circadian
- monthly (ex: menstrual cycle/TSH and LH levels)
How are hydrosoluble hormones secreted and transported?
Secreted:
- Stored hormones are first released from granules (FAST)
- Causes increased synthesis which takes a bit longer
Transport:
- Not bound to anything therefore quite short half-life
- Cannot be taken by mouth because they would be digested by proteases
- This explains why you can’t take pill versions of these hormones and they must be injected.. ex: insulin
How do hydrosoluble hormones work?
Stimulate membrane receptors since they cannot enter cells
Two main kinds of receptors:
- G-protein coupled receptors
- Tyrosine kinase receptors
How do G-protein coupled receptors work?
- Hormone binds to receptor on cell membrane
- G-protein is activated
- G-protein interacts with effector proteins
- ex: adenylate cyclase, phospholipase C, and phosphodiesterase
- Effector proteins produce second messengers which amplify signal
- Adenylate cyclase: inc. cAMP
- Phospholipase C: IP3, DAG, and calcium
- Phosphodiesterase: dec. cAMP
- These second messengers lead to the regulation of 1+ proteins which lead to the biological response
Which hormones use G-protein coupled receptors?
Adenylate cyclase activation:
- Epi/norepi (beta receptors)
- Calcitonin
- PTH
- ADH, ACTH, FSH/LH, TSH
- Glucagon
Phospholipase C:
- Epi/norepi (alpha-1)
- Oxytocin
- Others…
Adenylate cyclase inhibition:
- Epi/norepi (alpha-2)
How do tyrosine kinase receptors work?
- Hormone binding to receptor leads to creation of dimer/structural change which activates tyrosine kinase
- Tyrosine kinase phosphorylates relay proteins which starts intracellular cascade/response
TK can either be:
- Intrinsic: on receptor itself
- Extrinsic: within the cytoplasm of the cell (JAK-STAT)
Which hormones use tyrosine kinase receptors? (4)
- Insulin
- IGF-1 and IGF-2
- Prolactin
- GH
1 and 2 –> intrinsic TK
3 and 4 –> cytoplasmic TK
What are the two kinds of liposoluble hormones?
- Stéroïdes
- Type stéroïdes
What are the three kinds of steroid hormones and the two kinds of “type stéroïde” hormones?
Steroid:
- Ovarian (estradiol, progesterone)
- Testicular (testosterone)
- Corticosurrénales (cortisol, aldosterone, DHEAS)
Type stéroïdes:
- Thyroid hormones (T4 and T3)
- Vitamin D
How are steroids synthesized?
- Cholesterol is stored in lipidic vacuoles
- Cholesterol is transported to mitochondria
- (StAR: steroidogenic acute regulatory peptide)
- Intra-mitochondrial synthesis of cholesterol metabolites (enzymes)
- Diffusion towards endoplasmic reticulum –> conversion into active hormones
- Active hormones diffuse towards the cell membrane towards circulation
What does steroid hormone formation depend on?
Depends on the location in which the hormone is created, but they’re all from cholesterol
What are the five steps of thyroid hormone production?
- Capture iodine
- Thyroglobuline synthesis
- Iodine fixation (3 or 4 depending on hormone)
- Couplage
- Stockage
- Sécrétion
How are liposoluble hormones secreted and transported?
Secreted:
- Diffusion
- Secretion controlled by synthesis
- Not many intracellular reserves
- Rhythmic/cyclic
Transport:
- bound to proteins
- ex: CBG, SHBG, TBG, albumin
How is the amount of circulating liposoluble hormones controlled?
Fraction libre (0.03%-10%)
How do liposoluble hormone receptors work?
Cellular response caused by an intracellular receptor
What are the two kinds:
- Cytoplasmic (steroids)
- Nuclear (type stéroïdes): TR, ER, VDR, RXR
How do steroid hormone receptors work?
What are the three parts of nuclear receptors?
- Ligand binding domain: on receptor binds to hormone
- DNA binding domain: binds to nuclear DNA which activated protein synthesis
- N-terminal domain: modulate hormonal activity
How do “type stéroïde” receptors work?
What happens when intracellular receptors are activated?
- Start or stop the activity of specific genes
- Start or stop the synthesis of specific enzymes
- Provoque physiological reactions specific to the target call
What are the characteristics of peptidic and steroid hormones?
Peptidique:
- Hydrosoluble
- Non liées
- Courte demi-vie
- Récepteurs membranaires (G-protein, tyrosine kinase)
Stéroides:
- Liposoluble
- Liées à des protéines de transport
- Demi-vie + longue
- Récepteurs intracellulaires (cytoplasmique, nucléaire)
What are hormone secretion and action controlled by? (6)
- SNC
- Immune system
- Age
- Pregnancy
- Circadian cycle/rhythm
- Negative and positive feedback
What do hypo and hyper mean?
Hypo: diminution sécrétion hormonale (glande cible)
Hyper: augmentation sécrétion hormonale (glande cible)
What are the three main mechanisms that cause endocrinopathies?
- Déficience hormonale
- Excès de sécrétion hormonale
- Résistance hormonale
How do hormonal deficiencies work?
Destruction of glandular tissue:
- dim. hormonale secretion
- lower hormonal concentration
- dim. hormonal action in the tissue –> hypo
Causes:
- Infection (ex: tuberculosis)
- Autoimmune (ex: cytotoxicity, blockers)
- Vascular (ex: Sheehan)
- Inflammation
- Tumours (ex: craniopharyngoma)
- Hereditary (ex: athyeosis)
- Chx, radiotx, chimiotx
How does excessive hormone secretion happen?
Causes:
- increased hormone secretion
- increased plasmatic concentration of homrones
- increased action of glandular tissue –> hyper
How?
- Increased production due to loss of sensibility to retroaction systems
- Malignant tissue that produces hormones
- Peripheral transformation of precursors into hormones by other tissues
- Cellular destruction causes hormones to be released
- Autoimmunity
- Iatrogenic
Causes of hormonal resistance:
- Acquired/congenital (mutations)
- Heterogenic mutations
These mutations can prevent:
- Hormone binding to receptor
- Receptor binding to hormone
- Hormone working after binding to receptor
Presentation?
- Normal or increased hormone levels with sx of hormonal deficiency
- ex: complete androgen insensitivity syndrome and insulin resistance
How can endocrine function be evaluated?
- Hormonal dosage
- If you think its hyposecretion –> stimulation tests
- If you think its hypersecretion –> suppression tests
- Imagery (only done once you know what the problem is)
- Look at glandular anatomy
- Look for tumours/nodes
What kinds of imagery can be used to evaluate different glands?
- Echo: thyroid, ovaries, testicles
- TDM: selle turcique (pituitary), adrenals, pancreas
- MRI: more sensible than TDM but same organs
- Nuclear medicine:
- Sestamibi/Tech: parathyroid adenoma
- Iodine (capture/scintigraphie): functional nodules, hyperthyroidism
