Introduction To Endocrinology Flashcards
Define endocrinology.
The study of endocrine glands (tissues) + the substances they secrete
Define endocrine gland.
A gland that makes + secretes hormones into the bloodstream through which they travel to affect distant targets
Define hormone.
A chemical substance produced by cells + released especially into the blood + having a specific effect on cells or organs usually at a distance from the place of origin
Define exocrine gland.
A gland that secretes its products through ducts opening onto an epithelium rather than directly into the blood
What is endocrine secretion?
Secretion of a hormone into the blood stream to act on a distal tissue
What is the definition of endocrine?
Of, relating to, promoted by, or being a substance (hormone) secreted be cells of a gland into the bloodstream through which is travels to act on distant targets
What is the definition of paracrine?
Of, relating to, promoted by, or being a substance secreted by a cell + acting on adjacent cells
What is the definition of autocrine?
Of, relating to, promoted by, or being a substance secreted by a cell + acting on surface receptors of the same cell
What type of chemical messengers exist?
Neurotransmitters
Neuroendocrine hormones
Endocrine hormones
Cytokines (peptides with autocrine, paracrine + endocrine functions)
Give a brief overview of the endocrine system.
- The endocrine system receives chemical + physical stimuli
- It responds by releasing a chemical signal e.g. hormone
- The signal will elicit a change in the tissue e.g. change in metabolic rate or increased secretion
What are the main endocrine organs?
Hypothalamus Pituitary Thyroid Thymus Adrenal Pancreas Kidney Ovary Uterus Testes
What tissues have an endocrine function?
Heart Gut Liver Adipocytes Placenta
What are the main molecular types of hormones?
Polypeptides
Modified AAs
Steroids
Gives some examples of hormones derived from amino acids.
- Single AAs e.g. catecholamines + 5-HT
- Dipeptides e.g. thyroid hormones
- Small peptides e.g. TRH, vasopressin + somatostatin
- Intermediate size e.g. insulin, PTH
- Complex polypeptides e.g. gonadotrophs (FSH, TSH + LH)
Gives some examples of hormones derived from lipid precursors.
- Cholesterol e.g. steroids (Cortisol, sex steroids + vitamin D)
- FAs e.g. prostaglandins
What are the characteristics of peptide and catecholamine hormones?
Rapid changes in [plasma]
Short (sec-min) T/12
Cell membrane receptor
Activate preformed enzymes, secretory granules, constitutive + burst
Rapid (sec-min) affect
What are the characteristics of steroid and thyroid hormones?
Slow fluctuations in [plasma]
Long (min-days) T1/2
IC receptor
Stimulate protein synthesis, direct rapid passage, related to secretion rate
Slow (hrs-days) affect
How are protein and peptide hormones synthesized and secreted?
- Gene transcription in nucleus
- mRNA goes to RER
- Translated on RER
- Post-translational processing in golgi
- Packaging into secretory vesicles
- Exocytosis
How are steroid hormones synthesized and secreted?
- Hydrolysis of esters + release of cholesterol (or cholesterol uptake)
- Cholesterol converted to pregnenolone in mitochondrion
- Processing in SER
- Diffusion out of cell
What occurs in post-translational processing of Parathyroid Hormone (PTH)?
- Initially synthesized as long polypeptide pre-Pro-PTH (115 residues)
- Enters ER + cleaved to form pro-PTH (90 residues)
- Cleaved further in vesicle secretions
- PTH (84 residues) is secreted
What is special about steroid hormone synthesis?
No gene activation; enzymatic processing
Not stored but processed when required
Type + activity of enzymes (tissue specific) determines type + amount of hormones (e.g. deiodinases + adrenal/gonads)
What are the ways in which hormones can be transported in the blood?
- Water soluble hormones dissolve in blood
2. Hydrophobic/fat-soluble hormones (steroid + thyroid hormones) are transported bound to plasma binding proteins
What is important when considering hormone transport by plasma protein binding?
Binding affinity
Bound hormone is considered to be inactive, protected from degradation + acts as a reservoir
Where do water soluble hormones bind to exert their effect?
Cannot pass through membranes so bind to cell surface receptors e.g. GPCR, TKR
What can happen when a hormone binds to a G-Protein Coupled Receptor (GPCR)?
Stimulatory or inhibitory effects on 1 of 2 pathways:
- G proteins -> adenylate cyclase -> cAMP -> protein kinases
- G proteins -> PLC -> IP3 -> Ca2+ released from ER
What happens when a hormone binds to a Tyrosine Kinase Receptor (TKR)? What hormone binds to these?
Phosphorylation of receptor -> signalling cascades
E.G. insulin
Where do hydrophobic hormones bind to exert their effect?
Bind to IC + cell surface receptors
Explain steroid hormone receptor signalling briefly.
Protein carrier brings steroid hormone to cell surface receptor (rapid response)
OR
Steroid hormone is brought directly into the cell to bind a cytoplasmic receptor which moves into the nucleus activating transcription, translation + production of new proteins
Explain the feedback axes of the most basic kind of endocrine gland.
- Gland receives chemical signal (trophic hormone) from another gland to increase or inhibit secretion
- Gland will secrete effector hormone
- Increased levels of effector hormone will cause:
- Response in target cells
- Inhibition of further trophic hormone secretion
What is the difference between a tropic and trophic hormone?
Tropic hormones affect other endocrine glands whereas trophic hormones affect growth + development directly
Describe the general endocrine feedback system of the HPA axis.
Hypothalamus -> releasing hormone -> anterior pituitary -> tropic hormone -> target endocrine gland -> hormone feedbacks to anterior pituitary + hypothalamus
What are some examples of releasing and tropic hormones?
CRH -> ACTH LHRH -> LH, FSH TRH -> TSH PIH/GHRH -> PRL GHRH/GHIH -> GH
Briefly explain the concept of negative feedback.
Increased output from target cells or increased hormone will negatively feedback on trophic + tropic hormones inhibiting its further release
Briefly explain the concept of positive feedback.
Increased levels of effector hormone cause increased levels of tropic + trophic hormone
What is the main positive feedback example?
Oestrogen causing LH surge
What is the difference between primary and secondary endocrine dysfunction?
Primary dysfunction is too much of effector hormone from endocrine organ whereas secondary dysfunction is overstimulation of the effector organ by excessive tropic hormone
What can cause excessive hormone (hyper) production?
Neoplasm
Hyperplasia
Ectopic production
What can cause too little hormone (hypo) production?
Gland destruction (trauma, disease, autoimmune) Not developed
What can cause a failure to respond to a hormone (resistance)?
Receptor problems
IC signalling defects
What effects does the glucocorticoid cortisol have?
Maintain muscle function + decrease muscle mass
Decrease bone function + increase bone resorption
Decreased connective tissue
Inhibit inflammatory + immune response
Maintain CO: decrease endothelial permeability + increased arteriolar tone
Facilitate maturation of foetus
Increased glomerular filtration + H2O clearance
Modulate emotional tone + wakefulness
What is the disease caused by glucocorticoid excess? What are its symptoms?
Cushings syndrome
Symptoms: Central weight gain but loss of musculature in extremities Change in appearance (moon face) Depression Psychosis Insomnia Amenorrhoea Poor libido Thin skin Bruising Growth arrest Back pain Polyuria/polydipsia
What is the treatment for excess glucocorticoid?
Reduce cortisol via surgery to remove tumour or drugs to inhibit cortisol production
What is the disease caused by reduced glucocorticoids/mineralocorticoids? What are its symptoms?
Hypoadrenalism/Addison’s
Symptoms: Weight loss Anorexia Weakness Fever Depression Impotence/amenorrhoea Nausea/vomiting Diarrhoea/constipation Confusion Abdominal pain Back pain
What are the causes of reduced glucocorticoids/mineralocorticoids?
Destruction of adrenal cortex
Reduced glucocorticoid, mineralocorticoid + sex steroid production
Describe the feedback loop of thyroid hormones.
- Hypothalamus secretes TRH
- TRH acts on anterior pituitary
- Anterior pituitary releases TSH
- TSH acts on thyroid gland to affect thyroid hormone synthesis + release
- Thyroid hormones can inhibit the hypothalamus + anterior pituitary
What is meant by ‘free’ thyroid hormones?
T3/T4 are carried in the blood bound to albumin + TBG
Only a small amount of T3/T4 are unbound + free to have a biological effect on tissues - these are free hormones
Describe the HPA axis feedback loop of cortisol.
- Hypothalamus produces CRH
- CRH acts on anterior pituitary
- Anterior pituitary produces ACTH
- ACTH acts on adrenal gland
- Cortisol is produced which can inhibit the anterior pituitary + hypothalamus
What can cause an glucocorticoid excess?
Pituitary gland tumour
Ectopic ACTH syndrome (ACTH produced from a tumour in the lung, pancreas, thyroid or thymus gland)
Adrenal gland abnormality/tumour
Long-term use of corticosteroid medication
Familial
