Introduction To Endocrinology Flashcards by frankiespeck@hotmail.co.uk Speck

Define endocrinology.

The study of endocrine glands (tissues) + the substances they secrete

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Define endocrine gland.

A gland that makes + secretes hormones into the bloodstream through which they travel to affect distant targets

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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

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Define exocrine gland.

A gland that secretes its products through ducts opening onto an epithelium rather than directly into the blood

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What is endocrine secretion?

Secretion of a hormone into the blood stream to act on a distal tissue

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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

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What is the definition of paracrine?

Of, relating to, promoted by, or being a substance secreted by a cell + acting on adjacent cells

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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

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What type of chemical messengers exist?

Neurotransmitters
Neuroendocrine hormones
Endocrine hormones
Cytokines (peptides with autocrine, paracrine + endocrine functions)

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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

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What are the main endocrine organs?

Hypothalamus
Pituitary 
Thyroid
Thymus
Adrenal
Pancreas 
Kidney 
Ovary 
Uterus
Testes

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What tissues have an endocrine function?

Heart
Gut
Liver 
Adipocytes
Placenta

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What are the main molecular types of hormones?

Polypeptides
Modified AAs
Steroids

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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)

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Gives some examples of hormones derived from lipid precursors.

Cholesterol e.g. steroids (Cortisol, sex steroids + vitamin D)
FAs e.g. prostaglandins

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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

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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

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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

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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

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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.

1. Gland receives chemical signal (trophic hormone) from another gland to increase or inhibit secretion 2. Gland will secrete effector hormone 3. 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.

1. Hypothalamus secretes TRH 2. TRH acts on anterior pituitary 3. Anterior pituitary releases TSH 4. TSH acts on thyroid gland to affect thyroid hormone synthesis + release 5. 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.

1. Hypothalamus produces CRH 2. CRH acts on anterior pituitary 3. Anterior pituitary produces ACTH 4. ACTH acts on adrenal gland 5. 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