Endocrinology Flashcards
Describe the endocrine response
Hormone released and has an effect on distant target cells
Describe the paracrine response
Hormone released and acts on adjacent cells
Describe the autocrine response
Hormone released and hits target cells but loops back to the secretory cells and binds to targets there
Give examples protein hormones
Oxytocin ADH Growth hormone (somatotropin) Prolactin FSH and TSH Insulin
Where are oxytocin and ADH produced?
Posterior pituitary
How do oxytocin and ADH differ?
Their amino acid sequence differ at 2 positions
Describe the functions of growth hormone
Stimulate growth, cell division and regeneration.
It is a mitogen (stimulates mitosis) and is specific to only certain kinds of cells
Describe the characteristics of prolactin
198 protein residue closely related to GH and Placental lactose with properties resembling a hormone and cytokine
Where are FSH and TH produced?
Anterior pituitary
What is the major drug delivery issue for peptide and protein pharmaceuticals?
Proteins get digested
Which hormones are derived from tyrosine?
Dopamine Noradrenaline Adrenaline T3 T4
Which hormones are derived from tryptophan?
Melatonin
- derived from dietary tryptophan via serotonin
Give examples of steroid hormones
Progesterone
Testosterone
Oestradiol
Cortisol
What is structurally similar in steroid hormones?
All have the same basic C17, 4 ring structure
What are the 2 kinds of endocrine organs? What are their functions?
Primary: function is the secretion of hormones
Secondary: non-endocrine primary function
Where are the hypothalamus, pituitary and pineal glands located?
Hypothalamus: below the thalamus above the brain stem
Pituitary gland: sits in a small bone cavity below the hypothalamus
Pineal gland: epithalamus, between 2 hemispheres in the centre of the brain
What kind of hormones do the hypothalamus and pituitary produce?
Regulatory hormones which control the function of other endocrine glands
Which hormone does the pineal gland produce?
Melatonin - helps to regulate the circadian rhythm
Where are the thyroid and parathyroid glands located?
In the neck region just below the larynx, sits about and around the trachea
Which hormones do the thyroid glands produce?
T3 and T4 - they help to regulate metabolism
Calcitonin
Which hormone does the parathyroid gland produce? When are hormones released?
Parathyroid hormone
They release hormones when the biological signal goes down [Ca] needs to drop for the hormone to be released.
Where is the thymus located?
Close to the heart
Which hormone does the thymus produce and what is its function?
Thymosin
Stimulates the activity of T cells and antibody production in the bone marrow
Why is the thymus critical for immune response?
T cells mature in the thymus
Which hormones do the islets of Langerhans produce?
Insulin Glucagon Somatostatin (GH) Ghrelin Pancreatic polypeptide
Define hyposecretion in terms of endocrine disorders
A gland doesn’t produce enough of its hormones
Define hypersecretion in terms of endocrine disorders
A gland produces too much of its hormones
Give examples of diseases caused by hypersecretion of hormones
Hyperinsulinsim
Cushing’s
Grave’s disease
Give examples of diseases caused by hyposecretion of hormones
Diabetes
Hypothyroidism
Addision’s disease
Give examples of tumours that may develop in the endocrine glands
Multiple endocrine neoplasia
Pheochromocytoma - too much adrenaline in the blood
Where are the adrenal glands located and what are responsible for releasing?
There are 2 at the top of the kidney
Release hormones in response to stress
What are the 2 distinct regions of the adrenal glands?
Central medulla
Outer cortex
What kind of effect does cortisol have on steroid synthesis?
Negative effect
Which part of the brain is responsible for detection of stressful situations?
Hypothalamus
What happens when cortisol is released in the HPA axis?
It inhibits the anterior pituitary to inhibit further release of ACTH and also inhibits further release of CRH from the hypothalamus
Which hormones do the ovaries secrete?
Steroids: oestrogen and progesterone
Protein hormones: inhibit and relaxin
Which hormones regulate the secretion of ovarian hormones?
FSH and LH
Which hormones do the testes produce?
Steroid: androgens and testosterone
Describe the function of the placenta
Links a developing foetus to the maternal uterine wall. It facilitates nutrient uptake, removal of waste products and gas exchange through the maternal blood supply
Which hormones does the placenta produce?
Steroid: oestrogen and progesterone
Protein: hCG, CRH, placental lactogenic
Describe the function of the atrial natriuretic peptide (ANP)
Stimulates the kidney to secrete more salt, this decreases excess blood volume, high BP and high blood sodium concentration
What is the approximate number of hormones in the GI tract?
30
Which hormones do juxtaglomerular cells secrete? And what is the function of these hormones?
Renin - signals adrenal cortex to secrete aldosteron
Erythropoietin - signals bone marrow to increase RBC production
Describe the function of parvicellular neurons in the hypothalamus
Secrete regulatory hormones into the bloodstrream which travel through the portal system to the anterior pituitary lobe - this triggers the secretion of other hormones
How does the hypothalamus control the anterior pituitary?
By secreting regulatory hormones
What is TRH and what is its function?
Thryotropin releasing hormone
It has a positive tropic effect on TSH from the anterior pituitary, and it acts on the thyroid gland to increase section of thyroid hormones
What is CRH and what is its function?
Corticotropin releasing hormone
Positive effect on anterior to increase production of ACTH which exerts effect on the adrenal cortex of the kidney to increase production of steroid hormones
What is GHRH and what is its function?
Growth hormone releasing hormone
Positive tropic effect, increased production of growth hormone. GH has an effect on growth of many tissues in the body and also influences secretion of insulin growth factors
What is GHIH and what is its function?
Growth hormone inhibiting hormone
Has a negative tropic effect. Helps to regulate GH secretion by reducing GH secretion
What is GnRH and what is its function?
Gonadotropin releasing hormone
Has a positive tropic effect on cells to increase secretion of Fish and LH which have a physiological effect on gonads for the production of sex hormones
Define topic in terms of hormones
Act on another endocrine gland to produce effector hormones
Define non-tropic in terms of hormones
Doesn’t involved another endocrine gland - they act directly on other tissues
Give examples of tropic hormones
FSH and LH
ACTH - adrenocorticotropic hormone (corticotropin)
TSH - thyroid stimulating hormone (thyrotropin)
Describe the function of TSH
Synthesised, stored and secreted from thryrotopes
Stimulates thyroid gland to produce thyroid hormones
Describe the function of ACTH
Synthesised, stored and secreted from corticotropes
Stimulates the adrenal gland cortex to produce corticosteroids such as aldosterone and cortisol
Give examples of non-tropic hormones
Prolactin
Growth hormone
Describe the structure and function of prolactin
198 AA single chain polypeptide
Synthesised, stored and secreted by lactoptropes
Exerts effects on breast tissue for lactation
Dysregulation causes issues
What is the post common tumour of the pituitary? How is it treated?
Prolactinoma
Treated with dopamine and receptor agonists
- Bromocriptine and cabergoline
Describe the structure and function of growth hormone
191 AA single chain polypeptide
Synthesised, stored and secreted by somatropes
Stimulates growth, cell reproduction and regeneration of specific cells
What does hypersecretion of growth hormone cause?
Gigantism in children and acromegaly in adults
How is acromegaly treated?
Somatostatin
Regulates the production of GH and affects cell proliferation and growth via somatostatin receptors
Which hormones are secreted by the posterior pituitary gland?
Oxytocin
Vasopressin (ADH)
Describe the function of oxytocin
Stimulation of milk ejection
Stimulation of uterine smooth muscle contraction at birth
During child birth, baby presses down on cervix, pressure activates sensory nerves which causes a reflex arch back up to hypothalamus, oxytocin is released in waves as a result of the feedback, as it diffuses down to uterus and binds to receptors on uterine muscle it causes contraction - pushing baby’s head down further and stimulate sensory nerves more, this cycle continues until baby is pushed out.
What is pitocin used for? What needs to be monitored when its used?
Used to advance child birth
Need to monitor maternal BP, pulse changes and hypertonicity of the uterus
Need to monitor FHR and rhythm
Describe the function of vasopressin
Binds to V2 receptors on cells in the collecting ducts and on the distal convoluted tubule of the kidney
ontrols synthesis of aquaporins (2) which is inserted on the apical membrane of kidney cells - allows water to be reabsorbed from the kidney tubule.
What happens in the absence of vasopressin?
The collecting ducts are impermeable to water, this flows out as urine
What is diabetes insipidus?
Excessive urine production
Which cells secrete melatonin?
Pinealocytes
How is production of melatonin controlled?
Production is permitted by darkness and inhibited by light
Where are the adrenal glands located?
On top of the kidneys
What are the different parts of the adrenal glands?
Capsule
Cortex
Adrenal medulla
What are the 3 different zones in the cortex and what is produced there?
Zona glomerulosa: mineralcorticoids e.g. aldosterone
Zona fasciculata: glucocorticoids e.g. cortisol
Zona reticularis: androgens
Are steroids stored?
No - they are synthesised from cholesterol on demand
What are the physiological functions of adrenal steroids?
Glucocorticoids: metabolic effects, anti-inflammatory, immunosuppressive
Mineralcorticoids: water and electrolyte balance
Adrenal androgens: maturation and development
Describe the mechanism of action of corticosteroids
Corticosteroid binding globulin bind 90% of cortisol and 60% of aldosterone
Transcortin doesn’t bind synthetic steroids
Steroids are carried by carrier proteins in the body. Steroids interact with receptors on the cell membrane and are picked up by cytoplasmic receptors inside
Interact with the nucleus where they initiate gene transcription and translation.
Steroids take time to act as they need new proteins to be made from cells
Describe the mechanism of action of mineralcorticoids
MC receptors have limited tissue distribution
MCs cause Na+ uptake which leads to fluid resorption and K+ loss.
ATII releases aldosterone from the adrenal cortex, this works on the kidneys and allows reabsorption of Na+ so that water can enter by osmosis
What properties to synthetic steroids have?
Varying durations of actions
Different split of activities and potencies
What are the different durations of actions that synthetic steroids can have?
Short acting: T1/2 = 8-12hours
Intermediate: T1/2 = 12-36hours
Long acting: T1/2 = 36-72hours
What are the different combinations of synthetic steroids? Give examples
Mixed glucocorticoid and mineralocorticoid activity
- prednisolone
Pure glucocorticoid
- dexamethasone, betaethasone, beclometasone
Mainly mineralocorticoid
- fludrocortisone
How are steroids used in replacement therapy in adrenal failure?
Addisions Disease
- hydrocortisone (GC) with or without fludrocortisone
Congenital adrenal hyperplasia
- dexamethasone, betamethasone
Describe congenital adrenal hyperplasia
There is a fault in steroidogensis pathway, overproduction of androgens, limited / no cortisol negative feedback and ACTH output is raised.
How are steroid used as anti-inflammatory’s and immunosuppressants?
They reduce mediators of inflammation and immune responses including prostaglandin cytokines, NO, IgG
Which steroids are used as anti-inflammatory’s and immunosuppressants?
Hydrocortiosone Prednisolone Beclomethasone Dexamethasone Budesonide
What are the side effects and problems of steroid use?
Excessive use of GC leads to inappropriate metabolic effects on the body
- Drug induced Cushing’s syndrome
- Oesteoporosis
Increased risk of infection
Which drugs are used to target steroidogenesis?
Aminoglutethimide
Metrypone
Tetracostide
Describe the MoA of aminoglutethimide and give its uses
Inhibits enzymes and reduces steroid output
Uses: Cushing’s, postmenopausal breast cancer and prostate cancer
Describe the MoA of metryapone and give its uses
Inhibits 11 beta-hydroxylase and reduces GC, MC synthesis
Uses: Cushing’s and hyperaldosteronism
Describe the MoA of tetracostide and give its uses
Stimulates synthesis and release of adrenal hormones
Used to diagnose adrenal cortical insufficiency
