Endocrinology Flashcards
Define:
Endocrine
Autocrine
Paracrine
- Endocrine – act on remote tissue
- Autocrine – chemical mediator acts on its own producers
- Paracrine – mediators act on adjacent cells
State the functions of hormones.
Homeostatic mechanism
Energy production, utilisation and storage
Growth and development
Reproduction
Name the classifications of hormones. With examples for extra points
Peptides – oxytocin, ACTH, insulin, prolactin
Glycoproteins -LH, FSH, TSH
Amino – dervide – thyroid hormones
Steroids – cortisol, testosterone, vitamin D
Catechol – adrenaline and noradrenaline
Others – fatty acid based hormones
What is the general mechanism of hormones to elicit a change?
Trigger change in cellular activity or genetic regulation. Requires the activation of intracellular systems to be activated, e.g. cAMP
What is the major differences between steroid hormones and proteins and amines?
Proteins and amines bind to cell surface receptors to trigger intracellular secondary messengers, whilst steroid hormones can diffuse directly into cells and bind intracellular receptors. The steroid-receptor complex moves into the nucleus to activate or suppress specific genes
Protein hormones act very quickly (30s-2min), but have shorter effects compared to steroid hormones which produce a longer lasting effect (takes longer for onset)
What are the major hormone pathways? And by what system are they modulated?
Hypothalamus – pituatary – adrenal axis
Hypothalamus – pituatary – gonadal axis
Hypothalamus – pituatary – thyroid axis
ADH-water balance
Modulation occurs via an organised hierachiral loop that allow feed forward and feedback to regulate response
How are the different parts of the pituitary gland stimulated?
They are stimulated by the hypothalamus (key area involved in metabolic and homeostatic processes).
Anterior pituitary is stimulated by using peptides carried by capillaries
Posterior is stimulated by using neuronal signals
What hormones are produced by what part of the pituitary gland?
Anterior
- Adrenocorticotrophic hormone (ACTH); multiple effects
- Growth hormone (GH)
- Follicle stimulating hormone (FSH)
- Luteinising hormone (LH)
- Prolactin
- Thyroid stimulating hormone: metabolism
Prolactin, LH and FSH are all related to reproduction
Posterior
- Antidiuretic hormone
- AKA arganine vasopressin
- Oxytocin
Look at the HP-adrenal axis and describe the mechanism of the hormonal release and the modulation of the response.
Cortisol is a key stress response steroid hormone
- Stimulates glucose production
- Fight or flight mechanism – maintain glucose levels
Stimulates glucose production and modulates the immune response
Stress (any stress, psycholoigcal or physical) induced CRH released from the HypoT
- In turn stimulatles ACTH from the pituitary gland and cortisol from adrenal gland
- Cortisol induces own negative feedback
Look at the HP-Gonadal axis (male) and describe the mechanism of the hormonal release and the modulation of the response.
At the hypothalamus level there is the gonadotrophin releasing hormone (GnRH)
The release of GnRH stimulates both LH and FSH in the anterior pituitary
Both act on cells found in the testis
- LH act on leydig cells via testosterone release
- FSH stimulates spermatogenesis in sertoli cells
Negative feedback loop exists where the testosterone is able to inhibit the function of GnRH to stimulate the anterior pituitary gland
Look at the HP-Gonadal axis (female) and describe the mechanism of the hormonal release and the modulation of the response.
In females it is similar to males as the release in of GnRH in the hypothalamus kickstarts the axis
The release of GnRH stimulates both LH and FSH in the anterior pituitary
The action of LH and FSH in females are slightly different than males, but not completely foreign – mainly in that it acts in the ovary
- LH act to stimulate progesterone (in corpus luteum) as well as estrogen (in the ovary) release in the ovaries
- FSH stimulates the release of estrogen in the ovary
- Estrogen functions to trigger ovulation
Negative and positive feedback loops are present in the HP gonadal axis
- This is mediated by two seperate hormones
- Estrogen
- Can both positively or negatively affect the FSH or even inhibit GnRH action – depending on where in the menstrual cycle they are
- Progesterone
- Only feedsback to GnRH in a negative way – to inhibit its functions
Look at the HP-thyroid axis and describe the mechanism of the hormonal release and the modulation of the response.
- Thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) are key regulators of metabolic rate
- TRH (thyroid releasing hormone) released from the hypothalamus
- Stimulates TSH
- In turn stimulates thyroid hormone synthesis and release from the thyroid gland
- Neg feedback loop by the T3, which can inhibit the function of TSH and TRH
Look at the HP-ADH axis and describe the mechanism of the hormonal release and the modulation of the response.
- Major axis regulating circulatory volume
- HypoT stimulates ADH release from post pit via neuronal connection
- ADH stimulates H20 reabsorption in the kidney
- Falling plasma osmo will decrease ADH release
- Parallel thirst pathway
- But, pathway can be overriden by other stimuli leading to XS ADH release
- In increases of plasma osmolality – increased solutes in the blood
o This indicates to the body there is not enough water to go around
o This will manifest itself as thirst to bring about an increase in water intake – which in return lowers the plasma osmolality by rehydrating the cells
o However, this is not enough as the body needs to reabosrb the increased water intake
o This occurs by the hypothalamus neuronal stimulation of ADH at the posterior pituitary
-> ADH act in the kidney to increase water reabsorption and decrease urine volume – decreased urine volume decreases plasma osmolality
What physiological factors are associated with hormone production?
Time of day, Time of month, time of year, age, sex, stress, diet, illness, drugs
What are some common measurements of hormone levels?
Immunoassay, chemical detection (HPLC-UV, Mass spec)
What must be considered when measuring hormone levels?
There may be interferance/mis-reading, in commercial assays, since many steroid hormones exist with similar chemical structures.
A scientist need to consider whether the correct form is being measured, as hormones exist in both bound and unbound forms. Typically the unbound form is biologically active, but difficult to measure. e.g. T4 vs T3
Is it the correct sample type?
Results may be skewed due to treatment, as some medicine use the same or similar hormone to that produced endogenously, e.g. thyroid medication is the same as endogenous T4
or
Commonly used steroids are derivatives of cortisol, which will give false raises in cortisol.
In the determination and assessment of a patient endocrinological status, is a singular hormone level enough to diagnose the patient?
NO, a singular hormone does not tell the whole picture, but rather a small part of the it. The whole axis needs to be considered before a it can be used as a diagnostic
What tests can be administered to investigate hormone excess and deficient state?
Suppression test. E.g. give dexamethasone in a deaxemethasone suppression test. Suppress the hypothalamus ability by working similarly to cortisol. The test should result in a decreased concentration of cortisol.
Stimulating test. Give synachten (ACTH) in short synacthen test. ACTH stimulates the production. Useful in investigating low cortisol, as seen in addisons.
Discuss some specific sample types for correct measurement of hormones
Serum - whole blood, which naturally clots. Seperate clot, RBC and the different cells. What is left is serum. Sometimes we don´t want it to clot so we use tubes coated with lithium heparin (ACTH, insulin or aldosterone) or EDTA (gut hormones).
Plasma is inhibiting the clotting and then seperating the blood.
Urine - in 24hr urine collections can show the free cortisol present in the body, metadrenalines or 5-HIAA
What hormone type effect occurs rapidly? and why?
The protein hormones bind to cell surface receptors and can act within 30s-2min with shorter effects.
Steroid hormones, due to being lipid soluble can diffues directly into the cell and bind intracellular receptors to trigger or suppress specific genes. Can take hours to alter genetic activity, but produce a long lasting effect
Why can steroid hormones diffuse directly into the cells?
A. Non-polar
B. Polar
C. Lipid soluble
D. Water soluble
C.
What describes protein hormones the best? pick more than one
A. Has a long lasting effect B. Act via cell surface receptors C. Has shorter effects D. Act very quickly 30s-2min E. Can directly diffuse into the cells
BCD
What is self limiting within an endocrine pathway? and why might it be useful? Pick two.
A. Its a pathway to minimise ATP loss
B. Operates to regulate the response
C. The incorporation of positive feedback loop
D. The incorporation of negative feedback loop
E. Operates to enhance the response to a secreted hormone
B, D
Draw an example of how an endocrine reponse may be modulated.
Show a negative feedback loop
What is central to most endocrine pathways?
A. Response to PAMP and DAMP
B. Nervous system
C. Electrolyte balance
D. Hypothalamus
D
How does the hypothalamus stimulate the anterior pituitary?
Occurs using peptides carried by portal capillaries
How does the hypothalamus stimulate the posterior pituitary?
Using neuronal signals in the pituitary stalk - direct connection here
What hormones below are produced by the anterior pituitrary gland?
A. ACTH B. LH C. Oxyctocin D. AVP E. FSH F. Prolactin G.GH H. ADH I. TSH
All except - C, D, H
What hormones below are produced by the posterior pituitrary gland?
A. ACTH B. LH C. Oxyctocin D. AVP E. FSH F. Prolactin G.GH H. ADH I. TSH
CDH
Match hormones with functions.
A. ACTH
B. FSH, LH, Prolactin
C. ADH, AVP
D. TSH
- Water balance
- Multiple effects
- Metabolism
- Reproduction
A2
B4
C1
D3
In simple terms how does the HP-adrenal axis work?
This axis is uses cortisol (steroid hormone) as a stress response. The cortisol acts to stimulate glucose production and modulation of the immune system.
The hypothalamus will secrete CRH upon stress, which act on the anterior pituitary (via portal capillary) to synthesis and secrete ACTH. ACTH acts on the adrenal glands to release cortisol to induce glucose production.
Describe the HP adrenal modulation.
Modulation occurs by cortisol (when there is too much) negative feedback on both ACTH and CRH.
Counteracts possible formation of hyperglycaemia - seen in Cushings syndrome (prolonged exposure of cortisol)
In simple terms how does the HP-gonadla axis (male) work?
Gonadotrophin releasing hormone (GnRH) is synthesised by the hypoT. GnRH can stimulate the synthesis of both LH and FSH in the anterior pituitary. LH act on leydig cells to produce testosterone, whilst FSH act on sertoli cells for spermatogenesis (both occur in testis).
Modulation of the HP-gonadal axis (male).
Modulated by a negative feedback loop of testosterone on the GnRH production.
In simple terms how does the HP-gonadal axis (female) work?
Similar to male in that it also begins with GnRH synthesis at the HypoT, which act on LH and FSH in the anterior pituitary. The targets of LH and FSH are different to male, progesterone (corpus luteum) and estrogen (ovary) respectively (LH and FSH act on ovary). Estrogen is involved in ovulation.
Modulation of the HP-gonadal axis (female).
Both estrogen and progesterone can negatively feedback to GnRH synthesis to regulate the axis. Here however, estrogen can also negatively or postively stimulate FSH, which is depdent on menstrual cycle
In simple terms how does the HP-thyroid axis work?
Thyroid gland plays a major role in metabolism (bone), growth and development of the human body.
Begins with secretion of thyroid releasing hormone (e.g. response to low calcium) which induces secretion of TSH in the anterior pituitary. TSH act on the thyroid to produce thyroxine (T4) or triiodothyronine(T3). T4 can be converted into T3 in peripheral tissues, because T3 is biologically active.
Modulation of the HP-thyroid axis .
Negative feedback loop of T3 on TRH synthesis
What is the purpose of T4->T3 in peripheral tissue following secretion by pituitary?
A. Formation of biologically active unit
B. Biologically active -> inactive
C. Result of being used in a chemical reaction
D. One T has been released
A
In simple terms how does the HP-ADH axis work?
Important axis in the reabsorption of water at the collecting ducts.
Here the HypoT act on the posterior pituitary via the neural link to release ADH following increased plasma osmolality. The ADH act on the kidneys collecting ducts to reabsorb water from the filtrate.
Modulation of HP-ADH axis
If water intake increases the plasma osmolality is stabilised and does not increase. negative
Decrease in urine volume negatively feedbacks to plasma osmolality increase.
When investigating disease linked to abnormal hormone levels, what needs to be taken into account?
A. Height B. Diet C. Ilness D.Drugs E. Time of day F. Sex G. Stress H. Age I. Time of month J. Time of year
All except A
Examples. Time of day - cortisol Time of month - estrogen Time of year - TSH Stress - cortisol Sex - gonadal Dugs - may impact hormonal control Age - testosterone decrease with age
Describe immunoassays.
Uses labelled antibody designed to specifically recognise a specfic region present on the target protein or molecule - often only feasible if there is a unique antigen epitope
What is appropriate for investigating hormone excess or deficient states? pick more than 1
A. Hypofunction -> suppression test
B. Hyperfunction -> suppression test
C. Both suppression and stimulation are approporiate for hypo
D. Hypofunction -> stimulation test
E. Both suppression and stimulation are approporiate for hyper
F. Hyperfunction -> stimulation test
D, B
What describes Cushing syndrome the best and how it will be appropriately investigated?
A. Hyperfunctional HypoT -> short synachten test
B. Hypofunctional ->Dexamethasone suppression test
C. Measurement of ACTH levels
D. Hypofunctional HypoT -> Short synachten test
E. Hyperfunctional -> Dexamethasone suppression test
E
What describes Addisons disease the best and how it will be appropriately investigated?
A. Hyperfunctional HypoT -> short synachten test
B. Hypofunctional ->Dexamethasone suppression test
C. Measurement of ACTH levels
D. Hypofunctional HypoT -> Short synachten test
E. Hyperfunctional -> Dexamethasone suppression test
D
Why perform a stimulation or suppression test?
- Low hormone levels are not diagnostic
- Normal hormone levels do not exlude disease, compensation
- Pulsatile secretion and diurinal variations confuse interpretation of baseline values
- Can aid in differential diagnosis in hormone excess states
What is addisons and how is it investigated?
Hypofunction of adrenal gland resulting in low cortisol levels
- Investigated using short synacthen test to stimulate adrenal gland using ACTH
What is cushings and how is it investigated?
Hyperfunction of the hypothalamus releasing CRH resulting in chronic hyperglycaemia.
- Investigated using a dexamethasone suppression test using cortisol analogue as an inhibitor
