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