human development - endocrinology Flashcards
what are the two types of glands?
- endocrine (inside the body)
- exocrine (outside the body)
what is the difference between endocrine and exocrine glands?
- endocrine glands are directly released into circulation
- exocrine glands are released outside of the body, via a duct
what is a hormone?
- a chemical substance
- secreted without the benefit of a duct
- acts at long ranges
- often slowly
- on distant organs or tissues
what are the types of actions by hormones?
- paracrine (hormone is released and acts upon adjacent cell)
- autocrine (hormone is released and acts upon the same cell that it was released from)
- neurocrine (messenger is released from one neurone, to act on the next neurone)
- endocrine (hormone is secreted directly into the circulation)
- neuroendocrine (messenger is released from a neurone into the circulation)
what type of hormone action is histamine release from mast cells?
paracrine
what type of hormone action is interleukin release?
autocrine
what type of hormone action is dopamine inhibition of prolactin release?
neuroendocrine
why is the endocrine system important?
- maintains internal environment
- in response to changes in the external environment
- important for growth and development, puberty and sexual maturation
what is thyroxine?
- a thyroid hormone
- derivative of tyrosine
- with added iodine molecules
what are the catecholamine derivatives of tyrosine?
- adrenaline
- dopamine
what are the four glycoprotein hormones?
- thyroid stimulating hormone (TSH)
- follicle stimulating hormone (FSH)
- luteinising hormone (LH)
- human chorionic gonadotropin (hCG)
what are glycoprotein hormones made up of?
- alpha (species specific) and beta chain (hormone specific)
- carbohydrate
what are the three steroid hormones?
- mineralocorticoids (affects water and electrolyte balance)
- glucocorticoids (affects carbohydrate and protein balance)
- sex steroids (affects sexual characteristics)
give an example for each type of steroid hormone
- mineralocorticoids (aldosterone)
- glucocorticoids (cortisol)
- sex steroids (oestrogen, testosterone, progesterone)
describe the receptor mechanism between adrenaline and protein kinase A
- adrenaline binds to a G protein coupled beta adrenoreceptor
- this activates adenylyl cyclase
- this increases intracellular concentrations of cAMP
- this activates protein kinase A, to provide the catalytic unit which can phosphorylate other enzymes to produce a response
describe the receptor mechanism involving PLC, DAG, IP3 and protein kinase C
- ligand binds to receptor which activates Gq protein
- this activates PLC, which acts on membrane phospholipids to form DAG and IP3 (second messengers)
- IP3 binds to endoplasmic reticulum and causes the release of calcium
- DAG acts on protein kinase C to activate it, which also elevates intracellular calcium concentrations
- other enzymes become phosphorylated to produce a response
what hormones circulate in free form and bound form?
- catecholamines: free form
- thyroid hormones: mainly bound form
- proteins/peptides: mainly free form
- steroid hormones: mainly in bound form
what is the chain of enzymes to get adrenaline from tyrosine?
- tyrosine
- DOPA
- dopamine
- noradrenaline
- adrenaline
how are different hormones stored and released?
- catecholamines: stored in secretory granule or vesicle
- peptide hormones: stored in secretory granule, released via exocytosis due to Ca2+ conc. contents are released while the granule is recycled
- thyroid hormones: stored in a colloid as part of thyroglobulin
- steroid hormones: not stored, made from cholesterol which are stored in lipid droplets.
what are the type of releases of hormones?
- pulsatile: episodic release of hormone
- circadian: based of a 24hr cycle
- diurnal: synchronised to day/night
- infradian: based on longer than 24hr cycle
- seasonal
how are oestrogen and progesterone released in women?
- hypothalamus releases GnRH
- which acts on anterior pituitary
- causes releases of FSH and LH to the ovaries
- FSH causes follicle maturation and the release of oestrogen
- LH acts on the corpus luteum and causes the release of progesterone
- both oestrogen and progesterone act in a negative feedback system with the anterior pituitary, to stimulate or inhibit the release of FSH and LH
- progesterone can also act in a negative feedback system with they hypothalamus to stimulate or inhibit the release of GnRH
how does a pulsatile release of GnRH from the hypothalamus affect FSH and LH?
- releases FSH and LH
how does a sustained release of GnRH from the hypothalamus affect FSH and LH?
- inhibits release of FSH and LH
describe the hormone binding of catecholamines and protein peptides
- largely hydrophilic
- do not associate with plasma proteins
describe the hormone binding of steroid hormones and thyroid hormones
- lipophilic
- highly bound to plasma proteins
what is the scientific name for the pituitary gland?
hypophysis
what is the pituitary gland divided into?
- anterior lobe (adenohypophysis) contains endocrine hormones
- posterior lobe (neurohypophysis)
describe the organisation of the hypothalamus and pituitary (supraoptic nucleus)
- nerves in the supraoptic nucleus make contact with capillaries in the portal system (runs from the hypothalamus to the adenohypophysis)
- neurones release factors into portal system, which stimulate or inhibit release of hormones from endocrine cells
describe the organisation of the hypothalamus and pituitary (paraventricular nucleus)
- nerves in paraventricular nucleus make contact with neurohypophysis)
- hormones are directly released into blood supply and are carried away by venous drainage
- to present their effects onto the peripheral system
what is a tropic hormone?
a hormone released by an endocrine gland, which acts upon another endocrine gland
what is a trophic hormone?
a hormone which stimulates growth in target tissues. they may cause hypertrophy (increase in cell size) or hyperplasia (increase in cell number)
explain the hypothalamic-pituitary axis
- CNS input + other input
- hypothalamus
- releasing hormone
- anterior pituitary
- tropic hormone
- peripheral gland (endocrine gland that is not in the nervous system)
- hormone
- target
- effect
how many hormones are produced by the anterior pituitary?
6
what hormones are produced by the anterior pituitary?
- FSH (follicle stimulating hormone)
- LH (leutinizing hormone)
- TSH (thyroid stimulating hormone)
- ACTH (adrenocortico tropic hormone)
- prolactin
- GH (growth hormone)
what do FSH and LH act upon?
testes, ovaries
what does TSH act upon?
thyroid gland
what does ACTH act upon?
adrenal gland
what does prolactin act upon?
mammary glands
what does GH act upon?
bones, tissues, liver
what is somatostatin?
growth hormone release inhibiting hormone
what is inhibin?
a hormone produced by the ovaries, which feed back to the gonadotropes in the anterior pituitary; inhibiting the release of FSH
describe the control of hormone production in males with FSH and LH.
- hypothalamus releases GnRH to the gonadotropes in the anterior pituitary
- this releases FSH and LH to the testes
- LH acts on Leydig cells in the testes, which produces testosterone.
- LH and FSH acts on Sertoli cells, which are involved in spermatogenesis
- the increase in testosterone inhibits the hypothalamus and anterior pituitary from GnRH, FSH and LH release respectively
- Sertoli cells produce inhibin which acts upon the anterior pituitary to inhibit the release of FSH and LH
when is the secretion of prolactin increased?
- during pregnancy (to promote additional breast development)
- during lactation (production of milk)
what is the prolactin inhibitory factor?
dopamine
- acts on D2 receptors to inhibit prolactin release
what is the prolactin releasing factor?
thyrotropin releasing hormone
how is the release of prolactin controlled?
- suckling of the breasts stimulates mechanoreceptors in the nipple
- this sends signals to the hypothalamus, which inhibits the release of dopamine to the anterior pituitary
- this means more prolactin is released to the milk gland cells in the breasts, ultimately stimulating milk production.
- mechanoreceptors sending signals to the hypothalamus also stimulates oxytocin release from the posterior pituitary to the myopepithelial cells in the breasts
- this ultimately stimulates milk ejection by contraction
what is the role of prolactin and oxytocin in milk production?
prolactin - stimulates milk gland cells to produce milk
oxytocin - stimulates myoepithelial cells to eject milk through contraction
what is hyperprolactinaemia?
excess production of prolactin
- causes galactorrhea (excess milk secretion)
- causes gynaecomastia (excess breast growth in both males and females)
- causes infertility
how would you treat hyperprolactinaemia?
- D2 agonists
- bromocriptine
- cabergoline
what effects do growth hormone have on blood glucose levels?
- increases blood glucose levels
- by having anti-insulin effects
what are the actions of growth hormone?
- stimulates growth of long bones until fusion of epiphysis
- increase in size of viscera
- anabolic effects of protein
- catabolic effects on fat and carbohydrates
what does hypersecretion of growth hormone cause clinically?
hypersecretion:
- gigantism (body grows very tall) before fusion of epiphysis
- acromegaly (abnormally large hands and feet) after fusion of epiphysis
what does hyposecretion of growth hormone cause clinically?
hyposecretion:
- short stature before fusion of epiphysis
- adult growth hormone deficiency after fusion of epiphysis
what are the two posterior pituitary hormones?
- oxytocin
- arginine vasopressin
- differ by amino acids 3 and 8
- both hormones have 2 Cys and disulphide bridge
how are oxytocin and arginine vasopressin synthesised?
- neurophysins are precursors in the cell bodies of the supraoptic nucleus and paraventricular nucleus
- neurophysin 1 is associated with the synthesis of oxytocin
- neurophysin 2 is associated with the synthesis of arginine vasopressin
what is another name for arginine vasopressin?
anti-diuretic hormone (ADH)
what stimulates the release of arginine vasopressin (ADH)?
- decrease in total body water
- decrease in blood pressure
- hyperosmolarity (detected by hypothalamic osmoreceptors)
- low plasma vol (detected by baroreceptors)
- angiotensin II
what are the actions of arginine vasopressin (ADH)?
- increase in water reabsorption to increase blood volume
- vasoconstriction to increase systemic vascular resistance
- these both ultimately cause the increase in blood pressure
where is the thyroid located and what does it consist of?
- sits on trachea
- 2 lobes joined by an isthmus
when does the thyroid become an enlarged?
- during pregnancy
- during lactation
- in adolescence
- during later portion of menstrual cycle
what is the blood supply to the thyroid gland and where does this originate from?
- superior and inferior thyroid arteries
- which arise from the external carotid artery and subclavian artery
where are parathyroid glands located?
embedded between the thyroid glands
what is the function of parathyroid glands?
- to produce parathyroid hormone
- which is involved in Ca2+ metabolism
- parathyroid hormone is released during low plasma Ca2+ concentration levels
- to raise Ca2+ concentration levels
what are the types of cells in a thyroid gland?
- follicular cell: responsible for making thyroid hormones
- parafollicular cell/ C cell: involved in Ca2+ metabolism, when Ca2+ concentration in the plasma is high
what controls the basal metabolic rate?
- thyroid hormones
what is calcitonin?
a peptide hormone secreted by parafollicular cells
how is the synthesis and release of thyroid hormones regulated?
- hypothalamus releases thyrotropin releasing hormone (TRH)
- TRH stimulates thyrotrophs in anterior pituitary to release TSH or thyrotropin
- TSH stimulates thyroid gland to synthesise and release thyroid hormones
what protein is the main component of the colloid?
thyroglobulin
what is actively transported into the follicular cell?
iodine via a sodium/iodide transporter
what causes oxidation and activation of the iodide inside the follicular cell, at the apical membrane?
thyroid peroxidase
what is oxidised iodine used for in terms of thyroid hormone synthesis?
it is added to tyrosine residues in the thyroglobulin to form thyroid hormones
what is T3 and T4?
- T3: tri-iodothyronine
- T4: thyroxine
what type of receptors do thyroid hormones interact with?
nuclear receptors
how do thyroid hormones enter a cell
- diffusion
- or specific carrier
what happens when T4 (thyroxine) is taken up into cells?
- deionisation into T3, which enters the nucleus and binds to the thyroid receptor
- thyroid receptor dimerises with retinoid X receptor
- this binds to thyroid hormone responsive element, which targets gene expression
what is hashimoto’s thyroiditis?
- autoimmune disease
- hypothyroidism
- one produces antibodies to thyroglobulin or thyroid peroxidase
- this prevent’s the synthesis of thyroid hormones
- commonly treated with thyroxine
what organ is the adrenal gland associated with?
kidney (adrenal gland sits on top of kidney)
what are the two portions of the adrenal gland called?
- outer portion: adrenal cortex
- inner portion: adrenal medulla
what are the three layers of the adrenal cortex called?
- zona glomerulosa
- zona fasciculata
- zona reticularis
what hormones do the adrenal medulla secrete?
- 80% adrenaline
- 20% noradrenaline
what class of hormones does the adrenal cortex secrete?
steroid hormones
what does the zona glomerulosa lack and what hormone does it secrete?
- lacks 17 alpha hydroxylase
- secretes aldosterone
what does the zona fasciculata lack and what hormone does it secrete?
- doesn’t lack 17 alpha hydroxylase
- lacks aldosterone synthase
- secretes cortisol
what does the zona reticularis lack and what hormone does it secrete?
- lacks aldosterone synthase
- secretes androstenedione and DHEA
explain the regulation of cortisol synthesis in the adrenal cortex
- hypothalamus secretes corticotropin releasing hormone (CRH)
- CRH acts on the corticotrophs of the anterior pituitary to secrete adrenocorticotropic hormone (ACTH)
- ACTH stimulates the adrenal cortex to synthesise and release cortisol
- cortisol feeds back to the corticotrophs of the anterior pituitary to decrease the release of ACTH and on the hypothalamus, to inhibit release of CRH
what receptors does cortisol act upon?
glucocorticoid receptors
what is a circadian rhythm?
24hr cycles that are part of the body’s internal clock. they are physical, mental and behavioural changes
ie. body reaches highest body temp at 7pm
what factors stimulate CRH release from the hypothalamus?
- circadian rhythms
- stress
what type of receptor does ACTH act upon?
- melanocortin 2 receptor
- MC2R (G-protein coupled receptor)
what happens when ACTH binds to its MC2R receptor?
- activates adenyl cyclase
- which increases cAMP levels
- activates protein kinase A
- which activates cholesterol ester hydrolase, allowing the release of cholesterol from lipid droplets
- protein kinase A also stimulates desmolase, the rate limiting step
- this leads to increased synthesis of cortisol
how is cholesterol converted into cortisol?
- cholesterol (after being released from lipid droplets) is taken up by the mitochondrion
- it is converted into pregnanolone using cholesterol desmolase
- pregnanolone is transferred to the SER, where it is converted to 11-deoxy-cortisol
- 11-deoxy-cortisol is taken up by the mitochondrion again and converted into cortisol
- cortisol is highly lipid soluble, so it then diffuses out of the cell
how do steroid hormones lead to an increase in gene transcription?
- due to its lipophilic nature, steroid hormones diffuse into the cell and bind to a cytoplasmic receptor.
- this causes the dissociation of the heat shock protein on the receptor
- the hormone-receptor complex dimerises and translocates to the nucleus (steroid hormones can interact with nuclear receptors)
- the complex binds to a specific hormone responsive element on DNA, which increases mRNA production, and subsequently increases protein synthesis
what receptor does cortisol have a higher affinity for?
mineralocorticoid receptor > glucocorticoid receptor
how is cortisol’s higher affinity for mineralocorticoid receptors managed?
- 11 beta hydroxysteroid dehydrogenase is an enzyme that has two isoforms and can either convert cortisol (active) to cortisone (inactive,) or the other way round
where are the two isoforms of 11b-HSD expressed?
- 11b-HSD1 is expressed in the liver, adipose and muscle tissue (converts cortisone into cortisol)
- 11b-HSD2 is expressed in aldosterone sensitive tissues (converts cortisol into cortisone)
what are the adverse effects of glucocorticoids?
- increase in blood glucose
- hyperglycaemia
- decrease in bone density
- osteoporosis
- suppression of response to infection
- suppression of endogenous glucocorticoid production
- iatrogenic Cushing’s syndrome (prolonged exposure to high levels of circulating cortisol)
what are the effects of Cushing’s syndrome?
- increased susceptibility to infection
- increased appetite
- obesity
- osteoporosis
- negative nitrogen balance
- (may be caused by Cushing’s disease which is a pituitary tumour that leads to increased production of ACTH)
what are the effects of aldosterone?
- effects on the distal tubule and collecting duct of the kidney
- increase number of Na+ channels in the apical membrane
- increase in Na+/K+ ATPase channels in the basolateral membrane
- leads to increased Na+/K+ exchange
what is spironolactone?
- aldosterone antagonist
- used as sparing K+ diuretic
what is Addison’s disease?
- chronic adrenal insufficiency
- primary adrenal insufficiency due to destruction of adrenal cortex (unable to produce either cortisol or aldosterone)
- secondary adrenal insufficiency due to lack of ACTH
what are the clinical features present for Addisons’s disease?
- weakness, fatigue, anorexia, weight loss
- gastrointestinal disturbances
- hypotension
- hyperpigmentation
- salt craving
- postural symptoms
what treatment is available for Addison’s disease?
- replacement therapy with fludrocortisone
what is the principle mineralocorticoid secreted from the adrenal gland?
- aldosterone
- secreted from the zona glomerulosa
- acts on the renal distal convoluted tubule to promote the retention of sodium and excretion of potassium
