Endocrine System Flashcards
What is the meaning of endocrine?
hormone that is produced and secreted within the body, acts at a distance from the release site
What is the meaning of exocrine?
hormone which is secreted outside the body
What is paracrine?
acts on nearby cells
What is autocrine?
acts on its own secreting cell
What is neuroendocrine?
synthesized by nervous tissue and carried in blood
What is a gland?
cluster of cells organized for synthesis/release of compound, glands can be exocrine or endocrine
What is a hormone?
regulatory chemicals produced in an endocrine gland or scattered cells, secreted into the blood and carried to its target cell that responds by altering its metabolism
- Involved in maintaining homeostasis
- Subjected to tight regulation by feedback from target organs
- Regulation of hormones synthesis and mode of action differ greatly based on their structure
What is feedback control?
cyclic loops that control the amount of hormone released
What is a steroid hormone?
stepwise conversion of cholesterol by multiple enzymes
What type of solubility do steroid hormones possess?
lipid-soluble = leave production cells and enter target organ by diffusion throguh the membrane
What are peptides, proteins and glycoproteins made out of?
chains of amino acids = sequence determines the primary structure and nature
What are the steps of turning DNA into a protein?
DNA -> (txn in nucleus) mRNA -> (tln in ribosome or cytosol) protein
What are two types of post translational modifications of proteins?
glycosylation = carbohydrate chains attached
phosphorylation = phosphate group attached
Where are proteins modified/packaged?
in ER and golgi
How are proteins secreted?
exocytosis
What are two hormones that are amino acid derivatives?
thyroid hormones and catecholamines which are generally derived from tyrosine and tryptophane
What is a hormone that is a fatty acid derivative?
prostaglandins, derived from cell membrane phospholipids (arachidonic acid)
Where are fatty acid derived hormones produced and what type of effects can they have?
produced locally, have mainly autocrine, paracrine effects
Where is the pineal gland located?
roof of the 3rd ventricle encapsulated by meninges
What does the pineal gland secrete?
melatonin
What is the pineal gland under influence by?
direct influence of the hypothalamic circadian center
What is the role of the pineal gland and when is it secretion necessary?
major role during sleep patterns and recognition of seasons, melatonin secretion is stimulated during dark phases
What are the hormone secretions of the GI tract?
Stomach wall: gastrin, local stimulation of acid secretion
SI
- secretin: stimulates pancreas
- cholecystokinin: stimulates pancreas and gall bladder
- gastric inhibitory peptide: inhibits stomach activity
What are the hormone secretions of the kidney?
renin: increases aldosterone secretion by adrenal cortex
erythropoietin: increases production of RBCs in bone marrow
What are the hormone secretions by the adipose tissue?
adipocytes release leptins and other adipokins
Where can leptin receptors be found?
in the hypothalamus
What do leptins give us information about?
energy storage status, and regulates appetite
Draw out the table in Endocrine I
refer to slides
What are the functions of hormones?
hormones are secreted in the blood and act at a distance from the release site, they need to travel in the blood (solubility), survive long enough and be active at the target site, hormones trigger specific actions in specific target cells, principle of action is based on hormone biochemical structure/properties
What is the requirement for hormone recognition?
a receptor
What are the two types of hormones?
lipophillic hormones
water soluble hormones
What are some properties of lipophillic hormones?
- insoluble in water
- diffuse out of producing cells
- circulate mainly bound to carriers in the blood
- diffuse in target cells: intracellular receptors
What are some properties of water soluble hormones?
- secreted (exocytosis)
- circulate free in the blood (except IGF-1)
- stay out of target cell: surface extracellular receptor
- cannot pass the phospholipid membrane barrier
What are two lipophillic hormones?
steroid and thyroid hormones
What are some specific and non-specific carrier proteins for lipophillic hormones?
specific - globulins (CBG, DBG, SHBG, TBG)
non-specific - albumin and prealbumin
What is a distinct characteristic of lipohillic hormone carrier proteins?
they are big, they keeps the hormones in the vessel and prevent hormone degradation
What happens to the lipophillic hormone not bound to a carrier protein?
remains free and diffuses to the tissues
What makes a lipophillic hormone active?
free hormones not bound to carrier proteins, however these hormones are also susceptible to degradation
Are bound or free hormones involved in feedback loops?
free form
What is the point of a carried hormone?
serves as a hormone reservoir, hormone buffer and hormone protector
Draw the graph of the carrier protein chart from endocrine II
refer to slides
Describe how lipophillic hormones take action on target tissue
- free hormones diffuse through PM of target
- binds to a specific intracellular recepor (nuclear hormone receptor - NHR)
- hormone-receptor complex translocates to the nucleus and binds to specific DNA sequence (response element)
- stimulates gene expression - de novo protein synthesis
- after acting, hormones dissociate form the receptor, can be partly degraded in target cells (T3/4) and then goes back to circulation and degraded in the liver
What is NHR considered?
txn factor
What is the special case of NHR in thyroid hormones?
NHR is already in the nucleus and hormones diffuse all the way there
What are the four parts of a nuclear hormone receptor (NHR)?
ligand binding domain: binds hormone
DNA binding domain: binds DNA of the target gene
activation domain: stimulates gene transcription
orphan receptor: NHR cloned but no ligand found (yet)
Are lipophillic hormones slow or fast acting?
slow - the action affects the synthesis of new proteins by gene regulation
What are some special characteristics of water soluble hormone action?
- secreted in vesicle by exocytosis
- bind to specific receptors on surface of target cell
- do not enter the cell to act: need second messengers
- receptor is key mediator between hormone and second messenger
What are two types of water soluble hormone?
proteins and catecholamines
What type of hormone has a cell surface receptor?
water soluble
How do cell surface receptors work? Structure?
- hydrophobic region: hiding in the membranes phospholipids (TMD)
- hydrophilic regions located outside (exracellular domain ECD) and inside (intracellular domain ICD) the cell
- hormone receptor: activated of intracellular second messengers
What are the major types of cell surface receptors and their second messengers?
G-proteins coupled: adenylate cyclase (cAMP) and phospholipase C (Ca2+)
tyrosine kinase: auto phosphorylation
interleukin/cytokine family: JAK-STAT
serine kinase (TGFbeta) family: SMADs
What is the G-protein coupled receptor pathway?
- hormone binds to a receptor coupled to g-proteins
- change in receptor conformation = exchange of GDP with GTP on Galpha SU
- Galpha SU dissociated from beta gamma SU and activates a membrane protein
- activated membrane protein stimulates a cascade of second messengers
- the second messengers elicit the biological response in the cell
How many major types of G-proteins are there?
3
What is the adenylate cyclase-cAMP-pKA characteristics?
- receptor coupled to G-proteins alpha(s) or alpha(i)
- membrane associated enzyme is Adenylate cyclase (AC)
- Galpha(s) stimulates AC; Galpha(i) inhibits AC
- AC hydrolyses ATP into cyclic AMP (cAMP)
What is the phospholipase C pathway (PLC)?
- receptor coupled to G-protein alpha(q)
- membrane associated protein is PLC
- Galpha(q) stimulates PLC
- results in the activation of: Ca2+ and protein kinase C = phosphorylation cascade followed by biological action
What is the tyrosine kinase receptor pathway?
- binding of hormone
- activation of receptor
- autophosphorylation
- becomes a kinase
- phosphorylates tyrosines on target proteins
Does the tyrosine kinase receptor need a second messenger?
no, it directly phosphorylates target proteins
What are the three domains of a tyrosine kinase receptor?
- transmembrane domain
- extracellular domain for ligand recognition
- cytoplasmic domain with autophosphorylation site that transmits regulatory signals and contains ATP binding sites
What are the receptors for cytokines?
GH, prolactin, erythropoietin, interferons and interleukins
Do receptors for cytokines have intrinsic kinase activity?
no
What are some characteristics of cytokine receptors?
- receptor exists as monomer, binding of hormone causes dimerization and binding of JAS tyrosine kinase which phosphorylates the receptor
- phosphotyrosine act as docking sites for intracellular signalling molecules - STATs which activate various genes
How does the serine kinase receptor work?
- binding of hormone results in heterodimer formation: receptor I + receptor II
- RII is specific to the hormone. after binding, H-RII complex recruits RI (same RI can be recruited by different H-RII complexes)
- serine residues on RI get phosphorylates by RII
- activated receptor phosphorylates Smads proteins that will dimerize, translocate in the nucleus and modulate gene txn
What is a serine kinase receptor?
TGFbeta family (activin, inhibitin, MIS) mainly involved in control of cell proliferation and differentiation
How do cell surface receptors have a large impact?
cascade of intracellular messengers amplifies the signal several thousand times
What do actions on the target cells depend on for cell surface receptors?
specific effects on target cells depend on the type and amount of messenger activated
What are two types of effects of a hormone?
immediate effect: enzyme activation, exocytosis
slow effect: stimulation of gene txn, de novo protein synthesis
What happens to the receptor-hormone complex after signal is transmitted?
receptor-hormone complex is internalised
- fuses to lysosome and is degraded
- dissociates and receptor is recycled to cell surface
What are some characteristics of the hypothalamus?
major integration center
- part of the brain
- regulates ANS and most of endocrine
- processes most sensory info
Where is the pituitary gland located?
- small gland attached to the hypothalamus
What are the three parts of the pituitary gland?
posterior lobe: neurons from hypothalamus
anterior lobe: major endocrine part (glandular tissue)
intermediate: major function in amphibians and fish
What is the hypothalamo-pituitary axis?
the major form of communication between the hypothalamus and the pituitary
Describe how the hypothalamo-pit axis works
since the hypothalamus is composed of neuroendocrine cells some project axons down post pit and some release factors into pit stalk portal venous system to feed the anterior pit
- endocrine cells from ant and int pit release their hormones in a second capillary network to enter systemic circ
What is the role of the intermediate pit in mammals?
produces MSH (melanocyte stimulating hormone which increases skin pigment)
produces beta LPA: which is released during stress (analgesia)
What are the two hormones that the post pit releases?
ADH (vasopressin) and oxytocin
Where are oxytocin and ADH produced?
In cell body of hypothalamic neurons
How are oxytocin and ADH released from the post pit?
transported to the pit along axons in vesicles, stored in nerve endings, released when AP is fired, after secretion, hormones diffuse into blood vessels
What is the role of ADH?
regulates extracellular fluid
acts in the kidneys: regulates the density of aquaporins (water channels) in the distal tubule and collecting duct
ADH increases the reabsorption of water
What is ADH primarily regulated by?
hypothalamic osmoreceptors and stretch receptors in blood vessels
What is the primary action of oxytocin?
uterus smooth muscle: contraction during parturition
mammary gland: contraction increases pressure to drive milk towards excretory ducts and the teas (milk ejection reflex)
What is the receptor for oxytocin?
G-coupled receptor with activation of PLC (Ca pathway)
What is the secretion of oxytocin regulated by?
reflexes such as stimulation of the teat
How many cell types are there in the anterior pit?
endocrine part has 5 different cell types
How many hormones are produced in the ant pit in the endocrine part?
6 different
What are the 6 hormones that the ant pit releases?
TSH (thyroid stimulating hormone) - thyrotrope
LH/FSH (gonadotropins) - gonadotrope
ACTH (adrenocorticotropin) - corticotrope
GH (growth hormone) - somatotrope
PRL (prolactin) - mammotrope (lactotrope)
What are tropic effects?
regulation of other endocrine glands
Is the ant pit under direct control of the hypothal?
yes
What are the direct and indirect effects of growth hormone?
direct: stimulates lipolysis and reduces lipogenesis in adipose tissue (catabolic); promotes synthesis of protein (anabolic)
indirect: by stimulating synthesis of IGF1 (somatomedin) and its binding proteins in the liber. Stimulates chondrocyte (cartilage cells) proliferation to increase bone growth; stimulates satellite cells in muscle (muscle fiber growth); stimulates AA uptake and protein synthesis
What is the receptor type for growth hormone?
cytokine receptor
What is the function of TSH?
TSH binds to is G-coupled receptor on membrane of follicular cells in thyroid gland stimulates cAMP pathway which in turn stimulates the synthesis of TH (will be described in more details)
What is the function of ACTH?
ACTH receptor is a G-coupled receptor stimulating the cAMP pathway, stimulates the mobilisation of cholesterol in adrenal cortex - more substrate for cytochrome P-450 -> increases release of corticosteroids
What is the receptor for TSH?
G-coupled receptor
What is the receptor for ACTH?
G-coupled receptor
What is the function of LH?
male: stimulates testosterone production by leydig cells in the testis
female: controls sex steroid production by the ovary and is responsible for ovulation (surge)
What type of receptor does LH use?
G-coupled receptor cAMP pathway
What is the function of FSH?
male: stimulates secretion of inhibin by sertoli cells
female: development of follicles and secretion of sex steroid?
What is the receptor for FSH?
G-protein coupled receptor
What is the function of prolactin? (PRL)
stimulates the synthesis of milk proteins (casein, lactalbumin)
in poultry, responsible for the initiation and maintenance of incubation behaviour (broodiness)
How are neurohormones released in the hypothalamic control fo the ant pit?
neurohormones released in small amount (bypass general circulation)
Where does the hypothalamic neurons receive information from?
- higher brain center, emotions
- exterior, environmental and social stimuli
- internal rhythms
- metabolic state (temperature, energy level, osmolarity)
- endogenous hormones by feedback
What are the inhibitors and stimulators of the pituitary hormones?
GnRH - stimulates FSH and LH
GnIH - inhibits FSH and LH
ACTH-RH - stimulates ACTH
TRH - stimulates TSH
GH-RH - stimulates GH
GH-IH - inhibits GH
Dopamine - inhibits prolactin
VIP in birds - stimulates prolactin
Which hormones are under tonic inhibition?
GH, MSH, PRL
When are tonically inhibited hormones activated?
early in life. as the hypothal ages and matures, secretion decreases
where are releasing hormone precursors made?
in cell bodies and transported down the axons to the nerve endings for storage
What happens when an electric stimulus reaches hypothalamus?
electrical stimulus = released by hypothalamus -> delivered to pit by portal system -> release of hormone by pit -> release of ultimate hormone in target gland, amplification of signal at each step
What is the motion of the hormone/pituitary hormone release?
pulsatile/episodic
- regulated by biological clock of hypothalamic suprachiasmatic nucleus
What does pulsatility prevent?
may prevent the down regulation of receptors from continuous level of hormone secretion, can trigger specific action depending on pulse frequency
What are the two types of loops?
short loop: pit hormones feed back to hypothalamus
long loop: hormones from target glands feed back to the pit and hypothal
What is negative feedback?
circulating hormones from endocrine glands provide negative feedback both to the hypothalamus and pit, feedback serves to regulate the secretion of hormones
What is the main functions of GH?
- promotes tissue and body growth in young animals, especially longitudinal growth until skeleton is complete, regulates lipids and protein metabolism
- in adults, GH mainly controls metabolism
- during fetal life, GH does not stimulate growth; this role is played by insulin like growth factors (IGF1 and 2)
- GH decreases glucose utilization in most tissues, GH increases concentration of bld glucose
Does GH protein sequence differ?
differs a lot between species (poor cross reactivity)
What regulates GH?
GHRH stimulates GH
GHIH inhibits GH
very precise dual regulation
What does GH stimulate?
IGF1 production by the liver
What does IGF1 stimulate?
cartilage and bone growth and milk production
What instances makes levels of GH change?
- circadian pattern: increases during sleep
- high AA and low glucose content in plasma both increase GH secretion (high protein diet, long fasting)
- exercising and stress also increase GH secretion
- sex steroids increase GH secretion = burst of growth at puberty
- IGF1 responsible for negative feedback on GH secretion
What is the half life of GH?
20 minutes (short)
What cells does GH affect?
most cells
How is GH an anabolic and catabolic hormone?
anabolic: like insulin GH promotes synthesis of protein
catabolic: conversely to insulin, GH stimulates lipolysis and reduces lipogenesis in adipose tissue (important during fasting and at night) lypolysis increases FA prod.
What are the indirect roles of GH via IGFs?
- stimulates synthesis of IGF1 and its binding proteins in the liver, small amounts also locally produced in muscle/adipose tissue
- IGF1 stimulates chondrocytes (cartilage cells) proliferation to increase bone growth
- IGF1 stimulates satellite cells in muscles (muscle fiber growth)
- IGF1 stimulates AA uptake/protein synth
What is the structure of IGF1?
polypeptide chain with similar sequence in human, porcine, bovine
What is IGFs half life?
much longer than GH, bound to carrier proteins
How does IGF1 act?
via its own tyrosine kinase receptors
Does GH have a major role in mammary gland development?
no
How does GH have an effect on milk production?
mediated via metabolism, and partitioning nutrients to the mammary gland for milk synthesis
Why is GH injection a concern for humans?
infant can absorb GH and IGF in the gut
What is the consequence of overproduction of GH?
before puberty: gigantism
after puberty: acromegaly, increased bone width and density, diabetes
What are the consequences of lack of GH production?
dwarfism, in dogsm dwarfs keep their puppy coat for a long time, lack of IGF1 action on hair follicle differentiation
What is the cause of lack of GH?
genetic defects of GH or GH receptor genes
What is the cause of overproduction of GH?
in old dogs and cats, usually due to pituitary tumor
What is the solution to lack of GH production?
injection of recombinant GH and IGF1
What two types of gland is the pancreas?
exocrine and endocrine gland
What are the cell types in the endocrine pancreas?
islets of langerhans (scattered throughout the pancreas)
What are in the islets of langerhans?
beta cells (70%) secrete insulin and alpha cells (20%) secrete glucagon
insulin/glucagon have opposite effects
How is insulin made before secretion?
produced as preprohormone, converted to proinsulin, before secretion, converted to active insulin by removing a connecting C peptide
How long does insulin circulate?
circulates free half life of 5-8 mins
Where is insulin degraded?
in target cells or in liver
How is glucagon made before secretion?
29 AA peptide produced as a preprohormone rapidly converted to active glucagon
After secretion, where and how does glucagon circulate?
free (half life of 5 min) and is metabolized in the liver and kidney
Is insulin anabolic or catabolic?
anabolic
What is the overall actions/effects of insulin?
- through tyrosine kinase receptor, insulin leads to the upregulation of membrane glucose transporters -> cellular uptake of glucose in muscles and adipose tissue
- insulin stimulates incorporation of glucose in energy storage molecules: glycogen in liver and muscle, and triglycerides in adipose tissue
- insulin promotes uptake of AA
- overall effects lead to decrease in blood glucose and AA levels
What are the actions/effects of glucagon?
- through its G-protein coupled receptor glucagon activates enzyme responsible for glycogenolysis -> release of glucose from glycogen by the liver
- glucagon also stimulates gluconeogenesis in the liver (synthesis of glucose)
- glucagon stimulates release of FA from triglycerides in adipose tissue
What are the two things that regulate insulin and glucagon secretion?
- major mechanism of regulation of insulin and glucagon is the blood glucose concentration
- to a lesser extent AA concentration
How does the autonomic nervous system affect insulin/glucagon secretion?
parasympathetic: during meals, it activates insulin secretion
sympathetic inhibits insulin secretion and stimulates glucagon release “stress hyperglycemia”
What is diabetes?
hyperglycemia, when blood levels exceed kidney reabsorption capacity -> glycosuria -> increase osmolarity of urine -> increase in urine volume (diabetes), sweet (mellitus)
What is the difference between type I and type II diabetes?
Type I: insulin dependent diabetes, insuline secretion is impaired
Type II: insulin independent diabetes, insulin secretion normal but tissues are insensitive
Where is the thyroid gland located?
located on both sides of the trachea, below the larynx, two lobes bridged by isthmus, heavily vascularised
What are the follicles that the thyroid gland is composed of?
single layer of epithelial cells that release thyroid hormones
lumen filled with protein rich fluid (colloid)
between follicles, parafollicular cells (c-cells) secrete calcitonin
How are thyroid hormones synthesized?
- active uptake of iodine
- iodine circulates in blood as iodide
- actively transported through follicular cells
- diffuses and accumulates in colloid as iodine - iodination of thyroglobulin
- Tgb, a glycoprotein with over 120 tyrosine residues, is released in the lumen
- tyrosine peroxidase (TPO) binds I2 to tyrosine residues - Tgb I2 up-taken by endocytosis form colloid into cells, fused to lysosomes and split into thyroid hormones
How much of Tgb is iodinated in the colloid?
10%
How many sites can each tyrosine residue be iodinated?
each tyrosine residue can be iodinated on possible 2 sites
1. I2 tyrosine - monoiodotyrosine
2. I2 tyrosine - diiodotyrosine
What are T4 and T3 made up of?
T4 - 2 diiodothyrosines = tetraiodothyrone
T3 - 1 monoiodotyrosine + 1 diiodotyrosine = triiodothyronine
What percent of thyroid hormones is T3 and what percent is T4?
T3 - 10%
T4 - 90%
What happens after T3 and T4 are created?
lypophilic hormones diffuse across basal membrane into interstitial space then into blood capillaries, in blood, binds to plasma proteins
How much does TBG bind to thyroid hormones?
TBG binds 70-80% of circulating thyroid hormones, remaining is bound to other albumins
How much free T3/T4 is circulated free in the blood?
0.03% are free in blood and diffuse to tissues
What happens to thyroid hormones after they diffuse in target cells?
T4 is deodinated to T3 (active form) binds to its nuclear receptor and activates gene txn, affinity of receptor is higher for T3 than T4
What are some functions of thyroid hormones?
- act on all cells of the body to increase BMR which increases heat production, O2 consumption (except brain, gonads and spleen)
- during development, thyroid hormones stimulate secretion of GH -> important for bone growth and tissue growth
- during last phase of fetal development and early stage after birth, TH are critical for normal maturation of brain function
- TH increase the number of adrenalin/norad receptors -> boost sensitivity to sympathetic system
- essential for gonadal function
- increase nerve conduction velocity
What is the metabolism of thyroid hormones?
- deiodination to reverse T3 in target tissues results in deactivation
- after deactivation, diffuses out of target cell and is processed in the liver
- the I2 release during metabolism can be recycled to thyroid
What happens when TRH is released from the hypothalamus?
increases TSH secretion from the pit
How does TSH work?
binds to its G-coupled receptor on membrane of follicular cells, stimulates cAMP pathway which in turn stimulates the endocytosis of Tgb I2 and the synthesis of TH, TH exerts a negative feedback on both pit and hypothalamus
What happens to TRH when exposure to cold occurs?
exposure to cold for long period increases TRH release
If metabolites decrease (fasting) what happens to T3/T4?
T3/T4 rapidly decrease
What is hypothyroidism?
in humans, mainly associated with iodine deficiency, results in reduced growth/mental retardation
in dogs most cases result from autoimmune disorders that destroy follicular cells = primary hypothyroidism
secondary hypothyroidism - low secretion of TSH, mainly due to injury to pit or hypothalamus
What are some effects on the body of hypothyroidism?
- reduced heat production and tolerance to cold
- sluggish animal, not feeding but gaining weight
- impaired reproduction, constipation
What is the treatment for hypothyroidism?
thyroxine for the rest of the life
What is goiter?
enlarged thyroid gland
What are the causes of goiter?
deficiency in iodine, tumor and inflammation, lack of thyroid hormones increase TRH and TSH release (lack of feedback) stimulating multiplication (hyperplasia) and volume (hypertrophy) of follicular cells
Why is island goiter more frequent in animals?
in coastal area, the air, vegetation and marine organisms are a good source of iodine
What is hyperthyroidism?
over-production of thyroid hormones
What are some effects of hyperthyroidism?
big appetite associated with weight loss, excitable and nervous, heart rate, respiration, digestive passage all increase
What is the treatment for hyperthyroidism?
surgery, radioactive I2 to destroy follicular cells
Where are the adrenals located?
paired organs capping the kidneys
What is the adrenal gland made of?
2 layers, outer cortex (derived from mesoderm) and inner medulla (derived from neural crest)
What is the medulla a part of?
the ANS, equivalent to a ganglion, but with postganglionic cells secreting catecholamines that diffuse in the blood
What are the three zones of the adrenal glands?
zona glomerulosa - secretes mineralcorticoids
zona fasciculata - secretes glucocorticoids
zona reticularis - secretes androgens
How much of the cortex makes up the adrenal glands total mass?
90%
What types of hormones does the adrenal cortex produce?
cortex produces steroid hormones required for survival
How are hormones produced in the adrenal cortex?
stepwise conversion of cholesterol previously absorbed from blood lipoproteins, cytochrome P450 are major enzymes in conversion, cells from each zone of the cortex have different enzymes -> formation of different hormones
Where are mineralocorticoids produced?
zona glomerulosa
After diffusion, where are mineralocorticoids circulated?
circilate loosely bound to cortisol binding globulin (CBG)
What is synthesis and secretion of mineralocorticoids stimulated by?
angiotensin and by direct action of K+ concentration on cortical cells
Does ACTH from pit have impact on aldosterone production?
no, very minimal
What is the function of mineralocorticoids?
regulate metabolism of important inorganic ions, stimulate the reabsorption of Na+ and the secretion of K+ in the distal kidney tubules and collecting ducts, in target cells, adlsoterone binds to its receptor to modulate gene txn -> increase in Na+ K+ pumps in basolateral membrane and increases na+ channels in apical membrane
What do glucocorticoids do?
regulate glucose metabolism, cortisol is the most potent, corticosterone has weaker activity
After diffusing in blood, where does cortisol bind to?
CBG
What happens to free cortisol in the blood?
free hormone portion enters target cells, binds to its receptor and stimulates or inhibits gene txn
What are some target cells of glucocorticoids?
all cells are potential targets
What is permissive action?
activates txn of several enzymes that facilitate the action of other hormones
How does cortisol cause stress?
levels of cortisol increase during stress, it enhances the effect of norepinephrine on blood pressyre, it stimulates gluconeogenesis and inhibits tissue glucose itlisation -> increases plasma glucose concentration, at high level stimulates the degradation of fat and protein -> increases plasma AA and FA concentrations, cortisol inhibits gene txn in many tissues, combined with degradation of fat and protein -> growth inhibition effect, energy conserved for survival during high stress
What are the anti-inflammatory effects of cortisol?
inhibits formation of prostaglandins and cytokines reduces number of lymphocytes migration
How does the hypothalamus respond to internal and external stimuli for glucocorticoids?
hypothalamus responds by releasing ACTH-RH, ACTH-RH stimulates the release of ACTH by ant pit, ACTH binds to its receptor on cell surface in adrenal cortex and increases intracellular cAMP levels
What does ACTH negative feedback loop back to?
short loop, on hypothalamic ACTH-RH
What does glucocorticoids negative feedback loop back to?
long loop on hypothalamus and pit
What is the glucocorticoid deficiency?
Addisons disease
What is the major cause of addisons disease?
autoimmune disorders that destroy adrenal cortex cells
What are the major effects of Addisons disease?
reduced bp -> dizziness
reduced appetite, sluggish, depression, vomiting
What happens if there is a loss of negative feedback for addisons disease?
measurable increase in ACTH secretion
What is the disease for glucocorticoid overproduction?
cushings disease
What is cushings disease due to?
primarily due to pit and adrenal cortex tumours
What happens in cushings disease when cortisol is continuously high?
dogs eat and drink a lot, lose hair, muscles weaken, anti-insulin effects can lead to diabetes
What are androgens similar to?
similar to testosterone
How do androgens circulate?
partly bound to SHBG and albumin
What is the difference between androgens and testosterone?
much lower potency than testosterone
What is the role of androgens in females vs males?
males: unknown
females: transformed to estrogen in adipose tissue -> only source of estrogen after menopause
What does the adrenal medulla secrete?
catecholamines: epinephrine and norepinephrine
What is the secretion of epinephrine and norepinephrine under control of in the adrenal medulla?
secretion partly under the control of the preganglionic sympathetic nerves that release Ach
How do the preganglionic neurons attached to the adrenal medulla secrete the hormones from the adrenal medulla?
Ach depolarises cells from medulla, induces Ca2+ entry and exocytosis of hormones
How is the adrenal medulla a part of the sympathetic nervous system?
secretes epinephrine and norepinephrine, the effects are slower but last longer than the sympathetic system, normal blood level of catecholamines is too low to exert an action
How do catecholamines take action on target cells?
bind to adrenergic receptors in target cells
What are the two types of adrenergic receptors that catecholamines bind to?
alpha and beta, both G-protein coupled receptors
What is the effect of binding an alpha or beta adrenergic receptor?
alpha -> increases Ca2+
beta -> increases cAMP
Where are alpha and beta receptors present?
alpha receptors most common in target cells from sympathetic
beta1 receptors present in heart - increase rate and contractility
beta2 receptors present in muscles from bronchioles -> inhibition of contraction
What happens if alpha receptors are stimulated in arterioles of GI tract?
constriction of smooth muscle
In arterioles of skeletal muscles, what does epinephrine do?
has a dual effect on alpha and beta receptors, low levels activate beta receptors (relaxation) whereas high levels activate alpha receptors (small contraction)
What is stress?
factors that alter or might alter the body internal environment
What are some external/internal contributors/causes of stress?
external: cold, exercise, injury
internal: pain, psychological factors
What is the bodies response to stress?
- direct action of sympathetic system or innervated organs
- indirect action by stimulating release of catecholamines
- increases cortisol secretion via action on ACTH-RH and ACTH
- increased alertness, high hr/bp, increased blood glucose, increased hormone secretion (thyroid)
