Endocrinology Flashcards
hormone
- specific chemical secreted by a specific tissue
- chemical substance produced and released by endocrine cells, carried through body in blood and exerts regulatory influence on other cells it reaches through the blood
endocrine control
- slow and broadcast
- must circulate to target tissues and diffuse to effective concentrations within tissues before it can elicit a response
- released hormone into blood
- transported to target site
- brings about a certain effect
once hormone is released into blood…
- it is carried to virtually all cells in the body-> only those that have a receptor molecule for hormone respond
- some hormone signaling alters gene transcription and protein synthesis
half life
- time required for half of a set of recently secreted hormone molecules to be removed
target tissues
express hormone receptor molecules that bind the hormone
- any processing at tissue level
- receptor distribution
- sensitivity of target cell depends on the number of functional receptor molecules that target cell expression for the hormone
endocrine systems best suited for…
- long term resgulatory functions
- such as maintenance of blood sugar, blood osmolarity, reproductive potential… etc.
endocrinology studied by:
1) gland removal/replacement
2) effects from overdose (hypersecretion)
3) isolate and characterize specific molecules
4) spontaneous defects
5) cloning gene
6) detailing receptors/signal transduction
bioassay
measure of a hormone in a living system by measuring its effects on the system
- ex: bioassay for androgens with chick combs
- generate standard curve
- problems: subject to variability and sensitivity
chemical measured
HPLC, gas chromatography, mass spec
immunological measure
- RIA (Radioimmunoassay)–> develop antibody against hormone, determine percent binding, generate standard curve
- Elise (enzyme linked immunoadsorption assay)
- both very quantitative and sensitive
- Problem: may not be testing only biologically active substances
chemical regulators
- hormones
- neurosecretions (neuro-hormones released from neurosecretory tissue (ex: ADH, epi/NE), neurotransmitters (ex: Acetycholine, epi/NE))
- parahormones (local hormones, cytokines, H+, CO2)
- phytohormones
- cyclic nucleotides, 2nd messengers
- pheremones (released outside animals for communication within species)
- inorganics ex: Ca++
protein mode of action
- surface receptor
- signal transduction
- 2nd messenger
- transduce hormonal signal into response of target cell
steroid
- synthesized from cholesterol
- intracellular receptor
- new mRNA (interacts with target cells DNA to alter gene expression)
- lipid soluble (can diffuse through cell membrane)
- not stockpiled in vesicles prior to secretion-> when cell is stimulated to secrete steroid hormones, they are synthesized on demand and immediately secreted through diffusion through cell membrane
pituitary gland
- hypophysis
- master endocrine gland
- back of the roof of the mouth
- 2 parts: anterior and posterior
posterior pituitary
neural from the hypothalamus
anterior pituitary gland
derived from epidermal cells in the roof of the mouth
- embryologically derived from Rathke’s Pouch
- non neuronal endocrine tissue
adenohypophysis
- anterior lobe
- intermediate lobe
neurophypopysis
- intermediate lobe
- posterior lobe
median eminance
- forms part of the floor of the hypothalamus
- blood system to the anterior pituitary
anterior pituitary hormone
- STH (somatotropic hormone); growth hormone (influences growth and metabolism)
- TSH (thyroid stimulating hormone)-> supports and maintains tissues of thyroid gland and stimulates the gland to secrete thyroid hormone
- ACTH (adrenal corticotropic hormone)
- Gonadotropic hormones (Gntps)-> FSH (follicle stimulating hormone) and LH(lutenizing hormone)
- prolactin
- lipotropin, endorphins, enkephalins
intermediate lobe hormone
- produces one hormone
- MSH: melanophore stimulating hormone
posterior pituitary hormones
- ADH (antidiuretic hormone)-> vasopressin and vasotocin: limits production of urine and stimulates constriction of arterioles
- oxytocin: causes contraction of uterus during birth and ejection of milk by mammary glands
when neurosecretory cells are stimulated by neurons in brain they…
generate action potentials that propagate from hypothalamus to axon terminal in pars nervosa-> release hormone by exocytosis-> hormone diffuses into blood
hypothalamo-hypophysial portal system
- provides interface between brain and endocrine system
- blood system from the median eminence to the anterior pituitary
- hormones secretes by the hypothalamus are released into median eminence and carried via the protal system to the anterior pituitary
releasing hormones
- stimulate secretion of anterior pituitary hormone
- activate the anterior pituitary to synthesize and release a certain hormone
- mostly small polypeptides
hypothalamus master organ regulates anterior and posterior pituitary
- via releasing hormones (anterior pituitary)
- via neural input (ADH, oxytocin), produced in hypothalamus, stored in posterior pituitary gland
CRH
- corticotropin releasing hormone
- releases ACTH
GH-RF
- growth hormone releasing factor
GH-IRF
- growth hormone inibitory releasing factor
- growth hormone inhibited from being released by negative feedback
TRH
- thyrotropin releasing hormone
- releases TSH
- TSH stimulates release of TH from thyroid glands
GNRH
- gonadotropin releasing hormone
- releases FSH/LH
Prl RF
- prolactin releasing factor
- releases prolactin
- probably dopamine
PIRF
- prolactin inhibitory releasing factor
- inhibits prolactin
MSH-RF
releases MSH
MSH-IRF
inhibits MSH
control of anterior pituitary hormones
- via feedback systems
- ex: TSH
- inc cold-> hypothalamus (TRH_ to ant pit (TSH)-> thyroid gland-> TH-> inc MR, inc heat
- with negative feedback to ant pit and hypothalamus
- can interpret change in environmental conditions and respond
- hypothalamus picks up into from brain and responds accordingly
negative feedback
- hormone causes changes in its control pathway that suppress its own secretion (stabilizes blood concentration of hormone)
growth hormone
- produced by somatotrophin
- half life: 20-30 minutes
control of GH
- growth hormone, thyroid hormone, and androgens work synergistically (enhance each others effects) in the growth of young animals
- via GH-RF and GH-IRF
1) dec blood glucose: hypoglycemia-> inc GH release; also inc insulin levels-> inc GH-RF
2) increased amino acids-> inc GH
3) stress: glucocorticoids released during stress response inhibit secretion of GH from ant pit
GH effects on growth
1) bone growth: GH simulates the liver, kidney to produce somatomedin
somatomedin
- responsible for skeletal effects
- stimulates epiphyses (long-bone) endplate growth
- to lay down bone at the end of the shaft os long bones
GH effects on metabolism
1) inc lipid utilization and mobilization-> inc FFA-> energy source
2) Protein anabolic effects (causes synthesis of proteins(stimulates translation), inc AA uptake)
3) Carbohydrates
GH and carbohydrates
- inc blood glucose
- stimulates gluconeogenesis (producing glucose via AA and lipids; reverse of glycolysis; fatty acid-> glucose production)
- also depresses glycolysis (breakdown of glycogen); so conserves glycogen stores
synergistic
one hormone amplifies affect of another
GH synergistic with horomone
1) Thyroid hormone (GH is more effective with TH; also TH is needed for normal secretion of GH)
2) ACTH-> inc adrenal size
3) sex steroids-> inc size of accessory reproductive organs
Panhypopituitarism
- insufficient secretion of pituitary hormones
- GH, TSH, ACTH, GNTP… all anterior pituitary hormones are secreted at low amounts
- not proper growth of long bones
- no GNTP-> no sexual maturity
hyposecretion of only GH
sexually mature, but dwarfs
GH is in proper levels but somatomedin is low
- metabolic effects aren’t mediated by somatomedin so these are normal
African pigmies
- GH and somatomedin are normal, but tissues won’t respond
- ex: binding sites are not there (generates dwarfism)
hyposecretion of TH
- cretinism
- mental disorder
- nothing to do with GH, but growth is also limited
hypersecretion of GH
gigantism
thyroid
- thyroid gland is hooked to the trachea on either side, bilobed
- arranged in follicles: layer of secretory epithelia surrounded by and open space-> colloid
- in lower vert, the thyroid tissue isn’t compacted into 1 gland, its scattered
- thyroid tissue made up of a number of follicles containing a single layer of cells, surrounding an open space: colloid witch is filled with proteinaceous material
thyroglobulin
- large protein
- fluid in this follicle space contains thyroglobulin where TH is bound to until secreted
- TH is synthesized and bound to thyroglobulin at the apical surface between secretory epithelium and lumen of colloid
- T3-T4 is stores in colloid
- when needed: retrieval by endocytosis and T3 and T4 cleaved and released into the blood
synthesis of TH
1) active uptake of I- (iodide) from the interfollicular region into the secretion cells
2) basic structural unit-> AA tyrosine with iodine
- secretory cell synthesizes thyroglobulin
iodine
- iodine is an essential nutrient for vertebrate animals because thyroid hormone includes atoms of iodine in its chemical structure
- tyrosine residues become iodinated on the thyroglobulin
- with one I= 3 monoiodotyrosine (MIT)
- with two I= diiodotyrosine (DIT)
- couping: DIT + DIT-> T4 thyroxine *form of TH); removal of one iodine or MIT-> T3 (more active; conversion occurs at target cell)
thyroid hormones
- T4 and T3
- in the blood: small hormones, easily filtered through the kidney
- usually bound to large proteins, albumins and globulins in the blood transport them (specifically TBG= thyroid binding globulin)
- only T3 and T4 are active
- T3 has greater activity than T4 at the cell level
- at the cell level: T4-> T3
- TH has a very long half life (couple of days)
control of TH synthesis
- TSH stimulates (from ant pit)
A) I- uptake
B) iodination of tyrosine
C) stimulates proteolytic enzymes which cleave T4 from thyroglobin
D) stimulates proliferation of follicular cell growth and number - via cAMP
control of TSH release
- TRH from hypothalamus
- negative feedback of TH (at hypothalamus and anterior pituitary)
- cold will stimulate TRH
- large mean
- possibly also low blood glucose-> GH and TSH
permissive
presence of one hormone is required for the other hormone to exert its full effect on target tissue
metabolic effects of TH
- inc Basal metabolic rates (BMR)
- assessed via O2 consumption (inc oxygen consumption)
- calorigenic action of TH (generates heat)
- inc O2 consumption- oxidative phosphorylation process for O2 uptake and energy production (more heat produced during this)
thyroid hormone effects on non shivering thermogenesis
- in birds and mammals for heat production
- via activating ATPases; dec in ATP-> net outcome an inc in MR and inc heat production
- normal cell gradients: within cell high K+/low Na+; outside cell opposite
- active transport will use ATP for these pumps (ions will correct action of pump via moving down gradients, so process is ultimately producing heat and not affecting gradient)
TH affects metabolic processes via…
- oxidative phosphorylation and active transport pumps
- active transport pumps increased activity
- inc new mRNA for ATPase
effect of TH on carbohydrate metabolism
effect on glucose
- inc glucose uptake across the intestine
- inc glycogenolysis (breakdown of glycogen)
- TH stimulates use of glucose by cells via increase MR (dec blood glucose)
- net effect overall= inc in blood glucose even though glucose is used when MR is inc
TH effect on lipids
dec cholesterol levels
TH effect on growth and development
- effect on proteins: protein anabolic hormone
- promote protein synthesis and associated growth
- synergistic with GH
- need combo of TH and GH for proper growth
- all vertebrates need TH for growth and differentiation (esp for gonadal development and neural development)
- with cretinism- no TH present myelin sheath on nerves doesn’t develop-> mental retardation, deafness, defects of muscular coordination
hypothyroidism
problem with body temp regulation (harder to warm up, especially along extremities)
- TH inc concentration of nerve growth factor
- needed for dendritogenesis and regeneration of sympathetic neurons
effects of TH on amphibian development
- TH necessary for metamorphosis
- tadpole in H20 environment *gills/tail)-> adult in land based (lungs)
- hyposecretion or no TH-> no adult, large tadpole
- young tadpoles-> inject TH-> small frogs
- a number of physiological and morphological changes associated with metamorphosis
- associated with development of median eminence in hypothalamus (promotes triggering of ant pit hormone (TSH) via TRH)
juvenizing hormone
- prolactin has a juvenizing effect
- inhibit metamorphosis
- PRL-IRF (dopamine) is released to dec prolactin levels so metamorphosis can take place
- TH promotes the development of median eminence i hypothalamus-> allows releasing factors-> ant pit-> inc TSH-> TH
- build up of TH puts metamorphic changes in sequence
cardiac output and TH
- TH stimulates cardiac output by increasing HR and force of contraction
- inc TH-> inc body temp-> heat dissipation mechanism-> peripheral vasodilation-> dec BP-> stimulates CO
TH effect on H2O and solute balance
- attributed to inc in GFR due to inc CO
- in fish: TH is key to osomoregulation (active transport of ions across gills
- stimulation of Na+/K+ pumps and Cl- cells
TH effects on integument
- low TH-> yields deficiency in hair growth, feathers
TH effect on adult mammals
- TH in concert with prolactin
- regulation memmary gland development
- TH needed for ductal system of mammary gland
hyposecretion of TH
- goiter results of I- deficiency
- without TH= no neg feedback so inc in TSH-> stimulates thyroid hypertrophy
- myxedema= build up of fluid under skin
- low TH symptoms= low MR, blood sugar, slow reflexes, electrolyte imbalance and poor cold tolerance
goiter
- enlargement of thyroid gland in neck that results when blood concentration of thyroid hormone is too low
- TH exerts neg feedback on neurosecretory cells that secrete TRH (stimulates secretion of TSH by cells in ant pit)
- low iodine= high TRH secretion-> stimulates thyroid gland-> thyroid gland grows bigger over time in low iodine environment
hypersecretion of TH
- Graves disease- thyrotoxicosis
- inc MR, hyperglycemia
- inc in protein catabolism since MR rate high-> generates neg nitrogen balance
- inc in CO= inc BP and GFR
- jittery
comparative viewpoint of TH
- homeotherms= TH role calorogenic= inc in MR and body temp
- lower vert and homeotherms= development, growth effects, and osmoregulatory
insulin
hormone involved in managing glucose in short-term fluctuations of nutrient availability
- favors storage of nutrients-> uptake of glucose, fatty acids, and amino acids
balance glucose in blood
- insulin from beta cells in pancreas promotes uptake of glucose from blood
- glucagon is secreted by alpha cells and opposes action of insulin (stimulates release of glucose and fatty acids in blood)
pancreatic tissue with endocrine function
- islets of langerhans
- own vascularization
- alpha, D, F, and beta cells-> all products released into blood
beta cells
produce insulin
- during digestion (inc concentration of glucose and AA in blood), beta cells secrete insulin
D cells
produce somatostatin (growth hormone inhibitory releasing hormone)
alpha cells
produce glucagons
F cells
produce pancreatic polypeptide
insulin from beta cells and glucagon from alpha cells are…
- antagonistic hormones
- concerned with storage versus utilization of glucose
- with inc in blood glucose= inc insulin, dec glucagon
- with dec blood glucose= dec in insulin, increase in glucagon
dec insulin concentration in blood=
shift to mobilization of nutrients from stores (breakdown of glycogen and lipids)
negative feedback
hypoglycemic factor
- insulin is the only hypoglycemic factor
- increase glucose uptake by cells, decrease blood glucose
hyperglycemic factor
- glucagon
glucagon and GH
- stimulate release od insulin
1) directly act on beta cells
2) increase blood glucose
GH and glucocorticoids
- GH and glucocorticoids act synergistically with epi to enhance epi’s effect on lipid breakdown
- background levels of glucocorticoids are essential to preventing levels of blood glucose from plummeting during fasting/stressors
glucocorticoids
stimulate glucose fromation and are required for glucagon and epinephrine to exert their effects
insulin is a product of…
proinsulin= alpha chain= 1-21 residues
- beta chain= 30 residues
- connecting peptides- residues 31-63
proinsulin precursor
- pre-proinsulin
- “pre” gets cleaved off before pro-insulin folds onto itself
synthesis of proinsulin
- occurs on rough ER-> transferred to golgi-> by 60 min, insulin granules associated with microtubules
primary effects of insulin
1) cause cell uptake of glucose
- inc cellular uptake of glucose by most tissues (neural tissue is an exception)
- inc permeability of cell to glucose
- facilitates co-transport of glucose into cell
- dec blood glucose
2) inhibits lipase enzymes in adipose tissue (inhibits breakdown of lipids): dec lipid mobilization, secondary effect: imc lipogenesis due to glucose in cell
3) insulin stimulates amino acid uptake in cells-> stimulating protein synthesis (will inhibit gluconeogenesis by AA
4) insulin increases K+ uptake
secondary effects once glucose is within cells
- insulin stimulates glucose utilization within cell
- increases glycogen synthesis for storage (glycogenesis)
- inc glucose oxidation; ie: phosphorylation and breakdown (glycolysis)
- both use up cell glucose and draws more glucose into cell
insulin studies
- often studied with drug (alloxan) that specifically destroys beta cells
- no insulin production= hyposecretion of insulin= diabetes mellitus
- causes hyperglycemia (results from decreased glucose entry into cell and blood glucose levels high but cell glucose levels low and decreased lipogenesis
how does the cell compensate for low blood glucose
- going to affect carbohydrate and lipid metabolism to promote gluconeogenesis (breakdown of lipids and carbs and protein)
- inc FFA and AA
- excess blood glucose= spills over into urine (glycosuria)= high urine osmolarity= lots of water and ion loss via urine= greater thirst (polydipsia)
diabetes mellitus
- disorder of beta cells or target cells not responsive to insulin
- if it bets cells: insulin dependent diabetes
- if its target cells: non-insulin dependent diabetes
diabetes insipitus
hyposecretion of ADH= high urine production
high blood glucose effects…
- cells like retina, lens of eye, red blood cells, and other neural tissue which don’t rely on insulin for glucose have excess glucose
- glucose metabolized into sorbitol won’t diffuse out-> high cell osmolarity causes excess H2O uptake in these cells and electrolyte problems-> blindness, cataracts, numbness
since cell glucose is low in most cells (diabetes)
it stimulates the need to increase glucose levels= increased gluconeogenesis from metabolism of proteins and lipids= protein catabolism
effects of protein catabolism
- generates negative nitrate balance
- N2 being excreted and AA breakdown faster than synthesis
- insulin uptake of AA is removed
effects on lipids (diabetes)
- effects lipids via increased lipase-> inc FFA froms ketone bodies-> dec pH-> metabolic acidosis-> attempt to correct via inc respiration rates
effect on K+ (diabetes)
- without insulin, blood K+ is high but cell K+ is low (K+ stores lost in urine)
vascular and cardiac problems caused by low insulin
increased water loss at kidney= dec BP= triggers systems to inc CO
respiration effects (diabetes)
from metabolic acidosis: ins RR= inc CO2 loss
renal effects (diabetes)
dec H2O retention, high K+ loss
juvenile diabetes
Type I= hyposecretion of insulin= defect beta cells
maturity onset diabetes
- Type II
- middle age people tissues aren’t receptive to insulin
insulin mode of action
- through surface receptor and tyrosine kinase
- receptor has 2 alpha and 2 beta chain bonded by a disulfide bridge subunits
hypersecretion of insulin
(Insulin shock)-> hypoglycemia
- normal remedy is to eat more often
- major effect of hypersecretion of insulin is on neural tissue since it doesn’t store glycogen
- low blood glucose will cause dizziness
glucagon
- works with insulin to ensure stable levels of glucose in blood
- hyperglycemic effect
- released from alpha cells of pancreas
- related structurally to secretin, GIP, and VIP
- can also be produced by some cells along GI tract
- main stimuli for release= low levels of glucose in blood
- glucagon inc production of glucose and its release into blood
- inhibits lipid synthesis and stimulates adipose cells to break down triacylglycerides into FAs and glycerol and release into blood
glucagon stimulates…
- inc in blood glucose
- stimulates hepatic(Liver breaks down glycogen and releases glucose into blood)) production and secretion of glucose
through glycogenolysis and gluconeogenesis (new glucose formed from non carb sources) - stimulates ketone bodies from fatty acids (ketogenesis)
- as BG levels rise, glucagon secretion dec by negative feedback
insulin-glucagon relations on a daily basis
- levels of each depend on diet
- with food consumption= stimulates insulin release= promotes glucose uptake and storage= dec blood glucose= stimulates glucagon release= glycogenolysis= inc blood glucose
- stomach has stretch reflex which will stimulate insulin release
- some GI hormones will trigger insulin release
high protein diet
- trigger more glucagon release
- after high protein meal, both insulin and glucagon rise
- rise of insulin promotes incorporation of absorbed AA into body proteins
- inc glucagon because high protein provides little glucose-> ensures glucose output from liver glycogen stores even in high insulin levels
sensitivity to insulin or glucagon will depend on diet
- carnivores are typically more sensitive to insulin (need to store carbs and protein)
- herbivores typically more sensitive to glucagon (use other things besides glucose as a carbon source)
- birds and reptiles more sensitive to glucagon than insulin
- amphibians are more sensitive to insulin
- invertebrates have hypoglycemic and hyperglycemic factors
hormone that dec blood glucose
insulin
hormone that inc blood glucose
glucagon, epi, thyroid hormone, glucocorticoids, GH
epinephrine and BG
- epinephrine stimulates alpha cells to secrete glucagon and inhibits beta cells from secreting insulin
