Endocrinology

Functions of the endocrine system

regulates physiological processes over a long period of time

Regulatory effects of the endocrine system

nutrient metabolism (water and electrolyte balance to maintain internal environment)

adaptive changes in response to environmental stress

promote smooth growth and development

control reproduction

regulation of red blood cell production

control and integrate activites of the circulatory system and digestive system with the ANS

Exocrine gland

secrete stuff through ducts to the outside of the body (like sweat)

Endocrine gland

lack ducts, release their secretory products- hormones- in to the blood

tropic hormones

hormones whose primary function is the regulation of hormone secretion by another endocrine gland and maintain structural integrity of its target endocrine gland

hydrophilic hormones

water soluable

peptides and proteins

and amines

example is insulin

hydrophobic hormones

lipid soluble

thyroid hormones

steroid hormones derived from cholesterol

ex- cortisol and sex hormones

Hydrophilic synthesis, storage, release, and transport

preproxhormones precursor are synthesized by ribosomes on ER which pinch off the smooth ER in enclosed transport vesicles to the golgi

from er to golgi they are pruned to activate hormones

golgi packs them in secretory vesicles that are stored in the cytoplasm

when stimulated, secretory vesicles fuse with the membrane and hormones exit the cells vis excytosis

transport- dissolves in blood

Hydrophobic synthesis, storage, release, and transport 

cholesterol is precursor for all steroids

enzymatic reactions modify the cholesterol molecule

once formed, the hormone diffuses across the membrane (no storage)

can undergo more changes within blood or other organs

transport- travel through blood on plasma proteins

Mechanisms of hormone action- hydrophilic

bind to surface of target cells and activate second messenger systems (cAMP and Ca2+) to alter the activity of pre-exisiting hormones

Mechanisms of hormone action- hydrophobic

hormone enters cell and activates receptor to activate specific DNA genes (hormone response element) to synthesize the desired protein for the desired effect

ATP

Immediate source of energy for MOST energy requiring cellular processes

However- little ATP stored in cells

Consequently- cells must constantly synthesize ATP

First Law of thermodynamics

total energy won’t change- just converted from one unusable energy source to a useable one

Second Law of thermodynamics

system move from order to disorder - energy is lost as heat

Metabolism

sum total of biomolecule inter-conversions to form ATP

Biomolecules of ATP synthesis

Carbohydrates- glycogen (storage form) + glucose (1 ATP use)

Fatty Acids

Carbohydrate conversion to ATP

Anerobically- converted to lactic acid and ATP in glycolysis

Aerobically- converted to ATP and CO2 in the Kreb’s cycle and ETC

Fatty acid conversion to ATP

ONLY aerobically converted to CO2 and ATP in Beta oxidation

Gluconeogensis

Pyruvate to glucose-6-phosphate to Glucose only in the liver- anabolic

Glycolysis

Glucose → glucose-6-phosphate - catabolic

Glycogenolysis

glycogen → glucose-6-phospahte - catabolic

Glycogen synthesis

glucose-6-phospahte → glycogen - anabolic

Fatty acid synthesis

Acetyl CoA → Fatty acids - anabolic

Beta oxidation

Fatty acids → Acetyl CoA - catabolic

TG synthesis

fatty acids + glycerol → TG - anabolic

Lipolysis

TG → FA + glycerol - catabolic

Animals require constant…

fuel molecules supply for ATP synthesis. between meal storage fuels are used

Storage biomolecules

Glycogen- 1800 kcal of storage, mostly in glycolytic muscle fibers and liver cells

triglycerides- 140,000 kcal of storage, most in adipose tissue- 50% subcutaneous + 50% around visceral organs

proteins- 40,000 kcal of storage, most do other things so they are a last resort

Absorptive phase- after meal, gut is full and glucose is used for energy

metabolic needs- supported by ingested biomolecules

calorie intake > calorie utilization

Net result= left of molecules used for building fuel stores, anabolism (not gluconeogensis)

Fasting phase- time between meals, gut is empty and glycogen is used for energy

metabolic needs- supported by fuel stores

calorie intake < calorie utilization 

Net result= break down fuel stores into intermediate into intermediate forms, catabolism

Anabolism

building large biomolecules from organic subunits

Catabolism

break down large energy rich molecules for energy

Anaerobic carb untilzation for ATP

In fasting- break down glycogen

Aerobic carb untilzation for ATP- absorptive

glucose from gut converted to ATP

Aerobic carb untilzation for ATP- fasting

use glycogen in liver to make glucose for the brain

Aerobic TG untilzation for ATP

FA to acetyl CoA and glycerol to pyruvate to make ATP

Fuel utilization- gluconeogenesis

makes new glucose in the liver primarily for the brain in the fasting state in the liver

2 pyruvate = 1 glucose

Pyruvate from AA, lactic acid, glycerol,

Glycogen makes glucose-6-phosphate

Make fuel storage- FA synthesis

Making FA from acetyl CoA which comes from glucose and amino acids

Carbs to lipids

Glucose → pyruvate → acetyl CoA → FA → TG

Amino acids to carbs

AA → pyruvate → glucose-6-phosphate → glucose

Amino acids to lipids

AA → pyruvate → acetyl CoA → FA → triglycerides

lipids to carbs

X TG → FA → acetyl CoA → X Pyruvate

Yes TG → glycerol → pyruvate

Metabolic capabilities of CNS

synthesize ATP via aerobic carbs, little glycogen stores, dependent on O2 and glucose

Metabolic capabilities of skeletal muscle

40% body weight, metabolic demand varies, synthesize ATP via aerobic and anaerobic carbs + aerobic FA, rich in proteins (can uptake or release AA), large glycogen stores for ATP synthesis

Metabolic capabilities of adipose tissue

Primary function is triglyceride storage, can uptake or release FA depending on need

Metabolic capabilities of liver

site of gluconeoenesis and FA synthesis, can uptake or release glucose depending on need, large glycogen stores to make glucose for the brain

Pancreas endocrine and exocrine function

exocrine- via a duct, release Na+ bicarb and digestive enzymes into lumen of the gut- 98% of pancreas function

endocrine- please variety of hormones into the blood stream via islet of Longerhans- 2% of pancreas function

Islet of Longerhans B cells

60% of cells

synthesize and release insulin

Islet of Longerhans a cells

25% of cells

synthesize and release glucagon

Islet of Longerhans S cells

10% of cells

synthesize and release somatosin

Insulin carb metabolism in skeletal muscle

stimulate glucose transport into cells

increase glycogen synthesis and decrease glycogenolysis- storage

promote glucose utilization to synthesize ATP

Insulin protein metabolism in skeletal muscle 

increase AA transport into cells

increase protein synthesize + decrease protein degradation

Insulin carb metabolism in hepatocytes (liver cells)

stimulate glucose transport into cells

increase glycogen synthesis and decrease glycogenolysis- storage 

decrease gluconeogensis and increase conversion of glucose to FA

Insulin effect on adipocytes (fat cells)

increase lipoprotein lipase activity = increase FA transport into adipose cells

increase transport of glucose into cells- makes glucose-6-PO4 which is backbone of TG

increase TG synthesis and decrease lipolysis

Overall insulin effects

Increase glucose transport into muscle, liver, and fat cells = decrease blood glucose

increase AA into skeletal muscle = decrease blood AA

it is an anabolic hormone

shifts metabolic dependance away from FA to glucose

insulin stimulates glucose transport into cells

insulin binds to insulin receptors on skeletal muscle and adipose tissue

this activates a 2nd messenger signaling cascade in the cell → moves GLUT-4 to the membrane

increases transport of glucose into muscle and adipose cells (10-30x)

* there is always a gradient in because glucose is immediately converted to glucose-6-PO4 to trap it

regulation of insulin secretion

primary= increase BG stimulates B islet cells to release insulin

amino acid increase = increase insulin release

sympathetic activity = decrease insulin release (don’t need to store in flight/fight)

parasympathetic activity = increase insulin release (after eating)

3 cells not dependent on insulin for glucose uptake

brain- always allowed in through GLUT-2

liver- however, insulin enhances glucose metabolism by stimulating first step in metabolism (glucose-6-PO4 conversion)

working muscles- contraction = GLUT-4 insertion for glucose uptake

Glucagon effect on liver

increase glycogenolysis and decrease glycogen synthesis

increase glucneogensis

Glucagon overall effect

increase glucose in blood

regulation of glucagon secretion

primary- increase blood glucose = increase glucagon secretion

secondary- ANS

* sympathetic- increase glucogon secretion (body needs it for ATP)
* parasympathetic- decrease glycogen secretion (have enough blood glucose after eating)

tertiary- amino acids increase = increase glucogon secretion (low aa means low BG)

Skeletal muscle in absorptive state

high insulin low glucogon

increase glucose uptake

increase glycogen synthesis- decrease glycogenolysis

increase glucose utilization - decrease FA utilization

Liver in absorptive state 

high insulin low glucogon 

increase glucose uptake

increase glycogen synthesis - decrease glycogenolysis

increase FA synthesis

decrease gluconeogensis

Adipose tissue in absorptive state

high insulin low glucogon 

increase glucose uptake

increase glycerol synthesis

increase FA uptake (via lioproteinlysis)

increase TG synthesis - decrease lipolysis

Skeletal muscle in fasting state

low insulin + high glugogon

decrease glucose uptake

decrease glycogen synthesis

decrease glucose utilization

increase FA utilization

over time:

increase protein degradation + increase AA release

liver in fasting state

decrease glucose uptake

decrease glycogen synthesis

increase glycogenolysis

decrease FA synthesis

increase glycerol + AA + glycogen synthesis = increase glugluconeogenesis

adipose in fasting state

decrease glucose uptake

increase lipolysis

decrease TG synthesis

increase glycerol release

increase FA release

Posterior pituitary neurons and hormones

supraoptic nucleus + para ventricular nucleus

release ADH and oxytocin

Passage of posterior pituitary neuron release

Once synthesized, ADH and oxytocin travel down the neuron’s axon and become stored in the axon terminals in secretory granules until released to the blood stream when activated by action potentials

ADH is released when

increase in ECF osmolarity is detected by osmoreceptors in the hypothalamus which generates action potentials to the axon terminals of posterior pituitary neurons when osmolarity is greater than 300

decrease in MAP= activates sympathetic NS to release EPI which stalemates granular cells to release renin, which increases angiotensin 2, which activates their receptors on ADH neurons in the hypothalamus which sends action potentials to the posterior pituitary to release ADH from the secretory vesicles

ADH target and effects

adds aquaporins to lumen membrane by activating ADH receptors in the DT and CD

increases water reabsorption in the DT and CD, arteriolar constriction - from angiotensin 2 (decreases TPR), decreases urine flow, decreases osmolarity of plasma ECF

Oxytocin release, target and effect - labor and delivery

labor begins which pushes baby into the cervix

stretching of cervix walls activates mechanoreceptors

APs travel along sensory afferent neurons to the SON or PVN to activate them

oxytocin released from posterior pituitary into the blood stream

oxytocin binds to and activates oxytocin receptors on smooth muscle in the uterus to increase uterine contractions

Oxytocin release, target and effect - milk letdown

Infant suckles on nipple which activates mechanoreceptors around nipples

action potentials on sensory afferent neurons sent to the SON or PVN in hypothalamus to release oxytocin from the posterior pituitary into the blood stream

oxytocin stimulates myoepithelial cells in alveoli

smooth muscle in alveoli contracts to release the milk from the ducts (made by milk secreting alveolar epithelial cells) and is delivered through the nipple

anterior pituitary overview

contains 5 distinct cell populations that synthesize ad secrete 6 different peptide hormone. their secretion is controlled in part by the hypothalamus

anterior pituitary neurons

the hypothalamus contains neurosecretory neurons that release hypophysiotropic hormones in endocrine cells

cell bodies are in hypothalamus but hormones are released into a special circular system the hypothalamic hypophyseal portal system (HHPS)

hypothalamic hypophyseal portal system (HHPS)

specialized vascular system between the capillaries in the hypothalamus (blood into Brian) and the capillaries in the anterior pituitary (blood to body)

transports hormones released by the neurosecretory neurons in the hypothalamus to the anterior pituitary

Endocrine cells of the anterior pituitary

synthesize, store, and secrete anterior pituitary hormones when stimulated by hypophysiotropic hormones that were released by the neuron secretory hormones and entered the capillaries in the hypothalamus, trailed down the HHPS, and entered the anterior pituitary capillaries

hypophysiotropic hormones regulate

the release of anterior pituitary hormones

hypothalamic-pituirary-adrenal axis

Hypothalamus → CRH → anterior pituitary → ACTH → adrenal gland → cortisol → most cells

hypothalamic-pituirary-thyroid axis

hypothalamus → TRH → anterior pituitary → TSH → thyroid gland → thyroxine → most cells

hypothalamic-pituirary-liver axis

hypothalamus → GHRH → anterior pituitary → growth hormone → liver → somatomedians → most cells

Growth hormone growth effects in adolescence

stimulate growth of long bones

promote a proportional increase in soft tissue mass

Growth hormone growth promoting effects - long bone growth

achieved through cell proliferation and maturations


1. IGF-1 stimulates chondrocyte hyperplasie (cell division) in epiphyseal plate
2. conrondrocytes grow (hypertrophy), stretching the plate and pushing the epiphysis away from the diaphysis
3. mature chondrocytes trapped in calcified extracellular matrix from osteocytes (bone cells) and die
4. dead cnodrocytes are cleared by osteoclasts in the diaphysis
5. osteoblasts deposit osteoid matrix in hollowed out region of new diaphysis region

continues until pate is fully ossified which stimulates the end of adolescence growth

Chondrocytes produce

collagen/glycoprotein matrix

Epiphysis

flaring articulated (covered in cartilage) ends of long bone

Epiphyseal plate

layer of cartilage, separates epiphysis and diaphysis, site of IGF-1 action

Diaphysis

uniform cylindrical shaft of long bones

Growth hormone growth promoting effects - stimulate cell division

in most other cells, IGF-1 stimulates cell division (promotes increase in soft tissue mass that accompanies increase in long bones)

Growth hormone growth promoting effects - stimulate sell growth

in most other cells, IGF-1 promotes and increase in cells size (promotes increase in soft tissue mass that accompanies increase in long bones)

Growth hormones metabolic effects - proteins

IGF-1 increases protein synthesis + AA uptake, and decreases protein breakdown

Growth hormones metabolic effects - lipids

GH increases lipolysis and FA in blood, and decreases TG synthesis

Growth hormones metabolic effects - carbohydrates in liver

GH increase gluconeogenisis and glycogenolysis = increases blood glucose

Growth hormones metabolic effects - carbohydrates in other

GH increases FA utilization because of the increase of FA in blood

Growth hormone overall metabolic effect

increases FA in blood, increases glucose in blood for brain, decreases AA in blood

shift metabolic dependance away from glucose to FA

Regulation of GH secretion - diurnal rhythm

daytime- rate of GH release is low and constant

sleep- 1 hr after sleep increases 5 times

Regulation of GH secretion - negative feedback loop

increase in GH = inhibits GHRH release and stimulates GHIH release to decrease GH

Increase in IGF-1 = inhibits GHRH release and stimulates GHIH release and inhibits GH release from the anterior pituitary to decrease GH and IGF-1 release

Thyroid gland anatomy

2 lobes of endocrine tissue joined a a narrow middle called isthmus

Follicular cells of thyroid gland

major secretory cells

arranged in hollow sheered called a follicle functional unit that has an enclosed lumen filled with colloid made of a large glycoprotein called thyrogobulin

They produce 2 iodine containing hormones called teraiodothyroine (T4) and tri-iodothyronine (T3)

Synthesis, storage, and secretion of thyroid hormones

1. thryogobulin is produced by the ER-Gogli complex in follicular cells where it is combined with tyrosine and put in colloid via exocytosis
2. Thyroid capture iodide (iodide from diet) and is transported into follicular cells via the iodide trap (symporter given by Na+ gradient from Na/K+ pump)
3. In the cell, iodide is converted to active iodide via thyroperoxidase on the luminal membrane then it enters colloid through ion channels on luminal membrane
4. Thyroxidase attaches I+ to tyrosine on the thyroglobulin molecule

Mononiodiotyrosine (MIT) = 1 iodide and di-iosotyrosine (DIT) = 2 iodide
5. MIT + DIT = triiodothyronine and DIT + DIT = tetraiodothyronine
6. They are stored in the colloid on the cell membrane attached to thyroglobulin via pepetide bonds
7. when stimulated- follicular cells internalize a portion of the thyroglobulin-hormone complex and lysosomes whose enzymes split the active hormones and MIT+DIT

Hormones are lipophilic and pass through the outer membrane freely and are transported by thyroxine-binding globulin

Target cells and effects of T3 + T4 - metabolic rate and heat production

increase basal metabolic rate- most important regulator of O2 consumption and energy expenditure, + increase heat production (calorigenic effect)