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Berthold's study
- first formal study of endocrinology
- roosters, usually mate w hens, attack other roosters, crow, larger and distinctive look
- capons (castrated prior to adulthood), no mating w hens, less aggressive, don't crow, smaller
-1849
- tried reimplanting the testes into the abdominal cavity and the male developed normally
- tried transplanting another hens testes and the male developed normally
- concluded that testes are transplantable, transplatable testes can function and produce sperm, testes function is not directed by nerves (bc nerves were cut and didn't regenerate and they were put back in a totally different spot)
- when transplanted they regained access to blood supply, showed that they were a secretory blood-born product coming from the testes
what are hormones
- organic chemical messenger
- released from endocrine cells and glands
- travels through the bloodstream
- any cell receiving blood can potentially receive a hormonal message
- interact w target cells from a distance
- need a receptor, sufficient numbers of those receptors must be present for a hormone to exert any effect
- cause a biological response (activate cellular pathways, gene expression, protein synthesis, etc.)
neural transport
- much shorter distance relative to hormonal
behavior affects hormones and hormones affect behavior
- bidirectional relationship
how can hormones affect behavior
- hormones can make environmental cues more salient
- alter speed of neural processing or high processes like motivation or attention
- might affect the vocal organ, like development
how can behavior affect hormones
- when you lose, testosterone goes down
- when you win, testosterone goes up (physically win/lose or mentally)
- social factors - domincan males during dice tournaments show elevated testosterone only when defeating outsiders, not friends
- observing a competition can cause changes too
- women's testosterone levels increase after sex more than after exercise
- eating and sleeping increase/decrease some hormones
ways to measure hormone levels
- immunassays (radioimmunoessays and enzyme immunoassays)
- imminohisochemistry
- blots
- in situ hybridization
- brain imaging (fMRI)
Radioimmunoassay (RIAa)
- used to measure hormone levels
- uses antibodies and purified radiolabeled ligands
- can measure how much is left after they compete for receptor slots
Enzyme Immunoassay (EIA)
- uses the principle of competitve binding of an antibody to its antigen to determine the presence or quanity of a biological substance such as a hormone
pregnancy test example
- HCG is whats measured
- signals during pregnancy, eps early on
- reacts w antibodies, binds with another antibody, color appears
- control shows that the reaction worked
Immunohistochemistry (IHC)
- uses antibodies to label hormones or receptors in teh brain or other tissues
blots
used to determine whether a specific protein or nucleic acid is present in a tissue sample
- southern blot - DNA
- northern blot - RNA
- western blot - Protein
in situ hybridization
- used to identify cells or tissues producing RNA molecules that encode a specific protein (such as a hormone)
- advantage over blots is that it tells us if a protein is bring produced in that tissue, not just present
- can be quantified
brain imaging (fMRI)
- detects neural activity changes during specific tasks or conditions, aka measures function
- detects changes in the ratio of oxyhemoglobin to deoxyhemoglobin. when brain regions increase activity, there is an increase in oxygenated blood leading to a net increase in signal
ablation and replacement
- ablation: the removal of the suspected source of the hormone
1) a gland beleives to produce a hormone that affects a behavior is surgically removed
2) the effects of that removal are observed
3) the hormone is replaced
4) have the consequences of the ablation been reversed by replacement?
pharmacological techniques
- usually involves introducing a chemical agent that can stimulate or inhibit hormone action
- agonist: binds to the receptor of a hormone and miics the action of that hormone
antagonist: binds to the receptor of a hormone but does not activate it
routes of administration for hormones
- peripherally through injection
- centrally through cannulation
- vein or artery catheterization
- pills, patches, gels, injections
optogenetics
- control over the activity of neurons, can silence or cause them to fire
- engineered microbial opsins that repsond to specific wavelengths of light
- channelrhodopsin-2 (ChR2) - non-specific cation channel, derived from green algae, activated by blue light, excitatory
- Halorhodopsin (NpHR) - chloride pump (moves Cl- into the cell), derived from the halobacterium, activated by yellow light, inhibitory
Genetic Manipulations
- knock out (KO) - engineered so that a specific gene has been deactivated
- transgenic - engineered so that there is an overexpression of a specific gene
- CRISPR/Cas9 - a gene editing tool that alters DNA sequences to modify gene function
endocrinology
the scientific study of the endocrine glands and their associated hormones
intracrine mediation
regulate intracellular events, doesn't leave the cell
autocrine mediation
leaves cell and reenters, feed back to influence the same cell that secreted them
paracrine mediation
cells secrete chemicals that affect adjacent cells
ectocrine mediation
ectocrine substances such as pheromones are released into the environment by individuals to communicate with others
Testosterone example
- leydig cell produced T
- it goes through the bloodstream to muscle tissue (endocrine)
- it goes to sertoli cell, nearby (paracrine)
features of the endocrine system
- endocrine glands or cells are ductless
- endocrine glands have a rich blood supply
- hormones are secreted into the bloodstream
- hormones travel in the blood to virtually every cell
- hormone receptors are specific binding sites embedded in the cell membrane that interact with a particular hormone
endocrine deficiency despite high hormone levels
- occurs when receptors are insufficient or unresponsive
- two causes
1) clinical conditions, genetic mutations in receptors or type II diabetes insulin resistance
2) receptor downregulation due to high hormone concentrations
endocrine excess to elevated receptor numbers
- if target tissues have more receptors than usual, a normal or elevated hormone level can produce exaggerated effects
hypothalamus
control of hormone secretions
pinal gland
reproductive maturation, body rhythms, melatonin production
pituitary gland
anterior pituitary
- hormone secretion by thyroid, adrenal cortex, and gonads
posterior pituitary gland
- water balance, salt balance
thyroid
growth and development, metabolic rate
adrenal glands
adrenal cortex
- salt and carbohydrate metabolism, inflammatory reactions
adrenal medulla
- emotional arousal and stress response
pancreas main purpose
sugar metabolism
gut
digestion and appetite control
gonads
body development, maintenance of reproductive organs in adults
what are the 4 classes of hormones
protein and peptide hormones
steroid hormones
monoamines
other lipid-based hormones (not true hormones)
protein and peptide hormones general
- made of amino acid building blocks
- longer chain: protein hormone
- shorter chain: peptide hormone
- metabolism is reported as biological half-life (time for concentration to reduce by 50%)
what are the types of protein and peptide hormones
- hypothalamic hormones
- pituitary hormones
- thyroid and parathyroid hormones
- pancreatic hormones
- gastrointestinal hormones
hypothalamic hormones
- neurosecretory cells: function as an endocrine gland but similar to conventional neuron
- neurohormones: released by NSCs into blood vessels in the pituitary rather than into a synapse
hypothalamus releasing hormones
thyrotropin-releasing hormone (TRH): stimulates the release of thyroid-stimulating hormone (TSH)
growth hormone-releasing hormone (GHRH): also called somatocrinin, provokes growth hormone release
gonadotropin releasing hormone (GnRH): regulares follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
Corticotropin-releeasing hormone (CRH) - stimulates release of adrenocorticotropic hormone (ACTH)
hypothalamus inhibiting hormones
- somatostatin (GHIH): reduces growth hormone secretion
- gonadotropin-inhibitory hormone (GnIH): inhibits release of GnRH and gonadotropins
other hypothalamic hormones
- dopamine (DA)
- prolactin inhibitory hormone (PIH)
- Hypocretin and orexin: wakefulness and sleep
pituitary general
- grows out of the bottom of the hypothalamus
- hypothalamus controls the anterior pituitary, then the anterior pituitary control the posterior pituitary
anterior pituitary hormones
- derived from the soft tissue of the upper palate
- the anterior pituitary regulates other endocrine glands (master gland)
- protein hormones (called tropic hormones)
- topic hormones affect the secretion of other hormones from their target glands
how does the hypothalamus control the anterior pituitary gland
- the hypophyseal portal system
- axon terminals of hypothalamic neurons release neurohormones near capillaries that give rise to portal vessels
- neurohormones from the portal vessels stimulate or inhibit the release of hormones from anterior pituitary cells
- anterior pituitary hormones leave the gland vis the blood
anterior pituitary hormones
- luteinizing hormone (LH)
- follicle-stimulating hormone (FSH): stimulate steroid hormone production and gamete maturation in the gonads
- thyroid-stimulating hormone (TSH): regulates thyrid
- growth hormone (GH): stimulates somatic growth, regulate production of somatomedins (insulin-like growth factors)
growth hormone
- secreted in pulsatile fashin
- GHRH, SWS, exercise, fasting and stress promote secretion secretion
- IGF-1 mainly liver but also local tissue
anterior pituitary prolaction
- named after role in promoting lactation but also has hundreds of functions known across species
reproduction
growth and development
water and electrolyte balance
maintenance of integumentary structure
NO prolactin-releasing hormone, more general affects
POMC
- POMC (pro-opiomelanocortin) is a precursor protein synthesized in the anterior pituitary, cleaved into the following proteins
- Adrenocorticotropic (ACTH) - stimulates the adrenal glands to secrete corticosteroids
- Melanocyte-stimulating hormone (MSH) - regulates skin color in some vertebrates (as well as sexual function and appetite)
- B-endorphin - endogenous opioid
posterior pituitary hormones general
- neural origin is in the base of the brain
- hypothalamic neurohormones get released into the posterior pituitary
- acts as a reservoir for oxytocin and vasopressin
- 75% volume is from axons
- 25% is made up of glial cells called pituicytes
- provide structure, balance, extracellular fluid, and mediate the secretion of oxytocin and vasopressin
how to think of AP and PP
- AP: production facotory
- PP: storage warehouse
oxytocin
- the love hormone
- released by the PP
- uterine contractions (receptors for it increase around birth)
- milk ejection let down
vasopressin
Also known as antidiuretic hormone (ADH) and Arginine vasopressin (AVP)
controls of the body osmotic balance
high plasma osmolarity - ADH release
acts on receptors in kidneys to increase water reabsorption
also blood pressure regulation
alcohol decreases ADH
thyroid and parathyroid
- high cascularized H shapped organ
- consists of many follicles which produce the thyroid hormones
- needs iodine to function
- stores in large quanities in collids inside follicles
C-cell and parathyroid hormones
- C-cells are endocrine cells in the thyroid that secrete the hormone calcitonin(CT)
- CT lowers blood calcium levels but inhibiting therelease of Ca from the bone
- parathyroid secretes parathyroid hormone (PTH), which increases blood calcium levels and inhibits phosphate resorption from the kidneys
- both CT and PTH are regulated by blood calcium levels with no anterior pituitary involvement
pancreas in general
- exocrine and endocrine functions
- endocrine tissue is called the islets of Langerhans
- Innervated by the vagus nerve, stimulates insulin release
pancreatic hormones
b cells produce insulin
- highly concerved
- only hormone to reduce blood sugar levels
- receptors found throughout the body and brain
- take blood glucose into cell or store in muscle as glycogen
a cells produce glucagon
- first acts in the liver to stimulate glycogenolysis (breaking down glycogen into glucose)
-acts in opposition to insulin by increasing blood glucose levels
delta cells release somatostatin
- inhibits release of insulin and glucagon locally
PP/F cells release pancreatic polypeptides
- released by protein, fasting, exercise, hypoglycemia
- PP treatment suppressed appetite and food intake
- may modulate exocrine secretions
e cells release ghrelin
- released from stomach
- stimulates appetite
gastrointestinal hormones general
- secretin, cholecystokinin (CCK), and ghrelin
- goals:
coordinate digestion and absorption
regulate gastric emptying and motility
signal nutrient arrival to the pancreas and brain
secretin
- discovered by william bayliss and ernest sterling
- denervated jejunum loop in dogs, when perfused with acid there were secretions from the pancreas and when acid was added to the blood there were no secretions
- proved that when acidic food enters from the stomach, duodenal mucous cells release secretin which travel to the pancreas and release biocarbonate from exocrine cells
- also stimulates peptin release, insulin release, renal function and inhibits GI tract movement
CCk
- release of digestive enzymes from the pancreatic exocrine cells
- contraction of gallbladder and release of bile
ghrelin
- peptide made in endocrine cells in the stomach
- stimulates release of GHRH
- treated mice show increase food intake and fat deposition
- humans ate 30% more after ghrelin treatment
- levels peak before food intake
glucagon-like peptide-1
- peptide made in endocrine cells in the intestines
- stimulates release of insulin
- decreases glucagon release
- slows gastric empyting
- increases satiety
gonadal functions
- produce gametes
- production of hormones
testes
- seminiferous tubules: where sperm is made
- sertoli cells have heads of nearly mature sperm embedded for nourishment and produce inhibin and activin
- leydig cells produce steriod hormones
ovaries
- follicles, each one contains a developing ovum
- theca cells produce steroid hormones
- grunulose cells - produce inhibin and activin
- corpus luteum: endocrine structure that forms from the remnants of an ovarion follicle following ovulation, secretes progestin and relaxin
- stroma: connective tissue
gonadal hormones
- mullerian inhibitory hormone (testes): inhibits the mullerian duct system which gives ruse to female accessory sex organs
- inhibin (ovaries and testes): feeds back to block FSH release from anterior pituitary and inhibit aromatase
- activin (ovaries and testes): stimulates FSH release, and stimulates aromatase activity in ovaries
- relaxin: produced by the corpora lutea at the end of pregnancy to relax pelvic ligaments in prep for labor
placental hormones
- temporary endocrine organ maintains respiratory, nutritional function for the fetus
- human chorionic gonadotropin (HCG): placental hormones similar to prolactin and GnRH, some supplemental ones (CC, CT
- chorionic somatomammotropin (CS) initiates onset of maternal behavior
adipokine hormones
leptin
- protein secreted from adipose cells
- induced energy expenditure and inhibits food intake
- blood concentrations increase following eal in concert with insulin release
adiponectin
- peptide secreted from adipose cells
- expression of mRNA is decreased in obese mice and humans
- treatment w adiponectin reduces blood glucose and insulin resistance
steriod hormones
- fat soluble hormones derived from cholesterol
- primarily produced in brain gonads and adrenals
- not stored in cell so it can be hours between signal for production and release
- can't be stored in vesicles
prohormones
- act as a hormone and convert into a different hormone
progestins
- pregnenolone is a progestin and a precurser to all other steroid hormones
- named for their pro-gestational actions in maintaining pregnancy
- in mammals involved in maintaining pregnancy and the initiation and cessation of mating
where are mineralocorticoids produced
zona glomerulosa of adrenal cortex (SALT)
example: aldosterone
where are glucocorticoids produced
Zona fasciculata of the adrenal cortex (SUGAR)
example: cortisol
where are androgens produced
zona reticularis of the adrenal cortex (SEX)
example: DHEA, androstenedione
corticoids
- pregnenolone make sprogesterone makes corticoids
- glucocorticoids are involved in carbohydrate metabolism and stress
- ex: corticosterone - reptiles, birds, some mamals secrete it and mice
- ex: cortisol: primary GC for humans, primates, and bony fish
- mineralocorticoids like aldosterone mediate ion exchange and water metabolism
androgens
- pregnenolone becomes androgens
- androstenedione and DHEA are weak
- testosterone
5a and b-dihydrotestosterone are strong and derived from testosterone
roles for androgens
- speratogenesis
- maintain accessory sex organs
- male secondary sex traits
- morphological effects
- behaviors
- metabolism
- ovarian function, cardiac health, bone metabolism, muscle mass
estrogens
androgens become estrogens
enzyme called aromatase converts androgens to estrogen
ovaries produce androgens
17b estradiol
estriol
estrone
roles for estrogens
initiate formation of corpora lutea
affect the genital tract
mammalian female secondary sex characters
sexual behavior
maternal aggression
water metabolism
calcium metabolism
libido, erectile disfunction, spermatogenesis
neurosteroids
made in both CNS and PNS
predominantly in glial cells
modulate neurotransmitter receptors
adrenal medullary monoamine hormones
- prepare the body for action
- catecholamines, like epinephrine, norepinephrine and dopamine
- stress, exercise, low temps, anxiety, hemorrhage drive release
- increaed HR and cardiac output
- vasoconstriction of arteries and veins
- dilation of skeletal and liver blood vessels
- increased glycolysis
- increased blood glucagon and decreased insulin
- all derived from tyrosine
thyroid hormones pr
- T3: increases basal metabolic rate
- T4: primary hormone secreted from the thyroid
- made from tyrosine
- fat soluble and need a carrier protein to travel through the blood, like a steroid hormone
functions of thyroid hormones
- metabolism: heat production, adapts to changing temps, glucose movement
- growth and differentiation
- reproduction
prostaglandins
- not strictl a hormone, paracrine factor
- found in seminal fluid and cause contraction or relaxation of the uterus
-
receptors for protein/peptide and monoamine hormones
- bind to surface level receptors
- G proteins second messagers
receptors for steroid hormones and thyroid hormones
- can interact w membrane receptors
- diffuse through the membrane
regulation of receptor concentrations
- up regulation: high concentration of hormone increases # of receptors
- down reg opposite
called homospecific priming
heterospecific is when the concentration of one hormone can increase or decrease the number of receptors for a different hormone