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Berthold endocrine experiment
removed testes from chick to see what it would do, led to underdeveloped male rooster; when testes removed and then replaced, fully developed male rooster
Berthold endocrine experiment impact
organ (testes) secrete chemical (testerosterone) which makes changes
four types of experiments in endocrinology- is the molecule sufficiet for an effect
give the hormone and determine its effects; tells us whats possible, may not be physiological
four types of experiments in endocrinology- is the molecule necessary for an effect
block the hormone and determine if physiological response is blocked without the molecule; tells you when you disrupt something changes
four types of experiments in endocrinology- is the molecule made or secreted in response to stimuli
measure the concentration of the molecules in blood or tissue
four types of experiments in endocrinology- what does the molecule look like
what is the sequence or structure of the molecule, where is it made
hormone
chemical messenger that is secreted by cells, travels though blood, and acts on other cells
exocrine secretions
digestive enzynes; excreted outside the body; go through duct
pheromones
secreted outside of the body, don’t get into blood
paracrine signaling molecules
acts on cells nearby the ones that secrete it
autocrine signalling molecules
acts on the same cell that secretes it
intracrine signalling molecule
act within the cell that produces it; doesnt go thru blood
three major classes of hormones
proteins, steroids, modified amino acids
protein subclass
proteins, peptides, glycoproteins
protein hormones hydrophilic or lipophilic
hydrophilic
protein hormone structure/precursor
DNA → RNA → protein
steroid hormones subclass
n/a
steroid hormone hydrophilic or lipophilic
lipophilic
steroid hormone strucutre/precursor
enzymatically modified cholesterol
steroid hormone examples
estrogen, progesterone, testosterone
modified amino acid hormone subclass
n/a
modified amino acid hormones hydrophilic or lipophilic
both- hydrophilic and lipophilic
modified amino acids strucutre/precursor
enzymatically modified amino acids
modified amino acid hormone examples
thyroid hormone
hormone like
prostaglandinsp
prostaglandins
lipid derived signaling molecules; sometimes get into blood, sometimes don’t; act locally
g-protein coupled receptors
7 transmembrane domain receptors; extracellular; second messenger system
receptor tyrosine kinsases
phosphorylation/activation of effector proteins; extracellular
intracellular receptors
nuclear receptors, ligand induced transcription factors (make new proteins)
additive effects
summation of the response of each hormone
synergistic effect
effects of 2 or more hormones are greater than predicited by adding the effect of each hormone
permissive factors
one hormone must be present to have full effect of another hormone
antagonistic effects
2 hormones have opposing effects
ligand
molecule that binds a receptor
receptor
a molecule that responds specificially to neurotransmitters, hormones, antigens, light, pressure or other substances, binding is competitive and saturable
agonist
molecule that activates a receptor
antagonist
molecule that binds to a receptor and does nothing
protein hormone synthesis
translation (RNA), initial processing, prohormone passes thru golgi, packaged, released, into circulation
preprohormone
signal sequence directs amino acid chain to ER; necessary for secreted proteins
prohormone
many peptide/protein hormones are synthesized with extra amino acids are cut out; can be multiple hormones from one gene
major steroid hormone classes
estrogens, androgens, progestins, glucocorticoids, mineralocorticoids
where are steroidogenic cells located
ovary, testes, placenta, fat, brain
steroid hormone precursor
cholesterol
where does majority of cholesterol come from
diet
what is the other way we get cholesterol
de novo synthesis (cells make it)
steroidogenic acute regulatory protein (StAR) function
transports cholesterol from outer to inner mitochondrial membrane
what is the rate limiting step for steroidogenesis
steroidogenic acute regulatory protein
increased amount of LH, FSH, ACTH leads to
increased steroidogenic acute regulatory protein activity
what is P450scc
enzyme that absorbs light at 450nm; cholesterol side chain cleavage
where is P450scc found
inner mitochondrial membrane
what enzyme starts delta-4
3-beta-hydroxysteroid dehydrogenase (3β-HSD)
what does 3β-HSD make
progesterone
what enzyme starts the delta-5 pathway
17α-hydroxylase
what does CYP17A1 produce
17α-hydroxypregnenolone → DHEA
name the key enzymes involved with testosterone production
StAR, P450scc, 3β-HSD, 17α-hydroxylase, 17/20 lyase, 17β-HSD
what does LH upregulate
StAR, P450scc, P450 17a
how is DHT made
testosterone to DHT via 5α-reductase
can DHT become estradiol
no
estradiol cell types
theca cells (1st) and granulosa cells (2nd)
what do theca cells produce
androgens (testosterone, androstendione)
what does LH stimulate
StAR, P450scc, P450 17a
what do granulosa cells produce
estradiol
what does FSH increase
aromatase and 17β-HSD
what does aromatase convert
testosterone to estradiol
what does 17β-HSD convert
androstenedione to testosterone
major steroid families
mineralocorticorids, glucocorticoids, androgens, estrogens
mineralocorticoids key hormone
aldosterone
glucocorticoids key hormone
cortisol
androgens key hormone
DHEA, testosterone, DHT
estrogens key hormones
estradiol, estrone, estriol
steroid hormone release
can diffuse through plasma membrane, cannot be stored in cells
is steroid hormone release regulated
no only steroid hormone synthesis is regulated
low LH and low FSH
low estrodiol and low androgens
high LH and low FSH
high androgens, low or normal estrodiol
steroid hormone mode of action
through the blood bound to carrier proteins
sex hormone binding globulin
albumin
where can steroids bind
membrane receptors and intracellular receptors
when steroid hormones bind to membrane receptors it lead to
rapid effects
what happens when the hormone bind to the intracellular receptor in the nucleus
dimerizes and increases transcription
what happens when the hormone binds the the intracellular receptor in the cytoplasm
dimerizes, translocates to the nucleus and increases transcription
hormone response time when binding intracellularly
slow (hours to days)
precursor for prostaglandins
arachidonic acid
prostoglandins signalling method
GPCRs
anterior pituitary gland
epithelial cells, connected to hypothalamus via portal blood system
posterior pituitary gland
neural cells, axons that project from the hypothalamus
posterior pituitary gland secretes
oxytocin
HPG axis
hypothalamic pituitary gonadal axis
where are kisspeptin and GNRH located
hypothalamus
kisspeptin
two populations, regulate GnRH neuron activity
gonadotropic releasing hormone (GnRH)
stimulates pituitary release of LH and FSH
where are lutenizing hormone and follicle stimulating hormone kept
anterior pituitary gland
luteinizing hormone (LH)
acts on gonads to promote steroidgenesis
follicle stimulating hormone (FSH)
supports gametogenesis and follicular/spermatogenic development
where is estradiol, progesterone, and testosterone kept
gonads
estradiol
key sex steroid regulating feedback to hypothalamus/pituitary
progesterone
supports reproductive cycles and negative feedback
testosterone
drive male secondary sex characteristics and spermatogenesis
spermatogenesis
production of sex steroids
gametogenesis
formation of eggs or sperm
negative feedback
self regulating to maintain hormone concentrations at a given set point