endocrine Flashcards
1
Q
endocrine system
A
one of two major systems for communication
cells of endocrine glands produce chemical messengers within the glands that influence tissues separated from the glands by some distance
chemical messengers are hormones - signaling molecules
2
Q
2 main regulatory systems
A
nervous system: precise, rapid, finely adjusted, short term regulation
endocrine system: slower, more sustained control over long term processes like growth and reproduction
3
Q
2 glandular systems in the body
A
exocrine glands: glands that empty their secretion into body cavities or onto body surfaces; do so through tubular ducts
endocrine glands: ductless system composed of glands that release secretion internally into the bloodstream
4
Q
glands of the endocrine system
A
- pituitary gland
- hypothalamus
- thyroid gland
- parathyroid glands
- adrenal glands
- pancreas
- gonads
5
Q
characteristics of endocrine glands
A
- paired or unpaired
- organs or scattered cells
- one or more cell-types
- cells may secrete one or more hormones
- cells in clumps, cords, or scattered
- cells may have smooth ER or rough ER
- cells may/may not have secretory vesicles
- cells may/may not have lipid droplets
6
Q
endocrine glands are highly vascularized bc
A
secrete chemical messengers into the circulatory system
- all hormones are made from dietary precursors, so endocrine glands need a large blood supply to provide the precursors
- rely on the bloodstream to transport hormones to target sites
7
Q
paracrine signaling
A
hormones, or paracrine substance, is released from the cell but it will act on neighboring cells (close proximity to site of release) rather than on distant target sites
8
Q
autocrine signaling
A
hormone or autocrine substance is released into extracellular space and acts on the cell from which it was released
9
Q
endocrine signaling
A
a hormone is released into the bloodstream and acts on distant target sites
10
Q
nervous signaling
A
a messenger molecule (neurotransmitter) is released into a synapse close to the target site, which is either another neuron or an effector cell
11
Q
neuroendocrine signaling
A
these tissues, instead of releasing secretion into a synpase, release secretions into a blood supply
neural tissue releasing its chemical messenger into the blood stream and not into a synapse
neuroendocrine cells receive neuronal input, which is a neurotransmitter released by nerve cells; as a consequence of this input, neuroendocrine cells release messenger molecules into the blood
12
Q
hormone characteristics
A
- chemical messengers that regulate homeostasis: set in motion biological reactions but rarely produce de novo actions; regulate the rate of pre-existing actions
- high potency: a very small amount of hormone will produce a biological effect; biologically active at low conc
- actions are mediated through specific receptors
- act with a latency, or delay, of response
- have limited storage
- most are secreted irregularly in phases: not continuous
- mostly carried in the blood by binding proteins
- none are used as an energy source
- none are incorporated into another molecule
13
Q
2 main groups of hormones
A
steroid hormones: derived from cholesterol
protein hormones: amines - derived from a single amino acid (tyrosine); peptides - short chains of amino acids; proteins - longer polypeptides
14
Q
steroid hormones
A
all derived from cholesterol
- cholesterol enters the cell bound to LDL (low-density lipoprotein - major carrier of plasma cholesterol to cells)
- cholesterol is derived from the diet and can be stored in the cell as a liquid droplet until needed
- cholesterol can also be synthesized within the cell from acetate
- once cholesterol is inside the cell, it can be moved to the mitochondria where it undergoes the first step in steroid biogenesis (pregnenolone)
- steroid hormones are lipid soluble so they can easily diffuse through the plasma membrane throughout the cell
- steroid hormones are released by diffusion
15
Q
protein hormones
A
all made from translation of messenger RNA
- a gene containing the info for the protein hormones is transcribed into mRNA in the nucleus
- mRNA -> pre-hormone -> pro-hormone -> hormone
- hormones are packaged into secretory vesicles after passage through the Golgi apparatus and move to the plasma membrane; content of the vesicles are released
16
Q
secretory vesicles
A
a vesicle that mediates the vesicular transport of cargo, such as hormones or neurotransmitters, from an organelle to specific sites at the cell membrane, where it docks and fuses to release its contents
17
Q
roles of secretory vesicles
A
- protect the hormone from proteolytic degradation
- provide a reservoir in sites of synthesis
- provide a transport mechanism along the microtubules and microfilaments of the cell to the site of release, which is the cell membrane
- provide a release mechanism (exocytosis)
- provide for quantal release (composed of discrete units)
18
Q
2 types of hormones in plasma
A
bound and free
19
Q
free vs bound hormone
A
only the free hormone is biologically active - can bind to its target receptor
when the hormone is bound to a binding protein, it is inactive - cannot bind to its target receptor
20
Q
roles of binding proteins
A
- inc the solubility and conc of lipid-soluble hormones, which includes all lipid soluble steroid hormones and thyroid hormones (thyroid hormones are derived from amino acids but they are lipid soluble)
- inc the size of the hormone, protecting the hormones from clearance by the kidney, degrading by the liver and the kidney, and from degradation by plasma enzymes
- inactivates free hormones, providing a buffer against large and sudden changes in the hormone conc
- the level of protein binding is dynamically regulated with the rate of secretion, rate of degradation and the rate of hormone binding to receptors in target tissues
21
Q
hormone secretion
A
dynamically regulated to maintain a steady-state around a set-point or range, that may vary during the day or with age of physiological state
- hormones are released episodically
- an inc in the number of episodes of release will inc the level of hormone in the blood
- an inc mean level of hormone in the blood can be achieved by an inc in the frequency of release or the amplitude of release
- diurnal secretion: having a 24 hour period or cycle, daily
22
Q
negative feedback
A
most common type of inhibition
inhibits hormone secretion when circulating levels are high and inc hormone secretion when circulating levels are low
23
Q
positive feedback
A
rare, but allows discreet physiological events to be rapidly attained after which a catastrophic collapse in the system occurs where there is participation of negative feedback inhibitory signals that will terminate secretion rates
24
Q
negative feedback pathway
A
endocrine gland releases the hormone -> hormone travels in the blood to act at its target site -> causes release of a product into the bloodstream -> product will cause suppression of the gland -> dec in secretion of the hormone from the gland
25
positive feedback pathway
endocrine gland releases hormone -> acts on the target cell or tissue -> produces a product (often another hormone) -> product will then feedback on the endocrine gland from which the first hormone was released to stimulate it
26
first requirement for hormone action
binding of a hormone to a specific receptor
27
hormone action
feedback is a measure of hormone action and reflects the action of a hormone at a target site
need a receptor to respond to a signaling molecule
28
hormone receptors
lock (receptor) and key (hormone) interaction
29
cAMP second messenger system
protein-hormones cannot cross the cell membrane and must bind to membrane-bound receptors
- these receptors act through G-proteins and second messenger systems to produce a response in the cells
30
signal amplification
signal transduction mechanisms allow for amplification of these response following binding of a hormone to its receptor
31
nuclear receptors
includes steroid and thyroid hormones
receptors are located in the nucleus of the cell
bind to receptors in the nucleus and produce effects through altering protein synthesis
32
cytoplasmic receptors
receptor is involved in intracellular transport
provide a reservoir of the hormone within the target site
some of the cytoplasmic receptors are found in organelles such as the mitochondria
thyroid hormones have nuclear receptors and cytoplasmic receptors
33
up-regulation
more receptors
an inc in the number of target-cell receptors for a given messenger in response to chronic low extracellular conc of that messenger
will occur at low hormone conc to inc the biological response
results from inc receptor synthesis or dec receptor degradation
34
sensitization
more affinity
affinity reflects stability of binding; a high affinity means that the hormone and receptor bind to each other tightly
this can occur at low hormones conc to inc the activity of the hormone
results from conformation changes in the lock structure
35
down regulation
cells down-regulate receptors in response to elevated (high) hormone conc in the blood
36
down-regulation by coated pits
membrane bound receptors are found in the plasma membrane and can move laterally along the plasma membrane, or within the plane of the bilayer
hormone receptor complexes congregate in certain areas of the cell over regions called coated pits
- membrane invaginates where the hormone receptor complexes are found or localized together
- hormone receptor complexes are vesiculized, or contained in vesicles
- lysozymes fuse with the vesicle and the lysosomal enzymes cleave the hormone from its receptor
- down regulation by coated pits allow protein hormones to enter the cell, but this type of mechanism will allow long-term responses to occur
37
endocrine dysfunction
primary defects in the rates of hormone synthesis - problem with the endocrine gland
defect on the regulation of hormone - problem in hormone action bc hormone action requires feedback
defect in hormone action - problem with the target tissue/tissue resistance
38
hypophysis =
pituitary gladn
39
pituitary gland
- found in ventral part of the brain (base)
- lies just below the hypothalamus
- 2 separate endocrine tissues: anterior pituitary, posterior pituitary
40
neurohypophysis
posterior pituitary of pituitary gland
- down growth from the brain or hypothalamus
- neural tissue
41
adenohypophysis
anterior pituitary
derived from non-neural tissue
reflects tissue which results from the invagination of the roof of the mouth, called the hypophyseal pouch or Rathke's pouch
42
intermediate lobe
btw anterior and posterior pituitary
lost before birth in humans
scattered endocrine cells remain
43
hypothalamic nuclei
paraventricular nuclei and supraoptic nuclei
- nuclei produce the hormones that are released by the posterior pituitary
- the hormones are synthesized in the cell bodies of the nuclei, whose long axons pass down the infundibulum and end in the posterior pituitary gland
- the hormones are stored in the posterior pituitary until stimuli cause action potentials to propagate to the axon terminals and trigger release of the hormones by exocytosis
- the hormones then enter capillaries into the systemic circulation
44
infundibulum
pituitary stick
contains the axons of the neurons in the hypothalamus and blood vessels
45
2 neural secretions released from the posterior pituitary
antidiuretic hormone (ADH) or vasopressin: most ADH is produced in the supraoptic nuclei (5/6)
oxytocin: most oxytocin is produced in the paraventricular nuclei (5/6)
the remaining 1/6th of each hormone is produced in the opposite nuclei
46
oxytocin and ADH involve the synthesis of a
preprohormone
ADH: first product produced is call pre-pressophysin; converted to ADH; ADH connected to a binding protein called neurophysin (intraneural binding protein) -> neurophysins transport the small hormone down the axon to the vesicles, or the neurosecretory granules, in the nerve that releases the hormone -> after release neurophysin dissociates from the hormone -> neurophysin has no biological effect
47
synthesis of protein hormones in nerves
hormone is produced in the cell body of the neuron -> packaged in the golgi apparatus -> transported along the axon to the nerve terminal -> stored in the nerve terminals until an appropriate stimulus causes its release into the extracellular space -> hormone then moves into the blood
48
vasoconstriction actions of ADH
causes contraction of the smooth muscle around blood vessels
causes an inc in blood pressure
only occurs at high conc of the hormone such as during a blood loss (hemorrhage)
49
anti-diuretic actions of ADH
control fluid balance in the body by reducing urination
inc the permeability of the renal collecting duct
- ADH inc the number of water channels in the collecting duct
- in the absence of ADH, the collecting ducts are virtually impermeable to water, and it flows out as urine
causes vasoconstriction of the glomerular tubules, reducing the glomerular filtration rate
causes contraction that reduces the size of the glomerulosa cells therefore reducing the surface area for filtration
50
mechanism of ADH action
- ADH in the circulation will travel to the kidneys
- ADH binds to its receptors on the collecting cells
- binding of ADH to its receptor induces synthesis of a second messenger (cAMP)
- cAMP causes the up-regulation of the aquaporin 2 protein via gene transcription - allows water to be reabsorbed from filtered urine
51
factors affecting secretion of ADH
plasma volume
plasma osmolarity
52
osmol sensitive
react to changes in blood osmolarity
53
baroreceptors
blood volume affects blood pressure
detect changes in blood pressure
54
2 types of nuclei in the hypothalamus are osmoreceptors
supraoptic nucleus (SON)
paraventricular nucleus (PVN)
55
main stimuli for ADH release
dec in blood volume or inc in blood osmolarity
56
relationship between plasma osmolarity and ADH secretion
linear
with an inc in plasma osmolarity, there is an inc in plasma ADH levels
57
relationship between mean arterial pressure and plasma ADH levels
linear
decline in mean arteriole pressure results in ADH release
58
ADH secretion increased by
stress/emotion
heat
nicotine
caffeine
59
ADH secretion decreased by
cold
alcohol
60
ADH action
synthesis: SON
secretion: posterior pituitary
actions: inc water retention, inc vasoconstriction
stimuli: inc osmolarity, dec blood volume
61
diabetes insipidus
ADH deficiency
- hypothalamic/central diabetes insipidus -> problem of ADH production
- nephrogenic diabetes insipidus -> problem of ADH action
62
syndrome of inappropriate ADH (SIADH)
excess ADH
problem of ADH production, feedback failure
- dec aldosterone secretion from the adrenal cortex -> dec sodium reabsorption and promotes sodium excretion
- inc ADH levels and dec aldosterone levels results n hyponatremia, or low blood sodium levels
63
polyuria
produce large amounts of dilute urine
64
polydipsia
excessive thirst and fluid intake
65
oxytocin
released from posterior pituitary
produced in the paraventricular nuclei (PVN) in the hypothalamus
66
oxytocin actions
uterine myometrium: parturition, oxytocin clamps ruptured blood vessels to prevent hemorrhage, restoration of the pre-pregnancy uterine size, stimulation of the movement of sperm in the female reproductive tract, movement of the cervix
mammary myometrium: stimulates milk letdown
67
oxytocin action summary
synthesis: PVN
secretion: posterior pituitary
actions: inc lactation, inc uterine motility
stimuli: genital, uterine, breast stimulation
68
deficiency of oxytocin
impaired delivery
impaired lactation
69
excess oxytocin
no problems associated with high levels of oxytocin
70
anterior pituitary
produces hormones essential for growth and reproduction
controlled by the hypothalamus through the blood supply
71
blood supply
median eminence-capillary bed which receives axons from nuclei in the hypothalamus; gives rise to the hypothalamo-hypophyseal portal vessels (venous of portal blood vessels which run into the anterior pituitary)
short portal vessel (blood vessel which comes from the capillary bed in the posterior pituitary
secretions from the hypothalamus are released into the capillary beds
72
nuclei of hypothalamus
parvocellular neurons
- neurons with small cell bodies with short axons
- nuclei who axons end in the median eminence
- produce neural secretions that are released into the blood vessels which carry these secretions down to the anterior pituitary to act on the pituitary cell types
magnocellular neurons
- neuroendocrine cells located in the hypothalamus
- among the largest cells in the brain
- synthesize the hormones oxytocin and ADH/vasopressin
- paraventricular and supraoptic nuclei
73
vascular link btw the hypothalamus and pituitary
- neural secretions from the hypothalamus are released into capillaries in median eminence
- blood flows into anterior pituitary through the hypothalamic-hypophyseal portal vessels
- hypophysiotropic hormones control hormone secretion by acting on cells in the anterior pituitary
74
anterior pituitary gland hormones
secretion largely regulated by hormones produced by the hypothalamus and collectively called hypophysiotropic hormones
- gonadotropins: LH and FSH - stimulate gonad activity
- GH: stimulates growth
- TSH: stimulates thyroid gland
- PRL: acts on the mammary glands to affect milk formation; acts on the gonads
- ACTH: acts on the adrenal gland
75
hypothalamic-releasing hormones
from hypothalamus: neural secretions
stimulate of inhibit the release of the anterior pituitary hormones
- GnRH: stimulates release of LH and FSH
- GHRH: stimulates release of GH
- TRH: stimulates release of TSH and PRL
- PRFs: stimulates release of PRL
- CRH: stimulates release of ACTH
- SRIF: inhibits the release of GH and TSH
- PIFs: inhibits release of TSH and PRL
76
secretions of the anterior pituitary
- TSH: stimulates thyroid gland -> secrete T3 and T4
- ACTH: stimulates adrenal cortex -> secrete cortisol
- gonadotropins LH and FSH: stimulate gonads -> secrete sex hormones and regulate growth and development of gamete production
- GH: acts on most tissues of the body. number of effects related to intermediary metabolism, acts through the liver through hormones called somatomedins
77
autoregulatory loop
most hormones are released into the systemic circulation, but can move backwards along the blood vessels that emanate from the median eminence of the neural tube
- retrograde flow along the blood vessels
78
effects of GH
- muscle, lover and adipose tissue
- induces protein synthesis in all tissue containing protein -> anabolic in muscle
- adipose tissue inc lipolysis, or the breakdown of fats and other lipids
- induces production of somatomedins (insulin-like growth factors)
79
factors regulating growth hormone secretion
from the hypothalamus: GHIH, somatostatin, GHRH
- GH inc by: deep sleep, exercise, stress or reduced blood glucose levels, inc blood amino acids, dec blood fatty acids
- pronounced diurnal rhythm
- negative feedback
80
GH release factors
number and amplitude of GH release inc by fasting, meals in amino acids
dec from meals high in glucose or fatty acids
81
summary of GH
synthesis: somatotrophs
secretion: episodic, more during stress/sleep, less during aging, GHRH/SRIF balance
action: skeletal/soft tissue growth, hyperglycemia hyperlipidemia, IGF-1 induction (somatomedins; negative feedback)
82
deficiency of GH
in juveniles: dwarfism
- isolated GH deficiency (type 1): a defect in GH production
- laron-type dwarfism: a defect in GH action bc there are problems with the GH receptors (IGF-1 levels are deficient)
normal body proportions for age, no intellectual disability, usually mature sexually
83
thyroid dwarfs
have the body proportions of an individual much younger than themselves
84
GH deficiency in adults
somatopause
- inc in fat production and a dec in lean body mass
- metabolic disturbances
- impaired immune function
- thymic atrophy
- exogenous GH admin is not recommended
85
excess GH
over-secretion in childhood causes pituitary gigantism
acromegaly - in adults
- bones in face, hands, feet, cartilage enlarge and widen
- protruding lower jaw (prognathism)
- internal organs inc in size
- inc release of glucose leads to development of diabetes
- due to a GH-secreting tumor of the pituitary
- hirsutism
- gynecomastia or enlarged breast tissue in males
86
prolactin
released from anterior pituirtary
- gonadal modulator: pro-gonadal when gonadal activity is low; anti-gonadal when gonadal activity is high
- mammary gland development
- involved in lactation of milk production
87
prolactin releasing factors (PRFs)
stimulates prolactin secretion
TRH and oxytocin
gonadal steroid hormones: estrogen and testosterone inc prolactin secretion; progesterone will inhibit prolactin secretion
mammary stimulation: suckling stimulates prolactin release
88
hyperprolactinemia
excess prolactin
- accompanied by gonadal dysfunction, amenorrhea, reduced libido
- treated with a dopamine agonist
89
hypoprolactinemia
deficiency in prolactin
gonadal dysfunction, impairment of lactation
90
pituitary diabetes
excess of all anterior pituitary hormones
- hyperglycemia
91
hypopituitarism
deficiency in pituitary hormone production
92
panhypopituitarism
affects all of the pituitary hormones
93
hypothalamic-pituitary-thyroid axis
hypothalamus releases thyrotropin-releasing hormone (TRH) into the hypothalamo-hypophyseal portal vessels -> TRH acts on the anterior pituitary to release thyroid-stimulating hormone -> TSH acts on the thyroid gland to produce T3 and T4 which act on target cells
- receptors for thyroid hormone are present in the nuclei of most cells in the body
- stress inhibits this axis
- in infants cold will promote the axis
94
thyroid hormones
inc metabolic rate and heat production, enhance growth and CNS development and enhance sympathetic activity
95
TSH
peptide hormone produced by anterior pituitary cells called thyrotrophs
- stimulates growth of the thyroid gland
- stimulates the biosynthesis of thyroid hormones
96
glycoprotein hormones
contain sugar residues - glycosylated
2 subunits: alpha and beta
- biological activity resides in the beta
- sugars are essential to biological activity, promote receptor recognition and prevent degradation of the hormone
97
thyroid gland
vascular structure (has good blood supply)
capsule of connective tissue covers the thyroid gland, which is made up of many secretory parts called follicles (basic unit of the thyroid gland)
- the follicles have cavities lined with a single layer of cuboidal epithelial cells called follicular cells: cavities are filled with a clear viscous protein-rich substance called colloid; when the gland is active, the follicular cells enlarge and the colloid shrinks in size; the colloid consists primarily of glycoprotein called thyroglobulin (synthesized in the follicular cells and secreted into the colloid)
- colloid is the site of thyroid biosynthesis
98
thyroglobulin
precursor for thyroid hormone biosynthesis
- glycoprotein
- synthesized in the follicular cells in the rough endoplasmic reticulum
- secreted into the colloid
- contains numerous tyrosine residues which provide a template for thyroid hormone synthesis
- NOT a thyroid hormone binding protein
99
2 thyroid hormones
T3 (triiodothyronine)
T4 (tetraiodothyronine)
- T4 is a precursor hormone: degraded by deiodinase enzymes to T3; in this process an iodine is lost from thyroxine; this inc the biological activity of the thyroid hormone; T3 is at last three to five times more biologically active than T4; large percentage of T4 is converted to T3 in peripheral tissues; only hormones which contain iodine
100
synthesis of thyroid hormones
iodine is transported with sodium ions across the basolateral membrane of the follicle cell, from the interstitial fluid into the follicular cell
the negatively charged iodine ions diffuse to the apical membrane of the follicular cells and are transported into the colloid by an anion transporter
101
TG synthesis
synthesized in the follicular cells and released into the colloid by exocytosis
102
thyroid hormone synthesis summary
assembly of raw material: tyrosine, iodine
iodination of tyrosine (thyroid peroxidase): Tyr + 1 iodine = MIT; MIT + 1 iodine = DIT
coupling/condensation of iodotyrosine: MIT+DIT = T3; DIT+DIT = T4
when thyroid hormones are ready to be released into circulation they must be carried by binding proteins in the blood, as they are lipid soluble
103
thyroid hormone receptors are
ubiquitous (found everywhere)
104
effects of thyroid hormone
effect on basal metabolic rate and heat production:
- inc basal metabolic rate
- inc O2 and glucose uptake, mitochondrial enzymes
- calorigenic effect
promotes neural activity:
- inc irritability, mentation, beta receptors
- dec reflex times
cardiovascular action
intermediary metabolism:
- carb absorption
- dec plasma cholesterol
growth and development:
- psychogenic/physical
- growth hormones synergy
105
3 types of receptors
membrane bound receptor: receptors are linked to channels within the membrane
- binding of the hormone to the receptor will open the channels and allow glucose to enter
cytoplasmic receptors: thyroid hormones that have entered by diffusion or through a carrier can bind; act as a reservoir of thyroid hormone in the target tissue; cytoplasmic receptors may also be present on internal organelles
nuclear receptors: affect gene transcription and protein synthesis
106
thyroid hormones unique features
- synthesized and stored extracellularly in colloid
- only hormones that contain iodine
- lipid soluble or hydrophobic even though they are derived from amino acids
- secreted by diffusion and carried in plasma by binding proteins
- mechanism of action: membrane, cytoplasmic, or nuclear receptors
107
thyroid hormone excess
hyperthyroidism
inc basal metabolic rate
causes: primary problem with the thyroid gland; secondary problem caused by the pituitary gland; tertiary problem caused by hypothalamus
108
grave's disease
autoimmune disease in which antibodies develop against TSH receptors
- large swelling or goiter in the neck
- overstimulation of the growth and activity of the thyroid gland
- exophthalmos, or bulging of the eyes
109
hyperthyroid characterisitics
- exopthalamus
- goiter
- inc basal metabolic rate
- tachycardia or heart palpitations
- inc signs of sympathetic nervous system activation
110
