Studied by 25 people
what is the relationship between animal size and animal cell number? what does this relationship illustrate?
as animal size increase, animal cell number increases
the endocrine system is necessary for effective communication across millions/trillions of cells
what are 4 kinds of cell signaling?
direct cell signaling via gap junctions
autocrine/paracrine signaling
endocrine signaling
neural signaling
describe autocrine/paracrine cell-to-cell communication
secretory cell - various
target cell - various
signal type - chemical
max signaling distance - short
transport between cells - interstitial fluid (fluid between cells)
speed - rapid
duration of response - short
describe nervous cell-to-cell communication
secretory cell - neural
target cell - neuron, muscle, adipose, endocrine, exocrine
signal type - chemical and electrical
max signaling distance - can be long intracellularly, short across synapse
transport between cells - synapse
speed - rapid
duration of response - short
describe endocrine cell-to-cell communication
secretory cell - endocrine
target cell - various
signal type - chemical
max signaling distance - long
transport between cells - circulatory fluids
speed - slower
duration of response - longer
describe inter-individual cell-to-cell communication
secretory cell - exocrine and various epithelial cells
target cell - sensory and neural
signal type - chemical
max signaling distance - very long
transport between cells - external environment
speed - various
duration of response - various
what is the difference between autocrine/paracrine signaling and endocrine signaling?
autocrine/paracrine signaling is when a cell sends a messenger out and it affects a nearby target cell (or the cell itself, for autocrine)
endocrine signaling is when a cell sends a messenger (hormone) out and it affects a multitude of target cells, as hormones can travel through blood and lymph, and has a variety of effects
what is the classical definition of hormones?
a chemical substance produced by specialized organs called endocrine glands and transported through the bloodstream to other tissues, where they act to elicit a specific physiological response
what is the difference between exocrine and endocrine glands?
exocrine glands secrete substances to the external environment, have ducts, and are poorly vascularized
ex. sebaceous glands, lacrimal glands, etc.
endocrine glands secrete substances to the internal environment, don’t have ducts, and are highly vascularized
ex. pineal, pituitary, etc.
what is an important point about the gut mentioned in lecture?
the gut is a part of the ‘external environment’
what can be issues regarding hormones and their functions?
too much of a hormone
not enough of a hormone
malfunctioning hormone receptors (not sensitive enough or too sensitive)
describe cushing’s syndrome symptoms
occurs from adrenal or pituitary abnormalities, ACTH-dependent or ACTH-independent
high BP
round “moon” face
abdominal obesity and thin extremities
thin skin and stretch marks
fat pad between shoulder blades
hirsutism (hair in places it’s not supposed to be)
describe addison’s disease symptoms
rare autoimmune disease associated with high plasma ACTH concentration, loss of negative feedback
fatigue and muscle weakness
lower back pain
low BP
hyperpigmentation around joints (could be because of similarities between cortisol and melanin)
anxiety and depression
describe graves disease symptoms
ophthalmopathy
insomnia
hand tremors
hyperactivity
hyperhidrosis
what is the broad definition of hormones?
chemical substances released by one cell which act on another cell
what is the reason for having two definitions for hormones?
the classical definition proved to be too specific, and didn’t include chemical messengers that aren’t produced by specialized cells, like IGF-1, or only work locally
how are hormones divided into groups?
based on hydrophobicity
describe hydrophilic messengers
storage - intracellular vesicles
secretion - exocytosis
transport - dissolved into extracellular fluids
receptor - transmembrane
effects - rapid
describe hydrophobic messengers
storage - synthesized on demand
secretion - diffusion across membrane
transport - dissolved in extracellular fluids for short distances, bound to carrier proteins for long distances
receptor - intracellular or transmembrane
effects - slower or rapid
what are the three types of hormones/chemical messengers covered in this course?
peptides, steroids, and amines
describe peptide/protein hormones
hydrophilic, soluble in aqueous solutions and travels to target cell dissolved in extracellular fluid
bind to transmembrane receptors and start signal transduction
rapid effects on target cell
relatively large
name typically ends in -in
describe peptide hormone production and release
preprohormones are synthesized in the rough ER
the pre- portion (signal sequence) is cleaved off in the rough ER
the prohormone goes to the Golgi apparatus, which may or may not modify it, and then is packaged into a vesicle to be released
the pro- portion is cleaved from the hormone, which activates the hormone
what is actually released into extracellular fluid during peptide hormone release?
active hormone and a peptide fragment
describe amine hormones
possess an amine group (-NH2)
ex. ACh, dopamine, norepinephrine, serotonin, histamine, thyroid hormones
name typically ends in -ine
sometimes called biogenic amines
some can act as neurotransmitters, hormones, or both
hydrophilic (except for thyroid hormones)
have diverse effects
describe steroid hormones
derived from cholesterol and synthesized by smooth ER or mitochondria
three classes of steroid hormones:
mineralocorticoids like aldosterone (electrolyte balance)
glucocorticoids like cortisol (stress hormones)
reproductive hormones like testosterone (sex-specific characteristics)
hydrophobic, made on demand and can diffuse through plasma membrane, can’t be stored
transported to target cell via carrier proteins (albumin)
bind to intracellular or transmembrane receptors (usually intracellular)
name typically ends in -one
how are steroids transported through the blood and allowed to enter the target cell?
the messenger concentration moves from high to low towards the target cell, with most messengers bound to carrier proteins
free messengers enter the target cell, decreasing the concentration of free messengers and prompting bound messengers to dissociate, allowing them to enter the target cell as well
describe the genomic effect for steroids
the steroid will diffuse through the cellular membrane and bind to an intracellular receptor, forming a steroid-receptor complex
the complex will bind to DNA and affect gene transcription
slow effects
what steroid is an exemption from the genomic effect pathway?
cortisol has rapid, non-genomic effects
what are receptors?
they exist on target cells, either in the membrane or inside the cell
they change shape/conformation which bound by the ligand
what are ligands?
chemical messengers that bind to receptors
hormone can be aka as natural ligand
what are agonists?
ligands that bind to and activate receptors, not necessarily the natural ligand
what are antagonists?
ligands that bind to and don’t activate receptors, they prevent ligand binding
what will increase a cellular response, in terms of ligands and receptors?
more free ligands or receptors will increase a cellular response
what is the law of mass action?
receptors can become saturated at high levels and the associated response is maximal
what is the effect of receptor concentration on maximal response?
larger receptor concentration allows for a larger maximal response
what is the effect of receptor affinity on rate of receptor response?
high-affinity receptors reach receptor saturation at a faster rate
what is the connection between Kd values and receptor affinity?
a lower Kd value corresponds to a high receptor affinity
the response of a cell to a particular chemical messenger is determined by the:
The ligand-binding domain and the functional domain
ligand-binding domain
transmembrane domain
functional domains
chemical messenger itself
ligand-binding domain
what are some ways to inactivate the ligand-receptor complex?
remove the ligand
degrade the ligand
remove the L-R complex entirely
inactivate the receptor via phosphorylation
inactivate the signal transduction pathway
describe ligand-receptor interactions
isoreceptor hypothesis: a ligand can bind to more than one type of receptor with different target cells and different responses
a single cell may have receptors for many different ligands
receptors can accept many different but related ligands
describe intracellular receptors
used for steroids
the ligand will diffuse through the cell and bind to the receptor in the cytoplasm/nucleus
the L-R complex binds to specific DNA sequences and regulates the transcription of target genes (increases/decreases production of specific mRNA)
describe receptor-enzyme proteins
aka enzyme-associated receptors
this receptor is an enzyme/catalyst on its own, composed of a ligand-binding site for hormones and a catalytic site inside the cell
three types: guanylate cyclase, tyrosine kinase, serine/threonine kinase
has a large effect due to amplification
describe how guanylate cyclase receptors work
ligand binds to the receptor, changing its conformation
the activated receptor converts GTP to cGMP, which binds to PKG
activated PKG phosphorylates proteins on serine or threonine residue, creating a cascade
describe how tyrosine kinase receptors work
they always require two receptors, will dimerize when a ligand binds
these two connected receptors will autophosphorylate
phosphorylated receptors interact with protein kinases, which then activate Ras protein (on a timer)
activated Ras has GTP instead of GDP, and eventually will autodephosphorylate
Ras switches between active and inactive forms depending on the system needs
describe how serine/threonine kinase receptors work
when a ligand binds to the Type I receptor, the receptor dimerizes (splits into two parts) with Type I and Type II
Type II receptor phosphorylates the Type I receptor to activate it
activated Type I phosphorylates SMAD protein, which when activated, enters the nucleus and regulates gene expression
describe g-protein coupled receptors
they have a binding site for ligands and a g subunit on the inside of the cell
when the protein is activated, the g-protein converts GDP to GTP, activating adenylate cyclase
activated adenylate cyclase converts ATP to cAMP
cAMP binds to PKA, which then causes it to activate and cause effects within the cell
G-protein coupled receptors are a diverse family with which common feature?
They are activated when the alpha-subunit binds to the Beta and Gamma-subunits
They are activated when GTP is released from the G protein
They are activated when a kinase molecule phosphorylates them
They are activated when GTP binds to the G protein
They are activated when GTP binds to the G protein
which of the following is NOT a second messenger utilized by G proteins?
Ca2+
cGMP
phosphatidyl inositol
Na+
Na+
how does the hypothalamus communicate with the anterior pituitary gland?
the anterior pituitary receives blood with neurohormones from the hypothalamus via the hypothalamic-pituitary portal system, and then the anterior pituitary releases tropic hormones to the target cells
what are the hormones associated with the anterior pituitary?
growth hormone, prolactin, thyroid-stimulating hormone, adrenocorticotropic hormone, follicle stimulating hormone, and luteinizing hormone
how can you know which hormones are released from the hypothalamus?
they’re either releasing hormones or inhibiting hormones
what are the hypothalamic hormones for growth hormone?
growth hormone releasing hormone (GHRH) and growth hormone inhibiting hormone (GHIH) or somatostatin
what is the target for growth hormone and what are the effects?
many tissues are targeted
GH promotes growth
what are the hypothalamic hormones for prolactin?
prolactin releasing hormone (PRH) and prolactin inhibiting hormone (PIH) or dopamine, TRH can also stimulate prolactin secretion
what is the target for prolactin and what are the effects?
breast tissue
promotes milk production
what is the hypothalamic hormone for thyroid-stimulating hormone?
thyroid-releasing hormone
what is the target for thyroid-stimulating hormone and what are the effects?
thyroid
stimulates release of T3 and T4 (thyroid hormones)
what are the hypothalamic hormones for adrenocorticotropic hormone?
corticotropin releasing hormone (CRH) and somatostatin/GHIH
what is the target for adrenocorticotropic hormone and what are the effects?
adrenal cortex
stimulates cortisol release
what is the hypothalamic hormone for follicle stimulating hormone and luteinizing hormone?
gonadotropin releasing hormone (GnRH)
what is the target for follicle stimulating hormone and luteinizing hormone and what are the effects?
gonads
FSH stimulates gamete production (sperm/egg) and LH stimulates androgen, estrogen, and progestin production
what conditions are associated with oversecretion of GH?
gigantism (if increased GH in early life) and acromegaly (increased GH later in life)
what is a condition associated with lack of GH?
dwarfism
what is the somatomedin hypothesis?
GH targets tissues (especially liver) which then release insulin-like growth factors (IGFs) that cause somatic growth
somatic tissues targeted by GH will also make their own IGFs, causing themselves to grow (paracrine/autocrine signaling)
describe prolactin effects
in mammals: it stimulates mammary glands to produce milk, also plays an important role in promoting maternal behavior through effects on the brain
it’s made in all vertebrates because it has many possible actions:
osmoregulation
reproduction, can inhibit GH secretion
development, considered a tadpole growth hormone
metabolism, affecting lipids and glycogen
hair growth in skin, skin pigmentation, etc.
behavioral effects
describe the effects of thyroxine (thyroid hormone)
thyroid affects metabolism, involved in digestion, heart and muscle function, brain development, and maintenance of bones
what is cretinism?
a condition caused by insufficient thyroid hormone (iodine deficiency) during fetal/neonatal development, characterized by severe mental retardation and growth defects
describe the hypothalamus-pituitary-thyroid axis as it relates to an example of temperature regulation
cold stimulus from sensory neuron signals hypothalamus to secrete thyrotropin-releasing hormone (TRH)
TRH causes the anterior pituitary to secrete thyroid-stimulating hormone (TSH)
the thyroid secretes T3 and T4, targeting body tissues to increase metabolism
what hormones is the posterior pituitary related to?
vasopressin and oxytocin
how is posterior pituitary communication different from that of the anterior pituitary?
it’s directly connected to the hypothalamus
neurosecretory cells from the hypothalamus release neurohormones into the posterior pituitary blood supply
posterior pituitary blood supply carries hormones to their target cells
how does vasopressin work?
it controls blood pressure, similar in structure to oxytocin
vasopressin affects G-protein receptors in the kidneys
ATP converts to cAMP via adenylate cyclase, and cAMP activates protein kinase A
PKA causes phosphorylation of preformed vesicles, fusing it with the cell membrane and inserting aquaporins
how is the cytoskeleton involved in vasopressin intracellular actions?
the cytoskeleton acts as internal structure that allows for movement of preformed vesicles to the cell membrane (similar to filaments within the axon allowing retrograde and anterograde transport)
what is the function of aquaporins on the cell membrane of kidney cells activated by vasopressin?
aquaporins allow for reabsorption of water from urine made in the kidneys, increasing blood pressure
which anterior pituitary hormone is considered a second order feedback hormone?
prolactin
what is the pancreas?
an endocrine and exocrine organ located near the small intestine
what do exocrine glands in the pancreas do?
they produce pancreatic enzymes and sodium bicarbonate, both excreted by the pancreatic duct
what do endocrine glands in the pancreas do?
they produce insulin and glucagon, both for glucose regulation
what is insulin?
a hormone that lowers blood glucose levels under hyperglycemia
it promotes glycogenesis and lipogenesis
what is glucagon?
a hormone that raises blood glucose levels under hypoglycemia
it promotes glycogenolysis, lipolysis, and gluconeogenesis
which cells in the pancreas are endocrine?
islet of langerhans cells, alpha cells make glucagon and beta cells make insulin
which cells in the pancreas are exocrine?
acinar cells
what is produced from delta cells in the pancreas?
somatostatin, an inhibitory hormone
what are some other hormones produced in the pancreas?
gastrin, vasoactive intestinal peptide (VIP)
what is the range of healthy blood sugar?
70 mg/dL to 100 mg/dL
how do insulin and glucagon work together?
their actions are antagonistic, both regulate homeostatic blood glucose levels
what is additivity?
when two hormones work in the same way on the same target
what is synergism?
when two or more hormones work together to increase target cell response much more than expected by additivity
what are three pathways that can regulate insulin secretion?
increase in blood glucose prompts the pancreas to secrete insulin
glucose receptors in the digestive tract will release CCK, which targets the pancreas to secrete insulin
stretch receptors in the digestive tract send information to an integrating center, which targets the pancreas to secrete insulin (feed forward)
describe diabetes mellitus type 1
aka insulin-dependent diabetes, child-onset diabetes, etc.
loss of beta cells of the pancreas, little or no insulin produced
causes: autoimmunity, trauma or substances that damage the pancreas (radiation, surgical removal, etc.), some are idiopathic (unknown cause)
what are symptoms of type 1 diabetes?
whole body is effected: chronic vascular diseases, affects heart, lungs, eyes, skin, etc.
diabetic coma (hyperglycemic or hypoglycemic)
describe a hyperglycemic diabetic coma
heavy breathing, low pH (about 7.1)
results from not taking insulin
describe a hypoglycemic diabetic coma
normal breathing, hypothermia present
results from taking too much insulin
describe treatments for type 1 diabetes
strict control of diet/metabolism
therapies like insulin replacement therapy, insulin agonists like Trulicity
research into transplantation of pancreas (or just islet cells), vaccinations
describe type 2 diabetes
aka non-insulin-dependent diabetes mellitus
caused by insulin resistance, deficiency in response of beta cells in pancreas to glucose
what are some characteristics of type 2 diabetes?
insensitive to endogenous insulin
correlates with excess abdominal fat
inflated fat cells and over-nourished liver/muscle cells
hyperplasia of pancreatic beta cells (usually seen postmortem)
list some complications with type 2 diabetes
heart disease, stroke, kidney disease, eye problems, diabetic neuropathy and nerve damage (esp in feet), depression
what are natural methods of treating type 2 diabetes?
lifestyle changes, more exercise, controlled diet
describe the HPA axis
corticotropin-releasing hormone (CRH) —> adrenocorticotropic hormone (ACTH) —> cortisol from adrenal cortex
briefly describe the adrenal gland
medulla (inside) - produces catecholamines, epinephrine and norepinephrine
cortex (outside) - corticosteroids secreted from here, cortisol, aldosterone, androgens, etc.
what cells produce catecholamines in the adrenal gland?
chromaffin cells
