Cell Signaling/Endocrine Flashcards
describe the three major types of signaling and give a biological example of each
paracine signaling: signaling molecules target adjacent cells
synaptic signaling: signaling molecules (NT) diffuse across synapse to neuron (ACH –> NMJ)
endocrine signaling: signaling molecules travel long distances via bloodstream (hormone)
what determines if a hormone will bind to an intracellular vs cell surface receptor
- size
- solubility
what do kinases and phosphatases do?
kinases: enzymes that add a PO4 3-
phosphotases: enzymes that remove PO4 3-
define affinity.
how does KD relate to affinity.
the likelihood of something going to bind. 1/KD is the affinity. The lower the KD the higher the affinity.
define specificity.
binds only one or a specific family of ligands
define saturability.
how many receptors are bound by a ligand
define law of mass action
[L] + [R] –> [LR] –> biological response
can ion channels activate intracellular mechanisms?
yes
give examples of cell surface receptors
- ligand gated ion channels (nAChR)
- G protein coupled receptors (mAChR, GnRH-R)
- serine/threonine receptors (TGFbeta R)
- tyrosine kinase receptors (Insulin R)
what type of hormones bind to cell surface receptors
protein, peptide and fatty acid derived hormones; large, water soluble
also catecholamines
are cell surface receptors or intracellular receptors faster?
cell surface receptors
give examples of intracellular receptors
- nuclear receptors
- mineralocorticoid receptor
what type of hormones bind to intracellular receptors
steroids, amino acids, thyroid hormones (small, lipid soluble)
what can cell surface receptors do
protein transport, protein synthesis, secretion, ion channels, and gene expression
name two receptors that bind the same ligand
nAChR and mAChR
describe adrenergic receptors (alpha 1, alpha 2 and beta) in regard to their G protein and intracellular/biological response
alpha 1 - Galpha q/11, increases Ca+2, smooth muscle contraction
alpha 2 - Galpha i, inhibits cAMP, smooth muscle contraction
beta - Galpha s, increases cAMP, heart muscle contraction, smooth muscle relaxation and glycogenolysis
describe muscarinic receptors (1,3, & 5 and 2,4) in regard to their G protein and intracellular response
M1,3,5 - Galpha q/11, increase Ca2+ & MAP kinases
M2,4 - Galpha i, inhibits cAMP
what determines if there is a biological response to a hormone
- specificity
- affinity
what are the major classes of hormones
- protein/peptide hormones
- fatty acid hormones
- steroid hormones
- modified amino acids
how is diabetes an L vs R problem?
type 1 diabetes - no beta cells of pancreas so no production of insulin (L problem)
type 2 diabetes - dysfunctional insulin receptors (R problem)
what do intracellular receptors do?
regulate gene transcription
what describes a hormones interaction with a nuclear receptor?
slow
dimerized HR act as transcription factor
what is the importance of the hypothalamic pituitary vascular system
hypothalamus has portal system with anterior pituitary (two capillaries); hypothalamus synthesizes/secretes neurhormones to AP and AP releases trophic hormones into blood stream to target organs
how does the hypothalamus send hormones to the posterior pituitary
through neurons, they originate in hypothalamus and axons terminate in posterior pituitary
where are gonadotropes located and what do they secrete
anterior pituitary
LH/FSH
where are thyrotropes located and what do they secrete
anterior pituitary
TSH
where are somatotropes located and what do they secrete
anterior pituitary
Growth Hormone
where are corticotropes located and what do they secrete
anterior pituitary
ACTH
where are lactotropes located and what do they secrete
anterior pituitary
prolactin (Prl)
what cell types are in the posterior pituitary and what hormones do they release
neurons
oxytocin & vasopressin/ADH
Peptide Hormones
solubility:
receptor:
precursor(s):
examples:
solubility: soluble
receptor: cell surface receptors
precursor(s): preprohormone (ER) & prohormone (vesicle)
examples: hypothalamic releasing hormones, pituitary hormones, GI/pancreatic hormones, calcitonin, PTH
Fatty Acid Hormones
solubility:
receptor:
precursor(s):
examples:
solubility: soluble
receptor: cell surface receptors
precursor(s): *phospholipids + *phospholipase –> *arachidonic acid + *cyclooxygenase (COX) –> eicosanoids
examples: prostaglandins, prostacyclins, leukotrienes, thromboxanes
Steroid Hormones
solubility:
receptor:
precursor(s):
examples:
solubility: insoluble
receptor: intracellular receptors
precursor(s): cholesterol & pregnenolone
examples: glucocorticoids, mineralocorticoids, testosterone, estrogen, vitamin D3
Amino Acid Derived Hormones
precursor(s):
examples & their receptors
precursor(s): tyrosine
examples:
T3/T4 (intracellular R, insoluble)
catecholamines (E/NE) (cell surface receptor)
Calcitonin
source:
main effect:
source: parafollicular cells of thyroid gland (primary) & GI/lung tissues
main effect: decreases calcium in blood via
1. inhibits osteoclasts (suppressing resorption) & increasing Ca deposition in bones
2. inhibits tubular reabsorption of Ca & PO4 3- so increase Ca loss in urine
Parathyroid Hormone
source:
main effect:
source: chief cells of parathyroid gland
main effect: increases blood calcium via…
1. tubular reabsorption of Ca in kidney
2. vitamin D production from kidney increases Ca absorption in SI
3. osteoclast resorption
describe primary and secondary hyperparathyroidism
primary: excess PTH from parathyroid gland = demineralization of bone
secondary: excess Ca loss from renal disease = stimulates PTH
what are the calcium pools (calcium storage)
- intracellular Ca (available for signaling, enzyme activation & muscle contraction)
- blood & ECF (unavailable for function bc bound to protein)
- bone (majority unavailable)
what are the calcium organs
- kidney
- small intestine
- bone (major)
vitamin D3
source:
main effect:
source: stimulated by PTH in the distal tubule of kidney
main effect: increases blood [Ca2+] via…
1. increasing calbindin so SI can increase its absorption
2. initiates transcription for bone to release Ca2+ and PO4 3- via mineralization
describe the pathway of inactive and active vitamin D3
sunlight –> liver (inactive) –> kidney (active)
describe glucose regulation
insulin (from beta cells) decrease blood glucose by transporting glucose into fat/muscles and store as glycogen
glucagon (alpha cells) increase blood glucose by increasing glycogenolysis and gluconeogenesis
differentiate between adenohypophysis and neurohypophysis
adenohypophosis: anterior pituitary origin from oral ectoderm from roof of mouth
neurohypophysis: posterior pituitary origin from neural tissue from floor of diencephalon
what is the 2 cell 2 gonadotropin theory in the ovary?
LH stimulates theca cells are to synthesize androgens and FSH stimulates granulosa cells to convert androgens to estrogen
distinguish different components of male and female reproductive tract
testes –> epididymis –> wolffian duct (vas deferens) –> urethra
ovaries –> mullerian duct (uterine tubes) –> uterus –> cervix –> vagina
in males what does the external genitalia and prostate gland need?
conversion of testosterone —> DHT via 5alpha-reductase
in males what does the internal reproductive tract depend on
testosterone and AMH
where is sperm produced? where do they mature?
where is T produced?
produced in seminiferous tubules
mature in epididymis
interstitial space
what is required for spermatozoa development
counter current heat exchange
what transporters transport glucose into muscle and fat cells
what is it dependent on
what organs are they not in
GLUT4
insulin-dependent
NOT in brain or liver
what species is diabetes mellitus more present in?
pathophysiology?
middle/older aged dogs/cats (female dogs more likely than males)
obesity, chronic inflammation, amyloid deposition in islets (cats) and viral infection
Oxytocin
effect?
regulation?
effect: milk ejection, uterine smooth muscle contraction, maternal behavior
regulation: stimulated by physical & psychological stimuli; inhibited by catecholamines (stress)
Vasopressin/Antidiuretic Hormone (ADH)
effect?
regulation?
effect: increases water reabsorption by increasing the amount of aquaporin channels in the collecting tubule which increases BP/BV and decreased urine output
regulation: stimulated by increased plasma osmolarity and decreased BP/BV; inhibited by alcohol, increased BP/BV, or decreased plasma osmolarity
when is ADH secreted?
before thirst
contrast central diabetes insipidus vs nephrogenic diabetes insipidus
DI: deficiency in ADH
central: no ADH from posterior pituitary
nephrogenic: kidney not responding to ADH due to renal disease or VP receptor/ aquaporin mutation
Prolactin
cell that secretes it:
stimulation:
inhibition:
effects:
cell that secretes it: lactotropes
stimulation: suckling
inhibition: dopamine
effects: mammary gland growth, stimulates lactogenesis, and stimulates gene transcription that encode milk proteins
describe the hypothalamic-pituitary-thyroid axis
TRH (hypo)
TSH (AP)
T3/T4 (thyroid gland)
T3 primary effects
increase BMR, development of fetal/neonatal brain, stimulates growth
T3 secondary effects
increased heart rate, cardiac output/contractility, vasodilation, CNS/mental state (anxiety/depression), increased GFR, and reproduction/fertility negatively impacted
hyperthyroidism
symptoms:
treatment:
more common in:
primary:
symptoms: weight loss, angry, anxious, increased appetite
treatment: elimination of thyroid gland, radioactive I131, or inhibit thyroid perioxidase
more common in: cats
primary: benign, hyperplastic thyroid tissue
hypothyroidism
symptoms:
treatment:
more common in:
primary, secondary, tertitary:
symptoms: obesity, poor coat, lethargy, cold
treatment: supplements of I, T3, or Selenium
more common in: dogs
primary, secondary, tertitary: thyroid disease/iodine deficiency, TSH problem, TRH problem
describe the hypothalamic-pituitary-adrenal axis
CRH (hypo)
ACTH (AP)
cortisol (adrenal cortex)
what is the precursor for ACTH
POMC
what is the transport protein that binds cortisol to plasma proteins
transcortin
what zone produces mineralocorticoids
zona glomerulosa (outer layer)
what zone produces glucocorticoids
zona fasiculata (middle layer)
what zone produces sex steroids
zona reticularis (inner layer)
what are the effects of cortisol
1.metabolism: increased gluconeogensis, mobilize aa, inhibit glucose uptake, increase fat breakdown
2. antiinflammatory/ immunosuprresive
3. other: fetal development of type 2 alveolar cells, cognitive function, fear, bone formation, wound healing, Ca absorption
what are the effects of aldosterone (mineralocorticoid)
stimulates transcription of Na/K ATPase Pump = increase Na reabsorption and K secretion in kidney
stimulated by increase in EC [K] and angiotensin II
hyperadrenocortisim
cortisol levels:
effect on CRH and ACTH:
primary:
iatrogenic:
cortisol levels: high
effect on CRH and ACTH: decreased due to (-) feedback
primary: pituitary dependent (excess ACTH) or adrenal tumors
iatrogenic: excess glucocorticoid therapy
hypoadrenocortism
cortisol levels:
effect on CRH and ACTH:
primary:
iatrogenic:
cortisol levels: low
effect on CRH and ACTH: increased
primary: injury to adrenal gland tissue, infection or autoimmune
iatrogenic: discontinuation of corticosteroid therapy
growth hormone
hypothalamic hormone:
anterior pituitary cell type:
stimulation:
inhibition:
direct growth effects:
indirect growth effects:
metabolic effects:
hypothalamic hormone: GHRH
anterior pituitary cell type: somatotropes
stimulation: ghrelin (stomach)
inhibition: somatostatin
direct growth effects: liver, differentiation of chondrocytes
indirect growth effects: bone, muscle, adipose, proliferation of chondrocytes/muscle growth
metabolic effects: protein anabolism, fat catabolism, carb metabolism
pituitary dwarfism
lack of all pituitary hormones (GH, TSH, ACTH)
giantism
excess GH from birth before epiphyseal closure (swelling, enlarged peripheral nn, delayed puberty, hypogonadotropic hypogonadism)
acromegaly
late onset excess GH due to GH secreting pituitary tumor (organ hypertrophy or bony changes, insulin resistance, *male cats)
describe the female hypothalamic-pituitary- gonadal axis
GnRH (hypo)
LH and FSH (AP gonadotropes)
Estrogen & Inhibin (theca and granulosa cells)
what is the dominant follicle first to have/do
dominant follicle first to express LH receptor and produce inhibin
what causes ovulation
dominant follicle produces large amounts of estrogen resulting in an LH surge (+) feedback, this LH surge results in release of the follicle
what subunit do gonadotropes and thyrotropes share?
they share the alpha glycoprotein subunit (alpha-GSU)
differ in beta subunits
what produces the large amount of progesterone during the estrous cycle
the corpus lutea (yellow body)
describe the follicular phase
- egg w/ cohort of follicles present and produce FSH to stimulate follicle growth
- domintant follicle has LHR and produces inhibin to prevent recruitment of additional follicles
- dominant becomes mature and produces E and Inhibin
- large amount of E = LH surge
- LH results in release of follicle from ovary
describe the luteal phase
- formation of corpus luteum produces P and E, and inhibin
- if no pregnancy, PGF2alpha-MRP = death to CL and resets
- P and E decrease, LH/FSH increase
what day does ovulation begin in animals
day zero
what hormone does the pre-ovulatory follicle secrete
estrogen
what are the effects of estrogen
follicle growth
secondary sex characteristics
growth/proliferation of epihelial lining of repro tract
feedback to brain
inhibits milk production
what are the effects of progesterone
prepares endometrium from embryo implantation
breast growth
negative feedback to brain
inhibits milk production
inhibits myometrial contractions
most common birth defect of male genitalia
cryptochordism
effects of testosterone
stimulate spermatogenesis
maintain wolffian duct/accessory glands
external genitalia, secondary sex characteristics
stimulate metabolism
affect CNS function/behavior
