endocrine - Feb 27th to 29th Flashcards
Where is calcium found?
- bones
- soft tissues (intracellular and extracellular)
What is calcium stored as in bones? What is it made up of?
hydroxyapatite (calcium salts + phosphate)
How do you calculate total body calcium?
intake (diet) - output (kidneys)
What 3 hormones regulate movement of calcium between bone, kidneys, & intestine?
- Parathyroid hormone (PTH)
- Calcitriol (vitamin D3)
- Calcitonin
(1 & 2 most important in adults)
What is PTH? (3)
- secreted continuously by the parathyroid gland
- helps to regulate calcium
- essential for life (cannot be removed)
What are the 2 types of parathyroid gland cells?
- Chief cells (produce PTH)
- Oxyphils (function unknown)
What plasma Ca2+ falls, how does PTH get it back to normal?
- Stimulates osteoclasts to resorb bone (primary mechanism)
- Stimulates kidneys to resorb Ca2+
- Stimulates kidneys to produce enzyme needed to activate vitamin D,
which promotes better absorption of Ca2+ from food/drink across
intestinal epithelium
What is Hypocalcaemia? How is it corrected?
- Plasma calcium too low
- ↑ PTH secretion (stimulates resorption to get more Ca2+ back into blood)
What is Hypercalcaemia? How is it corrected?
- Plasma calcium too high
- ↓ PTH secretion
Describe the process of bone deposition and reposition
Bone deposition:
- Osteoblasts secrete a matrix of
collagen protein, which becomes
hardened into deposits of
hydroxyapatite
Bone resorption:
- Osteoclasts dissolve
hydroxyapatite & return the bone
Ca2+ (& phosphate) to the blood
Describe the process of vitamin D synthesis
- Vitamin D3 produced
from it’s precursor
molecule, 7-
dehydrocholesterol
under the influence of
UVB sunlight - Vitamin D3 secreted
into blood from
skin/intestine (functions
as a pre-hormone i.e.
inactive) - Vitamin D3 pre-hormone goes to liver & is chemically changed (hydroxyl group added
to C25) - Requires hydroxyl
group addition to C1
to become active
(done by enzyme in
kidneys that is
stimulated by PTH) - Active vitamin D can then stimulates intestinal absorption of Ca2+, and directly stimulates bone resorption by promoting formation of
osteoclasts
How is vitamin D synthesized in human?
- Synthesized from 7-dehydrocholesterol with UV light in skin + obtained from dietary sources
- Those far from the equator don’t have enough sunlight, so they need to ingest it via diet or suppliments
How is vitamin D synthesized in dogs and cats?
haha tricked you, it can’t be synthesized – only from diet
What is Calcitonin?
- Made in C cells of thyroid in response to high Ca2+
- Thought to only play minor role in adult humans (thyroidectomy patients are not hypercalcaemic)
How is phosphate metabolism regulated?
by the same mechanisms that
regulate Ca2+ metabolism (but not as tightly) – return/receive
phosphate to/from bone, kidney filtrate, & GI tract
Describe Hyperparathyroidism (5)
- Parathyroid too active
- Hypercalcaemia (too much
Ca2+ in blood) - Increased bone resorption
(fractures) - Mineralization of soft tissues
- Increased thirst & urination
(Ca2+ blocks ADH effects)
Describe Hypoparathyroidism (4)
- Parathyroid not active enough
- Hypocalcaemia (not enough
Ca2+ in blood) - Muscular weakness, ataxia
- Cardiac arrhythmias
Describe vitamin D deficiency (differences between adults and children, etc.)
Results in poor bone mineralization
In children = Rickets
* Bone pain, stunted growth, deformities
In adults = Osteomalacia
* Bone pain, fractures
Describe Osteoporosis (and its risk factors/treatments)
- Most common disorder of bone
- Reduction of bone quality due to excess absorption
- Risk of bone fractures
Known risk factors:
- Sex (females,
especially after menopause)
- Lack of exercise
- Calcium deficient diet
Treatment:
- Adequate calcium & vitamin D intake
- Hormone therapy, PTH, calcitonin (may be associated with cardiovascular disease, stroke, cancer)
- Exercise
- Best treatment is prevention!
What is the Somatotropic Axis?
- GH secretion inhibited by
somatostatin from hypothalamus - GHRH stimulates GH secretion from anterior pituitary
- GH has many targets (direct
or through stimulation of liver’s production of somatomedins e.g. IGF-1)
What is Growth Hormone / GH (Somatotropin)?
- Synthesized, stored, & secreted by somatotropic cells in the lateral wings of the anterior pituitary gland
- Most bound to binding protein (GHBP) but may be transported
as free hormone - Most abundant anterior pituitary hormone
- Plays an important role in growth
Describe GH secretion patterns (very brief)
- Occurs in peaks/pulse
- Largest GH peak occurs ~1 hr after
onset of sleep (circadian rhythm) - Basal levels highest early in life
What factors decrease GH secretion?
- Hyperglycemia
- Glucocorticoids
- Endocrine disruptors
What are Somatomedins?
Insulin-like growth factors
Describe Somatomedins (mostly just IGF-1)
- GH acts on the liver to produce IGFs (IGF-1, IGF-2)
- IGF-1 almost entirely bound to transport proteins (IGF-BPs)
- Some IGF-1 transport/binding proteins have an endocrine
function (i.e. there are receptors for these proteins) - GH stimulates the synthesis/release of IGF-1 in other tissues
besides the liver i.e. it is difficult to differentiate between direct
actions of GH & IGF-1 - GH & IGF-1 appear to exert opposite actions in some tissues,
suggesting independent roles
Describe the metabolic effects of GH (what does it act on and what do it do to it)
Liver:
- stimulates IGF-1to trigger bone/cartilage growth and protein synthesis in organs
Adipose Tissue:
- lipolysis
- release of fatty acids
Most other tissues:
- decreased glucose use
Basically, GH plays an especially important role in endocrine regulation of growth (muscle & bone)
What does Hypertrophy refer to (concerning GH)
increased cell size
What does Hyperplasia refer to (concerning GH)
increased cell number
What are the two types of bone growth, and what do they do?
Bone diameter increase:
* Growth occurring around the bone
* Matrix deposits on the outer surface of bone
Bone length increase:
- Growth occurring at epiphyseal plates (near end of bone)
- Epiphyseal plate contains chondrocytes (columns of collagen-producing cells)
- As collagen layer thickens, old cartilage calcifies & chondrocytes
degenerate
- Osteoblasts invade & lay bone matrix on top of cartilage base
What disease(s) appear in growing animals with GH under-
production/decreased
sensitivity?
Pituitary Dwarfism: small size,
juvenile proportions, normal shape at maturity but stunted
Pygmies (Laron-Type Dwarfism): decreased responsiveness to GH
(receptor deficiency)
What disease(s) appear in adult animals with GH under-
production/decreased
sensitivity?
Acromegaly: thickening of bones/joints & skin, enlargement of internal organs (tongue, liver, spleen)
What disease(s) appear in growing animals with GH over-production?
Pituitary Gigantism
What disease(s) appear in adult animals with GH over-production?
Alopecia (dogs): thin skin, hair loss (poodles)
Cushing’s Syndrome: increased cortisol inhibits GH synthesis
What’s a GH-related disorder in humans caused by severe GH or (GHR) deficiency in children?
Dwarfism
What’s a GH-related disorder in humans caused by over secretion of GH in children
Gigantism
What’s a GH-related disorder in humans caused by Severe GH or (GHR) deficiency in adults?
Acromegaly (lengthened jaw, coarse facial features, growth of hands & feet)
What is rHGH Treatment?
- Used to treat children with short
stature (bottom 1% on growth charts) - Daily injections for ~2 years increased their height by 1.3”
- $22,000/year cost
- Side effects: glucose intolerance, pancreatitis, & psychological problems surrounding height
What are the causes of disproportioned miniature, dwarf, and teacup cats?
Miniature:
* Selective breeding
Dwarf:
* “Munchkin” genetic mutation
* Chondrodysplasia, short-legged
Teacup
* Dwarf breed, normally proportioned
* Severe delay in growth may cause bone, muscle, & other endocrine problems
What is Ateliotic (caused by pituitary dwarfism in dogs)?
- GH deficiency, uniformly small body
- Most “toy” breeds (Chihuahuas, Boston Terriers, Italian Greyhounds, Maltese, Miniature Pinschers, Miniature Spaniels, Pomeranians, Toy Poodles, Yorkies, etc.)
What is Micromelic (caused by pituitary dwarfism in dogs)?
- Short legs
- Basset Hounds, Bulldogs, Corgis, Dachshunds, Lhasa Apsos, Scottish Terriers, Shetland Sheepdogs, etc.
What is Brachycephalic (caused by pituitary dwarfism in dogs)?
- Shortened skull bones & short muzzle (e.g. Boxers)
What cells are the testes made up of?
- Sertoli cells
- Leydig cells
What do Leydig cells do?
secrete testosterone
What do Sertoli cell do?
support sperm
What hormones play a role in the male Hypothalamic-pituitary-
gonadal axis?
- GnRH = gonadotropin releasing
hormone secreted into portal vessels - FSH = follicle stimulating hormone
(gonadotropin) - LH = luteinizing hormone
(gonadotropin) - Testosterone will travel to other
target cells, resulting in development
of secondary sex characteristics
Describe the negative feedback that occurs in the male Hypothalamic-pituitary- gonadal axis? (there are 3 main ways, hint: they involve testosterone and inhibitin)
- Testosterone inhibits GnRH secretion from hypothalamus
- Testosterone inhibits the anterior pituitary’s response to GnRH
- Sertoli cells secrete Inhibin which inhibits the anterior pituitary’s secretion of FSH without affecting LH
Describe testosterone, and its roles
- Secreted by the Leydig cells, located between seminiferous tubules
Testosterone in the fetus:
- Masculinizes tract & external genitalia
Testosterone during puberty & adulthood:
- Growth, maturation, & maintenance of male reproductive system
- Libido
- Secondary sex characteristics (hair growth, voice, skin, body shape)
- Bone, muscle
- Brain (behaviour, cognition)
How do anabolic steroids cause infertility?
- Mimic the effects of testosterone
- Excess testosterone shuts down pathway
- Testes stop producing sperm
- Testes stop producing testosterone
- Decreased libido & fertility
What are the 3 layers of the uterus (from outside to inside)?
- Perimetrium (outer, connective tissue)
- Myometrium (middle, smooth
muscle) - Endometrium (inner, epithelial)
Describe the hypothalamic-pituitary-gonadal axis in females
- hypothalamus produces gonadotrophin-releasing hormone (GnRH)
- GnRH stimulates anterior pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- FSH and LH act on the ovaries to produce oocytes and sex hormones (estrogen and progesterone)
What are Overt mensus?
endometrial spiral
arteries responsible for menstrual
bleeding (humans, apes)
What are Covert mensus?
endometrium is shed
without bleeding due to lack of
endometrial spiral arteries (dogs, cats)
What is the ovarian cycle?
Series of changes in the ovary where
the follicle matures, the ovum is shed, & the corpus luteum develops
What is the uterine (menstrual) cycle?
Series of changes in hormone
production & the structures of the
uterus & ovaries that make pregnancy possible
Which occurs first, uterine (menstrual) cycle or the ovarian cycle?
sike, they both happen at the same time :D
What happens in Stage 0 (just before day 1) of the ovarian/menstrual cycle?
HPG axis:
- gonadotropin secretion from anterior pituitary increases
Ovaries:
- FSH influences several ovarian follicles to begin maturation
Uterus:
- day 1 of menstrual bleeding begins
What happens in Stage 1 (Follicular Phase) of the ovarian/menstrual cycle?
HPG axis:
- Early: estradiol increases frequency of GnRH pulses
- Late: increase in FSH & LH (cumulates in LH surge)
Ovaries:
- Slight decline in FSH secretion but increased sensitivity (due to estradiol), LH & estradiol increasing
- Early: Some primary follicles grow, develop vesicles, & become secondary follicles
- Late: 1 follicle in 1 ovary reaches maturity (Graafian follicle)
Uterus:
- Estrogen stimulates endometrial growth
What happens is Stage 2 (Ovulation) of the ovarian/menstrual cycle?
- Requires an LH surge, stimulated
by increase in estradiol - Mature (Graafian) follicle grows
under FSH stimulation & ruptures - Secondary oocyte & surrounding
cells released & swept into uterine tube - Tissue left behind forms corpus luteum
What happens is Stage 3 (Luteal Phase & Menstruation) of the ovarian/menstrual cycle?
HPG axis:
- Early: Corpus luteum produces progesterone & estradiol resulting in negative feedback on HPG axis (decrease in FSH & LH, halting development of new follicles)
- Late: negative feedback removed, FSH & LH increase
Ovaries:
- Early: LH stimulates development of corpus luteum which secretes estradiol & progesterone, FSH & LH secretion then declines
- Late: corpus luteum regresses, decrease in estrogen & progesterone
Uterus:
- Early: endometrium anticipating pregnancy, progesterone causes cervical mucosal barrier to thicken
- Late: endometrium requires progesterone, otherwise vascular contracts & dies, sloughs off, & menstruation begins
What are the 3 phases of cyclic changes the endometrium goes through? When do they happen? What are their characteristics?
Proliferative phase:
- Occurs during follicular phase
- Increased estradiol stimulates growth of endometrium
Secretory phase:
- Occurs during luteal phase
- Increased progesterone from corpus luteum stimulates development of uterine glands
- Endometrium grows in thickness due to estradiol & progesterone
Menstrual phase:
- Result of decrease in ovarian hormone secretion during late luteal phase
- Necrosis & sloughing of endometrium
Starting at 1 day after
the LH peak (follicular phase), basal
body temp sharply rises…which hormone causes this?
progesterone
How do birth control pills work?
- Synthetic estrogen & progesterone
- Elevation of these ovarian hormones (due to the pill), leads
to negative feedback inhibition of gonadotropin secretion, so
ovulation never occurs - Simulates a false luteal phase
What is menopause?
- At menopause, ovaries depleted of follicles & stop secreting
estrogen (i.e. change at ovarian not pituitary level) - Weak form of estrogen made in adipose tissue (women with
more adipose tissue have higher levels of estrogen & are at
less risk of osteoporosis) - Menopause associated with increased risk of osteoporosis,
hot flashes, & aging
What is current thinking on menopause studies (estrogen and progesterone supplementation)?
Bad! The risks outweigh the benefits (great risk of cancer, cardiovascular issues and strokes)
What are the components of The Melanocortin System (13 components from POMC)?
4 posttranslational peptides:
- α-MSH, β-MSH, γ-MSH, ACTH
5 melanocortin receptors (7-membrane, G-coupled protein receptors):
- MC1R, MC2R, MC3R, MC4R, MC5R
2 melanocortin antagonists:
- Agouti, AGRP
2 proteins that modulate melanocortin activity:
- Mahogany, syndecan-3
1 opioid peptide (product of POMC but not part of melanocortin system)
- β-endorphin
What’s the role of the Melanocortin System?
- Posttranslational processing of POMC is tissue-specific
- Different POMC peptides produced by different cell types
- Control of range of many physiological functions by same
prohormone - Mutations in POMC gene/processing rare but possible
What does α-MSH do?
- α-MSH produced in brain inhibits food intake (mutation here results in early onset diabetes)
- α-MSH produced in skin acts on melanocytes, and contain melanin/pigment which influence human skin colour & rodent
coat colour (mutation here results in altered pigmentation)
How does α-MSH increases dark pigment in skin?
- α-MSH binds MC1R
- Activates signal pathways
(G-protein-coupled
receptors, cAMP, PKA,
CREB) - Synthesis of MITF
(microphthalmia-associated
transcription factor) - Transcription of Tyr & DCT
which influence
pigmentation
What is the role of MCR?
MCR is produced in adrenals, skin, brain, penis, etc. (penile MCR mutation associated with sexual function/dysfunction)
What is the role of the Agouti protein?
- Agouti protein is an antagonist to MCR1 in the skin (results in yellow pigmentation)
- Agouti protein is an antagonist to MCR4 in the brain (results in overeating & obesity; model for adult-onset obesity, hyperglycemia, & insulin resistance)
Why are Black Jaguars black?
They have a condition
known as melanism
(dominant gene mutation
in MC1R)
What causes red hair?
Results from 2 copies of
a recessive mutation in
the MC1R protein
What causes Erectile Dysfunction? How is it treated?
- Linked to MC4R
mutations (α-MSH analogs used to
treat erectile dysfunction; e.g. Melanotan II)
