endocrinology Flashcards
GAP junction method of communication/ specificity dependence
cell-cell
depends on location
synaptic method of communication/ specificity dependence
across synaptic cleft
location/ receptor dependent
para/auto crine method of communication/ specificity dependence
interstitial fluid
receptor dependent
endocrine method of communication/ specificity dependence
body fluid circulation
receptor dependent
non-classical endocrine tissues
heart
kidney
platelets
endothelium
WBC
adipocytes
hormone characteristics
high affinity > effective at low conc
synergistic > combined effect
antagonistic> can oppose actions of other
competitive
permissive > presence required for others to work
classes of hormones
steroid
peptide
amino acid
steroid hormones
synthesised from cholesterol
small/ hydrophobic/ released immediately following synthesis/ circulate in bound form/ bind to hormone response elements to intiate gene txn/ slow, long-lasting effects
peptide hormones
synthesised from amino acids
3-332 amino acids long
synthesised by preprohormones
stored prior to release
act on cell surface receptors via 2nd messenger systems
amino acid hormones
synthesised from tyrosine
stored for instant release
different modes of action
2nd messengers
CAMP
Ca2+
cGMP
diacylglycerol
IP3
3rd messenger
protein kinase
hormone release mechanisms
continuous
pulsatile
circadian
exocytosis on stimuli
post-release modification examples
steroids > oestrogen from androgens
vitamin D
angiotensinogen»_space; angiotensinogen II
epinephrine/ norepinephrine action
cause vasoconstriction/ vasodilation via B2 receptors mediating smooth muscle relaxation via cAMP pathway
Methods of controlling hormone effects
modification
degradation
receptor down-regulation
termination of intracellular effects
negative feedback
hypothalamic-pituitary axis
site of interaction between endocrine and nervous systems, exerting control over endocrine glands
posterior pituitary
neural origin
neurohypophis
axons/ nerve endings from neurones in hypothalamus
anterior pituitary
Rathke’s pouch
adenohypothesis
endocrine tissue
p pituitary hormones
- produced in magnocellar neurones of hypothalamus and stores in pp
ADH
oxytocin
oxytocin
uterine smooth muscle contraction
breast myoepithelial contraction
ADH
kidney water retention
hypothalamic hormones
released into portal circulation > act on pituitary
release hypophosiotrophic hormones
TRH/ GnRH/ CRH/ GHRH/ GH inhibiting/ dopamine
TRH
thyrotropin releasing
acts on thyrotrophs
stimulates TSH/ prolactin release
GnRH
gonadotropin releasing acts on gonadotrophs
stimulates FSH/ LH
CRH
corticotrophin acting on corticotrophs
stimulates ACTH/ prolactin
GHRH
growth hormone releasing acting on somatotrophs
stimulates GH release
GH inhibiting hormone
acts on somatotrophs
inhibits GH/Gastrin/VIP/glucagon/insulin
dopamine
acts on lactotrophs
inhibits prolactin release
a pituitary hormones
released into systemic circulation
controlled by hypothalamic hypophysiotropic hormones
TSH/FSH/LH/ACTH/GH/Prolactin
TSH
thyrotroph acting
stimulates thyroid hormone release
FSH
gonadotroph acting
sex steroid production stimulation
LH
gonadotroph acting
sex steroid production stimulation
ACTH
corticotroph acting
stimulates cortisol release
GH
somatotroph acting
stimulates growth
prolactin
lactotroph acting
stimulates milk production
growth hormone
somatotropin
191 amino acid peptide hormone
somatotroph synthesised in a pituitary
responds to GHRH from hypothalamus
stimulates growth/ cell reproduction/ regeneration
direct/ indirect via IGF1
IGF1
insulin-like growth factor
direct acute metabolic actions of GH
promotes glyconeogenesis
decreased glucose metabolism/ cell uptake
promotes IGF1 production
long term growth hormone via IGF-1
growth-promoting action on bone/ epiphyseal cartilage/ soft tissue/ gonads/ viscera
promotes amino acid uptake/ protein synthesis
insulin-like endocrine effect on tissues
thyroid gland regions affected
growth and development (foetal neural development/ bone growth)
metabolic (^BMR)
cardiovascular (^cardiac output)
neurological (emotional tone, ^alertness/memory/reflexes/wakefulness)
thyroid major product
T4/ thyroxine
most physiologically active thyroid hormone
T3/ triiodothyronine
thyroid products
T3/ T4
calcitonin
calcitonin
Ca homeostasis
thyroid structure
2 lobes w interconnecting isthmus
2 pairs parathyroids on rear
follicle functional units
single cell layer surrounding colloid pool
colloid pool
production/ storage of hormones
calcitonin secreting cells
C cells
thyroid hormone production mechanism
at apical follicular membrane, Tyr residues in thyroglobulin iodinated in presence of thyroperoxidase
T1/T2 precursors coupled under thyroperoxidase control
thyroglobulin
glycoprotein synthesised by follicular cells and released into follicular lumen via exocytosis
3 major thyroid transporting hormones
thyroxine-binding globulin
thyroxine binding prealbumin
albumin
thyroxine binding globulin
70% T3/T4
thyroxine-binding prealbumin
10-15% T4
albumin
15-20% circulating T3/T4
rapid dissociation makes major source of free hormone to tissues
thyroid hormone release mechanism
hypothalamus releases TRH on ap
releases TSH to blood
thyroid releases thyroid hormones
negative feedback by T3/T4
TSH effect on thyroid
increases iodide uptake/ hyroglobulin synthesis/ iodination of thyroglobulin/ pinocytosis of colloid/ lysosomal activity/thyroid cell size
thyroid hormone metabolism
80% plasma T3 derived from peripheral metabolism of T4 > deiodination to produce active/ inactive T3
enzymes controlling local control of thyroid hormones
type 1 deiodinase > active/ inactive T3
“ 2 active T3
“ 3 inactive T3
T1/ T2 deiodinase action
act on outer ring of T4
active T3
T1/3 deiodinase action
act on inner ring of T4
inactive T3
4 thyroid hormone receptors
alpha 1/2
beta 1/2
TR a2 doesn’t bind T3
rest have higher affinity for T3 than T4
T3/ T4 deiodinase action
heat production
^ MBR/lipolysis/cardiac output
kidney structure
cortex:
zona glomerulosa (outer)
zona fasiculata (middle)
zona reticularis (inner)
medulla
cortex percentage adrenal weight
80-90%
zona glomerulosa
outer
15% cortical volume
produces aldosterone
lacks 17 a-hydroxylase
zona fasiculata
middle
large, lipid-containing cells
75% cortical volume
produces cortisol/ androgens
zona reticularis
inner
compact cells w less lipid
10% cortical volume
produces cortisol androgens
medulla
10-12% adrenal weight
epinephrine major product
specialised
sympathetic system
aldosterone
major mineralocorticoid
50-70% bound to albumin in plasma
15-20 min half-life
primary action on kidney/ colon/ salivary glands
maintain [Na+]/ extracellular fluid volume
binds to mineralocorticoid receptors in principal cells
upregulates/ activates Na+/K+ ATPase
fasiculata and reticularis enzyme absence and consequence
both lack CYP11B2
therefore no aldosterone produced
cortisol location
half-life
> 90% bound to plasma proteins in blood
bind to receptor for gene transcription
60-90 min half-life
cortisol effects
stimulates hepatic gluconeogenesis/ muscle catabolism
inhibits glucose uptake in muscular and adipose tissue/ bone formation/ gonadal release of testosterone, oestrogen and progestins
anti-inflammatory/ immunosuppression
collagen/ connective tissue loss
^ vascular sensitivity to epinephrine/ norepinephrine
modulate behaviour and cognitive function
anti-inflammatory/ immunosuppression
inhibits cytokine production/ prostaglandin and leukotriene production
testes function
spermatogenesis
secretes large amount of androgens and small amounts of oestrogens
ovaries function
oogenesis
secretes large amount of oestrogens/ progesterone and small amount of androgens
oogenesis
oocytes developed in developing ovary and arrest in prophase on meiosis 1, existing in primordial follicles
ovarian cycle
oocyte maturation and ovum release
28 day cycle in line w uterine as part of menstrual cycle
phases of ovarian cycle
follicular phase
ovulation
luteal phase
follicular phase
maturation of follicles
several months
1. pre-antral phase
2. antral phase
3. pre-ovulatory phase
ovulation phase
inflammatory event
eroding wall of ovary and follicle
oocyte, sona pellucida and corona radiata required for capture by fimbriae and movement through oviduct
luteal phase
corpus luteum develops over 14 days in ovary
granulosa cells fill w lipid
progesterone ^ and oestrogen decreases due to LH surge
corpus luteum in event of no pregnancy
develops into corpus albicans
oestrogen/ progesterone levels drop
allows FSH/LH to surge
corpus luteum in event of pregnancy
placenta releases human chorionic gonadotrophin, enabling corpus luteum to persist
pre-antral phase
paracrine factors stimulate growth
antimillerian hormone limits number developing at same time
antral phase
fluid-filled atria appear
zona granulosa layers ^
thicker zona pellucida
theca interna more apparent
FSH aids growth
dominant follicle selected and becomessignificant steroidogenic gland
theca
catalyze androgen production from cholesterol
granulosa
contain aromatase so convert androgen to oestrogen
pre-ovulatory phase
graafian follicle responds to LH surge by completing 1st meiotic division, arresting in meiosis II metaphase > haploid secondary oocyte and polar body
^FSH/LH / enzyme expression in granulosa cells promoting progesterone production
theca/ granulosa release inflammatory cytokines and hydrolytic enzymes
GnRH release
pulsatile
high frequency > LH
low frequency > FSH
FSH
stimulates recruitment and growth of immature follicles
upregulates aromatase gene expression/ activity
induces LH receptor expression in granulosa cells
prevents apoptosis of antral follicles
LH
acts on theca cells in follicles, promotes androgen production
surge triggers ovulation
acts on granulosa cells to secrete progesterone
maintains corpus luteum
oestrogens
prepares reproductive tract for potential fertilisation
dominant hormone secreted pre-ovulation
progesterone
promotes uterine secretions for potential fertilisation/ implantation
dominant post-ovulation
inhibin A/ B
secreted from granulosa cells, inhibits FSH secretion
insufficient growth hormone condition
hypo-pituitary dwarfism
excessive growth hormone in early life condition
pituitary gigantism
excessive GH secretion in adulthood condition
acromegaly
enlarged jaw, hands and feet
hypothyroidism in children symptoms
decreased growth and mental capacity
hypothyroidism in adults symptoms
lethargy, bradychardia, weight gain, mental slowness, depression
hypothyroidism treatment
levothroxine/ T4
hyperthyroidism symptoms
weight loss
tachycardia
heat intolerance
tremors
graves disease
cause of thyrotoxicosis
autoimmune condition in which antibodies stimulate TSH receptor
symptoms of graves disease
eyelid retraction
eye muscle swelling in orbit
goitre
goitre
enlarged thyroid due to overstimulation
Addisons disease
adrenocorticoid insufficiency
80% autoimmune
20% result of infection, malignancy or medication
cortisol deficiency symptoms
weakness
fatigue
decreased appetite
hypoglycemia
mineralocorticoid symptoms
dehydration
hyponatraemia
hyperkalemia
acidosis
hypotension
cushing’s syndrome
chronic cortisol excess
commonly iatrogenic/ resulting from pituitary/adrenal abnormality
Cushing’s disease
pituitary tumour
cushings symptoms
weight gain
hypertension
osteoperosis
thirst/ polyuria
psychological disturbances
epidermis atrophy
