Endo- physiology Flashcards
where is insulin initially synthesised in the cell
rough endoplasmic reticulum of pancreatic beta cells as preproinsulin
what happens to preproinsulin in the RER
converted into proinsulin
what are the components of proinsulin
A chain
B chain
connecting (C) peptide
which bonds form between the A and B chains of proinsulin
disulphide bonds
where is proinsulin converted to mature insulin
Golgi apparatus and secretory granules
what is the only cell in the body that makes insulin
beta-cell
how does glucose enter pancreatic beta cells
through the GLUT2 glucose transporter
what enzyme phosphorylates glucose in beta cells
glucokinase
what are islets of langerhans
clusters of ~1000 endocrine cells in the pancreas
3 main types of islet of langerhans cells
beta cells
alpha cells
delta cells
what do beta cells secrete
insulin
what do alpha cells secrete
glucagon
what do delta cells secrete
somatostatin
in T2DM, the number of secretory granules per beta cell is increased/reduced?
reduced- degranulation
action of glucagon
acts on the liver to promote hepatic glucose production, raising blood glucose
what is the incretin effect
greater increase in insulin production in response to oral glucose than in response to IV glucose
what is the principle incretin hormone
GLP-1
what does GLP-1 do
increases glucose-induced insulin release by beta cells
promotes beta cell proliferation
suppresses glucagon secretion at high levels
where is GLP-1 secreted from and where
secreted from gastrointestinal L-cells
in response to eating
Can GLP-1 stimulate insulin secretion without glucose?
no, it only acts in the presence of a depolarising glucose stimulus
through which receptor type does GLP-1 signal
a G protein-coupled receptor, using cAMP as a second messenge
which hormone is secreted by the hypothalamus to initiate thyroid hormone production
TRH (thyrotropin-releasing hormone)
what does TRH stimulate in the anterior pituitary
TSH (thyroid stimulating hormone)
what intracellular signalling pathway is activated by TSH binding
activation of G proteins, leading to conversion of GTP to GDP and production of cAMP
what is the role of cAMP in thyroid cells
stimulates production and release of T3 and T4
what is one major physiological effect of thyroid hormones
increased basal metabolic rate
thyroid hormone production is regulated through positive/negative feedback?
negative feedback
what is the structural unit of the thyroid gland and what are found inside these units
the thyroid follicle
colloid inside
what cells are found between follicles and what do they secrete
parafollicular (C) cells
secrete calcitonin
what are the two main thyroid hormones
T3 (triiodothyroninenine) and T4 (thyroxine)
what percentage of thyroid hormone secretion is T4 and T3
T3- ~10%
T4- ~90%
what thyroid hormone is more biologically active T4/T3
T3- 4x more potent
where is T4 converted to T3
in the liver and kidneys
in plasma, what percentage of T3 and T4 is protein bound
> 99%
what are the main thyroid hormone-binding proteins in plasma
thyroxine-binding globulin ~70%
thyroxine-binding pre-albumin ~20%
albumin ~5%
which hormone, T3 or T4, binds less strongly to plasma proteins
T3
what form of thyroid hormone enters cells
only the free (unbound) form
which conditions increase TBG levels
pregnancy
oral contraceptive pill
chronic active hepatitis
biliary cirrhosis
which conditions decrease TBG levels
androgens
cushings syndrome
severe systemic illness
chronic liver disease
how many transmembrane regions do G-protein coupled receptors have
7
what are the 10 major endocrine glands
pituitary
hypothalamus
pineal
thyroid
parathyroid
thymus
adrenals
pancreas
ovary
testes
which endocrine gland provides the highest level of endocrine control
hypothalamus
what do pancreatic alpha cells do when blood glucose levels are high
decrease glucagon secretion
what hormones are released during stress and exercise
cortisol and adrenaline
what processes do cortisol and adrenaline stimulate in the liver
gluconeogenesis and glycogenolysis
what are the 3 classes of hormones
steroids
amine-derived
peptide
what are steroid hormones derived from
cholesterol
are steroid hormones hydrophilic or hydrophobic
hydrophobic (lipid-soluble)
what is the role of cortisol and where is it secreted from
plays a roll in mediating stress responses
secreted from adrenal cortex
what is the role of testosterone and where is it secreted from
responsible for male sexual characteristics
secreted from gonads
what is the role of oestradiol (oestrogen) and where is it secreted from
responsible for female sexual characteristics
secreted from placenta
examples of steroid hormones
cortisol
osterogen
testosterone
what are amine-derived hormones derived from
amino acids
are most amine-derived hormones hydrophobic or hydrophilic
hydrophilic
where are amine-derived hormones secreted from
thyroid gland
adrenal medulla
are steroid hormones stored in the body
no, once synthesized, they are secreted immediately and are not stored.
How are steroid, amine-derived, and peptide hormones transported in the blood?
steroid- bound to carrier proteins
amine-derived- unbound (free)
peptide- unbound (free)
how are amine-derived hormones like adrenaline stored in the body
vesicles in cytoplasm
examples of amine-derived hormones
adrenaline
thyroid hormones
are peptide hormones hydrophobic/hydrophilic
hydrophilic
what type of hormone account for the majority of hormones produced in the body
peptide hormones
where are peptide hormones secreted from
pituitary
parathyroid
heart
stomach
liver
kidneys
examples of peptide hormones
oxytocin
ADH
growth hormone
insulin
where is the ‘command centre’ of the endocrine system
hypothalamus-pituitary complex
what are the two main gonadotrophin hormones
FSH
LH
what does FSH do in males and females
males- stimulates spermatogenesis in the testes
females- stimulates growth of ovarian follicles, stimulates ovary to secrete oestrogen
what does LH do in males and females
males- stimulates the testes to secrete testosterone
females- triggers ovulation, triggers progesterone production
what is the role of GnRH (gonadotrophin releasing hormone)
it stimulates the release of FSH and LH from the anterior pituitary
where is GnRH synthesised and released from
from GnRH neurone in the hypothalamus
How does the pulsatility of GnRH differ between males and females?
males- pulses at constant frequency
females- pulses vary during menstruation cycle
what regulates GnRH pulsatility
osteogen
progesterone
testosterone
how long does the follicular phase typically last
14 days +/- 7 days
how often are GnRH pulses during the early follicular phase
about every 1-2 hours
how often are GnRH pulses during the luteal phase
about every 4 hours
what do high-frequency GnRH pulses stimulate
stimulate LH release
what do low-frequency GnRH pulses stimulate
stimulate FSH release
what effect does high oestrogen have on GnRH
increases GnRH pulsatility, promoting LH surge
what effect does progesterone have on GnRH
reduces frequency of GnRH pulsatility
