Hormones 3 & 4 Flashcards
what are the 2 key components of growth:
bone (height) and soft tissue (weight)
what is the continuous process of growth characterised by
spurts and ultimate arrest
what are the requirements for growth and their function
hormones - primarily growth hormone
decent diet - vitamins, minerals, energy, amino acids
extent of growth genetically determined
what happens in adolescence so that no further growth is possible
epiphyseal plate “closes” in adolescence
what is the function of chondrocytes and osteoblasts within different sections of the bone
top :
middle :
middle :
bottom :
top : diving chondrocytes add length to bone
middle : produce cartilage
middle : old (larger) start to disintegrate
bottom : is the osteoblasts, lay down bone on top of cartilage
what is the growth hormone release controlled by
GHRH and GHIH
what is pulsatile release
the circadian rhythm stress that causes the release growth of hormones
how many amino acid peptides within the growth hormone
191 amino acid peptides
how does the growth hormone atypically extend its half life
atypically has a plasma binding protein
what are the direct and indirect effects of growth hormone
D: on growth and metabolism
I: growth and
metabolism through stimulation of
insulin-like growth factor-1 (IGF-1), which is released from the liver
growth hormones release pattern
particularly high during sleep
describe the full effects of growth hormones function
stimulates differentiation of precursor cells in bone
(prechondrocytes → chondrocytes) – these produce IGF-1
*IGF-1 stimulates chondrocyte proliferation →new cartilage→new bone→ growth
*
where is GH and IGFs function
GH and IGFs stimulate protein synthesis in muscle and other tissues
IGFs : stimulate cell division
example of growth hormones cascade
GH stimulates cell maturation and IGF-1 production
then IGF-1 stimulates cell division and tissue growth
how do IGFs travel
as an auto/paracrine (local) & a hormone (travels in blood)
what are the effects of growth hormones GH metabolically
uptake of plasma amino acids (for protein synthesis)
- breakdown of fat (energy for growth)
- spares glucose stores (responsible hormone)
what are the effects of growth hormones, IGF-1 and insulin metabolically
uptake of plasma amino acids (for protein synthesis)
- glucose/energy substrate uptake into cells (for growth)
what are the effects of growth hormones, GH and IGF-1 together metabolically
together these hormones ensure tight regulation of energy reserves
what is the function of thyroid hormones in relations to growth
THs stimulate GH receptor expression
allows GH to have an effect, synthesis and regulation
anabolic, involved in synthesis reactions
what is the function of thyroid hormones in homeostasis
initiate changes in gene expression slowly
raises metabolic rate & produces heat
*provides substrates for oxidative metabolism (AA’s, FA’s & CHO)
what is the function of thyroid hormones in foetal brains
required for foetal brain development (deficiency = cretinism)
→ can be caused by dietary iodine deficiency in the mother
*important for nervous system function & cognition
role of insulin as a hormone
*required for growth
*enhances protein synthesis and amino acid uptake
*inhibits protein degradation
→ net increase in proteins
*promotes uptake of glucose into cells
*helps maintain energy balance
role of sex hormones
*co-ordinates pubertal growth spurt
*stimulate production of GH/IGF
*induce closure of epiphyseal plate (stops further growth)
*testosterone directly increases protein synthesis (anabolic steroids)
role of cortisol
Cortisol
*antagonistic in high concentration
*stimulates protein breakdown
*inhibits GH and growth processes
*arrests growth in favour of stress response
name the GH disorders
pituitary dwarfism, pituitary giant (gigantism), acromegaly
what causes Pituitary Dwarfism
childhood deficiency in GH, due to production/receptor problem
what is the course of treatment for Pituitary Dwarfism
treated using genetically engineered hGH
what are the limitations when treating Pituitary Dwarfism
*limited treatment window (before epiphyseal plate
closes)
what is the causes Pituitary Giant
childhood excess of GH caused by a benign, slow growing, GH-secreting anterior pituitary tumour
extensive growth of long bones – excessive height.
what is the course of treatment for Pituitary Giant
*treatment usually surgical removal of tumour
*alternatively can be treated with somatostatin-like drugs (inhibit GH release)
what is the causes Acromegaly
excess GH after epiphyseal plate closure caused by a benign, slow growing, GH-secreting anterior pituitary tumour
symptoms/features of acromegaly
*thickening of bones in hands, feet and head
(particularly the jaw)
*increased size of other soft tissues (e.g. heart) may
impair physiological function
what is the course of treatment for Acromegaly
*treatment usually surgical removal of tumour
*alternatively can be treated with somatostatin-like
drugs (inhibit GH release)
name the thyroid hormone disorders
hyperthyroidism vs hypothyroidism
- goiter
what type of hormone is the thyroid hormone
anterior pituitary hormone
describe thyroid gland a bit and where is it
bi lobed, 15-20g large gland at the base of throat
what is the thyroid gland made up of, name the 2 cell types and their function
2 endocrine cell types
follicular cells-secrete THs
clear (C) cells-secrete calcitonin
how the cells arranged within the thyroid gland
arranged in follicles
enclosed spherical structure
lined by follicular cells
what do the cells contain within the thyroid gland
contains colloid → sticky,
glycoprotein-rich matrix
where does TH synthesised from
tyrosine
is TH soluble in plasma and what are the implications
no it is not as it is lipophilic, hence require plasma binding proteins → thyroid-binding globulin (TBG
what is the half life of TH
T4 ~ 6 days; T3 ~ 1 day
how is T4 converted to T3
T4 converted to T3 in target tissue by tissue deiodinase (peripheral deiodination)
where does T4 usually form
in plasma
where are receptors for TH
receptors are intracellular, located in nuclei of most cells
how is the TH pieced together
remain attached to
thyroglobulin backbone
how is TH released and regulated
tonic release through hypothalamus- anterior pituitary-thyroid gland
through neg. feedback
what is hyperthyroidism caused by
Tumour, nodules, too much
symptoms of hyperthyroidsm
increased metabolic rate and heat production
→heat intolerance/weight loss
increased protein catabolism
→muscle weakness/weight loss
altered nervous system function
→hyperexcitable reflexes and psychological disturbances
elevated cardiovascular function
→increased heart rate/contractile force
causes of hyperthyroidism
*hormone-secreting thyroid
tumour (rare) or nodules
*Graves’ disease (antibodies
produced that bind and activate the thyroid gland
treatment for hyperthyroidism
*surgical removal of part of gland
*radioactive iodine treatment (destroys TH-producing follicular cells)
*thyrostatics (block TH synthesis)
*propylthiouracil (blocks T4 → T3)
how to identify Thyroid Hormone Dysfunction - Goiter
significant enlargement
of the thyroid gland
*a mass such as this is termed a goiter
how are goiters formed
goiter formation is caused by trophic action of TSH on
thyroid follicular cells
→results in hypertrophy (overgrowth) of thyroid gland
causes of Hypothyroidism
deficiency in dietary iodine
*autoimmune attack of thyroid gland
Hypothyroidism treatment
*oral thyroxine (T4)
*dietary iodine supplements e.g.
iodized salt
key symptoms/features of Hypothyroidism
decreased metabolic rate and heat production
→cold intolerance/weight gain
disrupted protein synthesis
→brittle nails/thin skin
altered nervous system function
→slow speech/reflexes, fatigue
reduced cardiovascular function
→ slow heart rate/weaker pulse
what are TSIs and what is their function
TSIs- trophic so stimulate thyroid overgrowth
Thyroid stimulating immunoglobulins (TSIs) mimic actions of TSH by binding it’s receptors and stimulating thyroid gland
causes Graves’ disease
what is exophthalmia
immune-mediated
enlargement of eye muscles/tissues
function of the adrenal medulla
rapid stress response – “fight or flight
electrolyte balance
minor role in development of sexual characteristics
identify the 3 layers of adrenal cortex
➢glucocorticoids (cortisol)
➢adrenal androgens (low affinity)
➢mineralocorticoids (e.g. aldosterone) → renin-angiotensin release system
function of adrenal cortex
layers and steroid biosynthesis
what is hypercortisolism also known as
also known as Cushing’s syndrome
hypocortisolism causes and alternative name
adrenal insufficiency/Addison’s disease
what is the adrenal gland composed of
medulla and cortex
key feature of medulla and cortex
medulla is neurohormonal and cortex is true endocrine
where does the medulla arise from and what do they produce
arises from neural tissue
produces catecholamines (adrenaline)
~ ¼ of total mass
where does the cortex arise from and what do they produce
arises from non-neural tissue
produces steroid hormones
cortisol, aldosterone and androgens
~ ¾ of total mass
physiological effects of fight or flight response in adrenal medulla
→ glycogen breakdown
rapid glucose source
→ fat breakdown
more energy available
→ increased cardiac function
→ increased ventilation
all support/maintain physical activity
composition of adrenal cortex
divided into 3 histological sections which produce distinct types of
steroid hormones
*not entirely exclusive, some cross over exists
adrenal cortex : where are all steroid hormones synthesised from
*steroid hormones all synthesised from cholesterol via complex biosynthetic
pathway
what does Steroid biosynthesis in the adrenal gland mean and involve
biosynthesis involves complex chemical modifications to cholesterol
what are the 3 layers of the adrenal cortex and what type of hormones are in each
Zona glomerulosa: outside: Adrogens and sex hormones
Zona fasciculata: cortisol
Zona reticularis: inside : aldosterone
what are Glucocorticoids
group of steroid hormones
what is a primary Glucocorticoids
cortisol is the primary glucocorticoid and is vital for survival
function of Glucocorticoids
strong diurnal rhythm of secretion → inducible in response to stress
what does cortisol (Glucocorticoids) production show
cortisol production shows a circadian pattern
patterns change in
response to physical
and psychological
stress
what does ACTH bind to and to relase what effect
ACTH binds membrane-bound receptors on cells of Zona fasciculata in the adrenal cortex
increases conversion of cholesterol→ cortisol
what is cortisol used for
critical, long-term mediator of stress response
→ adrenalectomized animals die in response to stress
*protects against hypoglycemia (opposes insulin) and has both catabolic and
anabolic actions
which is faster cortisol response or catecholamine stress response
cortisol actions much slower (60-90 mins) than catecholamine stress response (secs)
metabolic functions of cortisol
1.stimulates gluconeogenesis
2.breaks down fat and uses fatty acids/breaks down protein into amino acids for use as energy sources
3.maintains plasma glucose levels and prevents hypoglycemia
4.mobilises energy to cope with, adapt to or escape stress
Metabolic Functions of Cortisol: what does stimulates gluconeogenesis allow for
protects carbohydrate stores (glycogen) – eye on the long term
- can build-up or breakdown glycogen stores depending on stress levels
Metabolic Functions of Cortisol: what does breaks down fat and uses fatty acids as energy source allow for
alternative to glucose
Metabolic Functions of Cortisol: what does breaks down protein into amino acids for use as an energy source allow for
another alternative to glucose
- these amino acids are also used for gluconeogenesis
function of cortisol in other systems :Brain function
mood regulation
learning and memory
function of cortisol in other systems : Development
important for proper develop
function of cortisol in other systems : how does the system comprise others to allow stress response
Other
reduces “non-essential” function
e.g. growth, reproduction
in favour of responding to stress
function of cortisol in other systems: Suppresses inflammatory &
immune response
prevents harmful over-reaction
what other systems does cortisol impact
brain, development, immune system
what are the function of low affinity androgens
converted to testosterone or estrogen
from low activity to more potent sex steroids in other tissues
Adrenal Androgens: function of estrogen and testosterone
development/maintenance of male/female sexual/reproductive characteristics
Mineralocorticoids function
regulate minerals e.g. Na+ and K
by alter gene expression → increased expression of Na+ transporter proteins
*thereby influences levels of Na+ (and water) reabsorbed by the kidney
example of mineralocorticoids and Glucocorticoids
M: aldosterone
G: cortisol
describe mineralocorticoid receptors compared to adrenal androgens and Glucocorticoid receptors (cortisol )
G: membrane bound steroid recepors
A: low activity of androgens at receptors
M: steroid receptors (intracellular)
chexck later
what is the aldosterone release controlled by
aldosterone release: where is the renin released from and what is it stimulated by
from kidney cell
decrease blood volume (haemorrhage, dehydration)
▪ increase Na+ levels
→ detected by specialised sensor cells in kidney
aldosterone release: what does the renin release result in
results in angiotensin II production
→ binds receptors on surface of zona glomerulosa cells
→ activates biosynthesis of aldosterone
3 key Hypercortisolism causes
1.Primary hypercortisolism
2. Secondary hypercortisolism
3. Iatrogenic (physician-caused) hypercortisolism
Hypercortisolism causes: Secondary hypercortisolism
excessive ACTH (trophic hormone) production
pituitary tumour that secretes ACTH and stimulates too much cortisol
Hypercortisolism causes: PRIMARY hypercortisolism
adrenal glands (TUMOUR)
produces too much cortisol
Hypercortisolism causes: Iatrogenic (physician-caused) hypercortisolism
- occurs following glucocorticoid therapy for other conditions
- glucocorticoids are commonly used topical and systemic anti-inflammatory drugs
hypercortisolism treatment
surgical removal of tumour
* removal of glucocorticoid therapy – must be gradual to allow axis to adapt
what happens biologically during Hypercortisolism (Cushing’s syndrome)
diabetagenic (hyperglycemia) → too much glucose in blood
* tissue wasting → muscle, fat and bone breakdown (breakdown of proteins/fat
key symptoms of hypercortisolism
“plumping” of trunk and “moon face” → redistribution of fat
*mood disorder/immunosuppression/impaired inflammatory cascade
name 2 key causes of Hypocortisolism
1.primary adrenal insufficiency (at level of adrenal gland
2.Secondary adrenal insufficiency (at level of anterior pituitary trophic hormone)
causes of Hypocortisolism: primary adrenal insufficiency
loss of adrenal cortical function (up to 90% loss before symptoms apparent)
* can be caused by tuberculosis, invasive tumours, autoimmune attack, genetic disease
* sufferers at severe risk of “Addison’s crisis” following minor stress/illness
→ no cortisol → profound hypoglycemia → potentially fatal
causes of Hypocortisolism: secondary adrenal insufficiency
pituitary disease → ACTH deficiency
* symptoms less dramatic – aldosterone not affected (not dependent on ACTH)
treatment for Hypocortisolism
daily oral administration of glucocorticoids and mineralocorticoids
* careful dietary/fluid management
* treatment of causative disorder
