Endocrine control of growth Flashcards
Where does growth hormone come from?
Pituitary glands
Where do adrenal hormones come from?
Suprarenal glands just above the kidneys
What is the pancreas made up of?
99% exocrine tissue, 1% endocrine tissue
What does the pancreas secrete?
Digestive enzymes into second part of duodenum
including insulin and glucagon
Where is the pituitary gland?
Just anterior to and below hypothalamus
Infundibulum
Stalk connecting hypothalamus and pituitary gland
Within which bone is the pituitary gland located?
Sphenoid bone
Sella turcica
= pituitary fossa
Diphragma sella
Dura mater covering pituitary fossa
Parts of pituitary
Posterior: directly connecting to brain through infindibulum - pars nervosa (nervous)
Anterior - pars distalis (upgrowth from pharynx) - secretory tissue - adenohypothesis
Intermediate: pars intermedia
2 connections between brain and pituitary
Portal system (blood connections)
Nerve fibres in pituitary(distal axon terminations in hypothalamus)
-send connections (small peptide hormones) to posterior pituitary
Portal system
Set of capillaries in brain and pituitary
Metabolic rate
Total body energy expenditure per unit time
Basal metabolic rate (BMR)
Metabolic rate when at mental and physical rest but not sleeping, at comfortable T and fasted for at least 12 hours
Calorigenic effect
Hypothalamus senses certain external T
Anterior pituitary releases TSH
Carriers carry TSH round body, most notably in thyroid
Releases thyroid hormones (T3 and T4)
Increases body T when released into blood
Thyroid hormones
T1 - monoiodothyronin -1 iodine
T2 - 2 iodine
T3 - trioiodothyronin - 3 iodine
T4 - T4
Thyroid hormones (T3 and T4) stimulate:
Thyronine - T3 and Thyroxine - T4
- protein synthesis
- > used of glucose and free fatty acids for ATP production
- > lipolysis
Which effects of thyroid hormones are similar to other endocrine hormones?
Insulin and growth hormones convert aas to proteins
Glucagon and growth hormone turn lipids into ffa and liberate glucose from glycogen
Which effects of thyroid hormones are similar to other endocrine hormones?
Insulin and growth hormones convert aas to proteins
Glucagon and growth hormone turn lipids into ffa and liberate glucose from glycogen
If too little thyroid hormone throughout life
Cretinism
- congenital: hypothyroidism
- mentally immature, cannot hear or speak
- bone growth retarded
- sexually immature
Too little thyroid hormone as adult
Myxoedema
- adult hypothyroidism
- low TSH or low T3 and T4
- low cardiac output - oedema
Hyperthyroidism
Graves disease
- HR high
- Autoimmune disease - antibodies ‘mimic’ TSH
- x10 females
- pressure behind eyes causes exophthalmus
Goiter
Large thyroid gland
A lot of iodine accumulated in neck
Can happen in hypo or hyperthyroid conditions or euthyroidism
Usually attributed to low dietary intake of iodine
Adrenal glands
Ad - secretory Embedded in perinephric fat Has its own blood supply from aorta Attached to top of each kidney Made up capsule (dense irregular CT) Hylus, cortex (secretory tissue), medulla (sympathetic ganglion pulled out of place)
Layers of cortex
Zona glomerulosa - cells tend to form balls
Zona fasciculata
Zona reticularis
Medulla
Produces Adr and Noradr
Homeostatic control of adrenal
CRH (hormone from hypothalamus)
Goes through portal system into anterior pituitary
Anterior pituitary releases ACTH
Goes into blood around body attaches to receptors on adrenal gland –> produces cortisol
Elevated levels of cortisol
As they rise, release of supplying hormone (CRH) is switched off and vice versa
Mineralcorticoids - zona glomerulosa
Produces aldosterone
- regulates homeostasis of sodium and potassium ions
- aldosterone secretion stimulated by dehydration, sodium deficiency or loss of blood
- starts biochemical cascade called Renin-Angiotensin-Aldosterone pathway (RAA)
- returns blood pressure, volume and sodium concentration to normal
Glucocorticoids - zona fasciculata
Cortisol:
Gluconeogenesis produces aas, ffas, lactic acid
Reduce inflammation - useful in treatment of rheumatoid arthritis
Depress immune system - used as immunosuppressors post transplant
Cushing’s disease
Result of excess cortisol caused by > ACTH
Occurs as result of tumour on pituitary gland or adrenal cortex
Causes oedema, hyperglycaemia, muscle wastage and makes px vulnerable to infection
-very rounded body with spindly limbs
Adison’s disease
Underactive adrenal cortex Deficits in glucocortisoids and mineralocorticoids Weight loss Drop in glucose and sodium levels Hypotension Changes in skin pigmentation
Androgens - zona reticularis
Secretes dehydroepiandrosterone (DHEA)
- in females - promotes libido and DHEA converted into oestrogens
- also an androgen: in male and female - axillary and pubic hair growth
Virilism
Female looks like man
Small opening of vagina
Enlarged clitoris
Actions of catecholamines - adrenal medulla
Effects mediated through alpha or beta adrenoreceptors
Complex - multiple types of receptor and multiple tissues and cells
Generally noradrenalin stimulates a> b
Generally adrenalin stimulates both a and b
Excitation (a1 and b1)
> rate and force of contraction of heart muscle
Constriction of BVs
metabolic rate (inc. breakdown of glycogen to produce glucose)
Inhibition (a2 and b2)
Dilation of BVs and bronchioles
Relaxation of smooth muscle
Reduced activity of digestive and urinary organs
Stress
3 phases in response to stress:
- alarm phase
- resistance phase
- exhaustion phase
Alarm phase
- ‘fight or flight’ initiated - impulses from hypothalamus to sympathetic NS
- glucose and O2 - skeletal muscles and heart
- nonessential body functions (digestive, urinary and reproductive)
- blood flow to kidneys stimulates RAA pathway
Resistance phase
Initiated by hypothalamic releasing hormones - long lasting response
Exhaustion phase
Prolonged exposure to hormones in resistance phase causes:
- muscle wastage
- suppression of immune system
- ulceration of GI tract
- failure pancreatic cells
Nuclei in thalamus
60-70
Collections of nerve cell bodies within CNS
e.g.oxytocin neurosecretory cell (sends connections to posterior pituitary)
Oxytocin and ADH neurosecretory cells
Send small peptide hormones to posterior pituitary
Peptide hormones manufactured in cell bodies of these neurosecretory cells
Transported down axons with carrier molecule (neurothycin) to distal axon through infundibulum into pars nervosa where it sits waiting to be released
Release of peptide hormones from pars nervosa
Separates from neurothycin, goes into bloodstream, acts around body where target receptors are
ADH and ocytocin mainly
ADH and oxytocin
Very small peptide hormones (8-9 amino acids)
Manufactured in hypothalamus in body of nerve cell, transported with carrier molecule down to pars nervosa, released from neurohypothesis
Oxytocin acts on
Smooth muscle e.g. uterus
ADH
Vasopressin
Goes to kidneys
Prevents diaduresis
Helps to recover water
How does hypothalamus connect to pituitary
Nerve tracts
hypothalamohypothesial tracts
How many capillaries between blood leaving heart and returning to heart in pituitary
2
portal system
Portal system
Releasing hormones released from cells in the nuclei of hypothalamus
These go into blood of this portal system (capillaries)
That blood drains down into anterior pituitary
Releasing hormones act on cells in pituitary to release other hormones
Other hormones go into blood and around body
e.g. follicle stimulating hormone, growth hormone
Components of growth hormone system
Pituitary gland Thyroid Parathyroid Adrenal Islets of Langerhans Placenta Endocrine cells of the gut Pineal Liver Testes/ ovaries
Anterior pituitary/ adenohypophysis secretes
Growth hormone Prolactin Thyrotrophin Follicle stimulating hormone Luteinizing hormone
Neurohypophysis secretes
Oxytocin
How does growth hormone act on the body?
Stimulates growth and replication
Increases rate of protein synthesis
Most cells responsive, but especially skeletal muscle, cartilage and bone
Indirect mechanism of action of growth hormone
Acts on liver to produce synthesis and release insulin-like growth factors (ICFs)
ICFs are peptides that bind to receptors and > uptake of aa and protein synthesis
Skeletal muscle is example of target tissue
Rapid action that is particularly effective after meal (when aas and glucose are available)
Direct mechanism of action of growth hormone
Selective actions that occur after aas and glucose levels in blood have returned to normal
GH stimulates stem cells to divide in epithelia and CTs
Somatomedins (ICFs) stimulates later growth of daughter cells
In adipose tissue GH stimulates breakdown of stored triglycerides
As ffa levels rise many tissues stop using glucose and breakdown ffas for ATP - ‘glucose sparing’
In liver GH stimulates glycogenolysis
Since most tissues are using ffas for energy levels of glucose in blood are elevated - ‘diabetogenic effect’
Glucose sparing
As ffa levels rise many tissues stop using glucose and breakdown ffas for ATP
Diabetogenic effect
Since most tissues are using ffas for energy levels of glucose in blood are elevated
Control of growth hormone production
Stimulated by GH releasing hormone Inhibited by GH inhibiting hormone Both from the hypothalamus Somatomedins stimulate GHIH Somatomedins inhibit GHRH
Too much growth hormone: gigantism
Excessive growth of long bones muscles and internal organs
Robert Wadlow - 9lb at birth, 8 ft 11 inches
Too much growth hormone: acro- (terminally) megaly- (enlargement) - primary effects
Enlarged hands, feet, lower jaw, skull, clavicle and internal organs
Secondary effects of acromegaly
Compression of portal system-diminished dopamine leads to excess prolactin
Oestrogen and testosterone deficiency - lack of periods, loss of libido, loss of facial hair in men
Deficiency in thyroid stimulating hormone - weight gain, lethargy
Deficiency in adrenocorticotrophic hormone -lack of cortisol can be fatal
Treatment for too much growth hormone
Radiotherapy
Somatostatin (GHIH) analogues
GH receptor antagonists
Transsphenoidal surgery
Too little growth hormone: pituitary drawfism
Weight and height normal at birth until 12 months
Can be caused by traumatic birth, meningitis, tumour or inheritance
Insulin-like growth factor 1
Skeletal effects
Fat
> cartilage formation and skeletal growth
Lipolysis
Anti-insulin actions
Extra skeletal effects
Carbohydrate metabolism
>protein synthesis and cell growth and proliferation
> blood sugar levels
Insulin and glucagon vs growth hormone: secreted by
I&G: Secreted by alpha and beta cells in pancreas
GH secreted by anterior pituitary
Insulin and glucagon vs growth hormone: release controlled by
I&G: release controlled by glucose levels in blood
GH: release controlled by glucose levels in blood and by levels of GH and somatomedins in blood
I&H vs GH: influence by hypothalamus
I&G: release not directly under influence of hypothalamus
GH: release directly influenced by hypothalamus
I&G vs GH: what promotes conversion of aas and protein
I&G: insulin
GH: growth hormone
I&G vs GH: what liberates glucose from glycogen
I&G: glucagon
GH: growth hormone
I&G vs GH: what breaks down adipose tissue into ffas?
I&G: glucagon
GH: growth hormone
I&G vs GH: involvement in skeletal growth
I&G: not directly involved
GH: > cartilage formation and skeletal growth
What is insulin
Peptide hormone
Secreted by beta cells of islets of Langerhans
Inactive precursor called proinsulin
Packed into vesicles by Golgi apparatus
Stimulus for release of insulin
> blood glucose
> blood arginine/ leucine
Type 1 diabetes/ insulin dependent diabetes mellitus
Lack of insulin from beta cells
Cells can’t take-up glucose (body reacts as if glucose levels are low - lipids and proteins broken down and ketone bodies produced - can cause ketoacidosis > death)
High glucose levels in urine - polyuria (sweet!)
Chronic hyperglycaemia and dehydration causes many problems e.g. fatigue, muscle wasting, neuropathy, retinopathy
Type 2 diabetes/ Non-insulin dependent diabetes mellitus
Typically obese individuals >40
Maturity onset diabetes
90% of diabetes cases
Insulin levels normal but peripheral tissues don’t respond
< weight and metformin (which lowers glucose synthesis and release at liver)
Metformin
An oral hypoglycaemic agent of the biguanide group
Half-life of about 3 hours
Lowers blood sugar by means that are incompletely understood
Causes > in glucose uptake by muscle
< hepatic production of glucose
Does not cause hypoglycaemia but prevents hyperglycaeia
Unwanted effects include GI disturbances and lactic acidosis
Diabetes insipidus
Posterior pituitary gland fails to produce adequate levels of ADH
Results in polydipsia (excessive drinking) and polyuria (excessive urination) - i.e. symptoms of diabetes
Polycystic ovarian syndrome (PCOS)
20% of women have cysts
6-10% have PCOS
Major feature of PCOS is insulin resistance accompanied by hyperandrogenism
Reduced fertility
