Endocrinology: anterior pituitary gland function (2a) Flashcards
Hypothalamopituitary axis
see diagram in notes
Hypothalamic hormones at the top
Anterior pituitary in the middle
Third gland below that
(Final target tissue at the bottom)
Explanation of diagram:
- dopamine inhibits prolactin production and PRH interferes with dopamine to allow prolactin (PRL) production.
- TRH (thyrotrophin releasing hormone) causes TSH production and enhances prolactin production
- CRH (cortico releasing hormone) causes ACTH (adrenal cortico hormone) affecting the adrenal glands
- GHRH (Growth hormone releasing hormone)
- & GHIH (growth hormone inhibiting hormone aka Somatostatin (ss)) control release of growth hormone
GnRH (gonadotrophin releasing hormone) released during pregnancy
Anterior pituitary hormones
Remember FLATPRoG
FSH (gonadotrophin)
LH (gonadotrophin)
ACTH (corticotrophin)
TSH (Thyrotrophin)
PRL (prolactin)
GH (somatotrophin)
*TSH, LH, FSH are glycoproteins. All 3 similar in structure. MW ~30 kDa.
Each has 2 sub-units: a units are similar, b confers specificity
*Control of LH/FSH secretion occurs via GnRH & mechanism for this differs between the sexes
Cells that produce hormones are often called –something related to that hormone-trophs
*LH/FSH secreted from gonadotrophs- because they release gonadotrophin
(see pregnancy lectures)
*TSH secreted from thyrotrophs - as they produce thyroid stimulating hormones
*Lactotrophs produce PRL (prolactin) causes milk production in humans and has other regulatory qualities in other organisms
*Somatotrophs produce growth hormones
Growth hormone
Growth hormone helps to reverse muscle wastage/ increase muscle vol in all age groups
Hence growth hormones are used to treat anorexia nervosa and muscle wasting in AIDS
It stimulates growth (in terms of build: height/bones) until end of puberty
Only human growth hormone has a direct effect on human growth other animal growth hormones such as those found in cows milk will not have the same effect.
HGH used to be collected for use from cadavers but is now synthetically produced – as using cadaver sourced HGH was linked to transfer of disease
- Major form 191aa, MW 22kDa.
- Shorter 20kDA variant (~10% of hGH).
GH has widespread effects
i)promotes growth of bone, soft tissue & viscera
ii)metabolic effects promoting aa uptake into muscle & breakdown of lipid to fatty acids for respiration. +insulin antagonist
Control of release
*This is mediated through GHRH (+)and somatostatin (inhibitory) which in turn are under CNS control
*Normally there is clear episodic secretion related to sleep-wake cycle with peaks occurring every 2-3 hours
first 2-3 years increasing maintained through childhood, peaking in puberty reducing and maintaining across adulthood then decreasing with age
Growth hormone secretions
*GH output increases with size to maintain the concentration of GH pulses needed to sustain growth during childhood
*Nutritional state is also a factor in GH secretion
*Many other hormones are involved in process of physical growth eg thyroxine, sex steroids
Long term side effects of growth hormone injections increases the risk of cancer
Why have inhibitory hormones?
Provides an extra layer of control
Allows for quick change
Particularly helpful in muscle function and aging
(see diagram)
endocrine control of growth
Growth depends on GH but is influenced by other factors such as:
-Genetics
- diet
-normal levels of other growth related hormones
- freedom from chronic disease and stressful environment
(I.e. Children abused or subject to trauma often do not grow as much as would be expected)
Further info on growth hormone function
*Promotes growth indirectly by stimulating liver’s production of somatomedins
(Somato = body medins = modulator)
*Primary somatomedin is insulin-like growth factor (IGF-1)
- Acts directly on bone & soft tissues- brings about most growth-promoting actions
- Stimulates protein synthesis, cell division, and lengthening and thickening of bones
*Exerts metabolic effects not related to growth
–Increases fatty acid levels in blood by enhancing breakdown of triglycerides stored in adipose tissue
–Increases blood glucose by decreasing glucose uptake by muscles
*The only way to take up GH supplements is via injection since GH is a peptide
Prolactin
*Prolactin is similar in structure to GH. Human Prl ~22kDA, 199 aa.
*Made by lactotrophs in the anterior pituitary
*Its primary role is to initiate and sustain lactation
*Prl is under inhibitory control of dopamine.
*It is released episodically and raised in pregnancy and lactation
*Dopamine limits prolactin so when dopamine drops prolactin levels rise resulting in TRH increase
*TRH causes an increase in thyroid hormones
*Excess PRL can cause infertility
*Prolactin may have a role in osmoregulation in other animals e.g. seagulls and fish
*Many drugs stimulate the secretion of prolactin due to their dopamine antagonist effects
*overproduction of prolactin leads to infertility and the ergot derivative bromocriptine has been used to treat this
*High levels of prolactin causes infertility by reducing the chance of successful ovulation bromocriptine reduces prolactin levels because it acts to increase dopamine levels
Hypothalamo pituitary adrenal axis
(see diagram)
*ACTH (adrenocortico releasing hormone) regulates the function of the adrenal cortex
*Has a crucial role in stimulation of glucocorticoid secretion in response to stress
*ACTH secretion controlled by CRH (cortico releasing hormone),
in turn under negative feedback control by cortisol.
*Its release is episodic and increased by stress
*Hydrocortisone creams used for eczema – acting as anti-inflammation/anti-stress agent
- Rats without a pituitary gland died when placed under stress in a test which normal healthy rats survived without side effects.
*Cortisone levels are highest 2hrs before waking
Pathology related to the anterior pituitary: oversecretion
Secretion biological definition = synthesis AND release
*Oversecretion often due to benign tumour; pituitary adenoma, may be functional or non-functional
*may occur spontaneously or as a result of lack of supression in hypothalamic trophic hormone
*Thats because increase in releasing hormone would cause hypertrophy and hyperplasia of the pituitary cells over time
*Pituitary adenoma tumours are treated with drugs or radiotherapy to shrink it and if this doesn’t work the tumour can be surgically removed through the nasal cavity
Symptoms:
-Anovulation can occur due to pituitary tumour
-Visual disturbances and headaches can also occur due to swelling pressing on ocular nerve
-Galactorrhoea may also occur – production of breast milk
GH Pathology: Oversecretion
*Overproduction of GH causes gigantism in young.
*After maturity over-production causes acromegaly – coarsening of features – bigger hands and face but no growth in height
Comparison of pattern of secretion of GH in normal subjects and patients with acromegaly and GH deficit
*The “normal” pulsatile secretion is lost in each of the abnormal states
Overproduction of gh in young people causes gigantism, causing broadening of the features as seen here being extremely tall or short can limit life expectancy
Pathology of pituitary hormone: undersecretion
Causes:
*Impaired secretion of hypothalamic hormones
–Direct effect on pituitary function (see connections in diagram below)
*disconnection of axis (tumour, trauma, infection)
*pituitary aplasia or hypoplasia
*pituitary destruction (tumour, surgery, infarction)
*irradiation
Effect of hormone loss/ deficiency:
*GH: deficiency in young can lead to dwarfism (if before puberty)
Pituitary dwarfism types:
- Glycopituitary dwarf –small but in proportion
- Achondroplasia – point mutation – proportion of limbs is different – limbs are shorter
- Primordial dwarfism – extremely small
*ACTH: causes adrenal insufficiency
*LH/FSH: leads to loss of reproductive function eg GnRH secretion vulnerable to calorie restriction, amenorrhoea (loss of period) seen in anorexics / over-trained athletes
*TSH: congenital deficiency rare but can be lost in congenital pituitary hypoplasia. Leads to symptoms of hypothyroidism: primary hypothyroidism : low TSH secretion secondary: low T1/T4 secretion
*Prolactin: no clinical symptoms associated with this. It is under inhibitory control so only lost following pituitary destruction.
