Hypothalamic Pituitary Axis Flashcards
Describe the location of the pituitary gland
Pituitary gland sits beneath the hypothalamus in a socket of bone called sella turcica
State the embryonic source of pituitary gland development
- Anterior pituitary gland derived from primitive gut tissue
- Posterior pituitary gland derived from primitive brain tissue
- Connected to hypothalamus through infundibulum (pituitary stalk)
State the hormones synthesised in the hypothalamus and pass to posterior pituitary
Oxytocin, antidiuretic hormone
How are posterior pituitary hormones made and secreted
- Oxytocin and antidiuretic hormone secreted from posterior pituitary but synthesised by neurosecretory cells in the supraoptic and paraventricular nuclei of hypothalamus
- Transported down nerve cell axons to posterior pituitary
- Stored and released from posterior pituitary into circulation (neurocrine secretion)
State the role of oxytocin in the body
- Stimulus of sucking transmitted from breast to hypothalamus, resulting in release of oxytocin
- Oxytocin travels to mammary glands and causes lactation
- During childbirth, stimulus of pressure on cervix and uterine wall transmitted to hypothalamus
- Release of oxytocin stimulates powerful uterine contractions
Explain the role of ADH in the body
- Antidiuretic hormone (vasopressin) - reduces urine production
- When produced, increase permeability of collecting duct by inducing translocation of aquaporin to allow water retention
- § Alcohol inhibits ADH release - increased urination and dehydration
How do hormones secreted in hypothalamus reach anterior pituitary
- Hormones synthesised in hypothalamus travel down axons and stored median eminence before secreted into hypophyseal portal system (neurocrine function)
- These hormone stimulate or inhibit target endocrine cells in anterior pituitary gland
What are tropic hormones
Hormone involved in control of 2nd hormone
State the tropic hormones produced by hypothalamus and its function
- TRH - thyrotropin releasing hormone - stimulates TSH
- PRH - prolactin releasing hormone - stimulates prolactin
- PIH - prolactin inhibiting hormone (dopamine) - inhibit prolactin
- CRH - corticotropin releasing hormone - stimulate ACTH
- GnRH - gonadotropin releasing hormone - stimulate LH and FSH
- GHRH - growth hormone releasing hormone - stimulate growth hormone
- GHIH - growth hormone-inhibiting hormone (somatostatin) - inhibit growth hormone
State the hormones produced in anterior pituitary and their functions
- TSH - thyroid stimulating hormone - stimulates secretion of thyroid hormone from thyroid gland
- ACTH - adrenocorticotropic hormone - stimulate glucocorticoid (cortisol) secretion from adrenal cortex
- LH - luteinising hormone - ovulation and secretion of sex hormones
- FSH - follicle stimulating hormone - development of eggs and sperm
- PRL - prolactin - mammary gland development and milk secretion
- GH - growth hormone - growth and energy metabolism, stimulate IGFs
Describe the different negative feedback loops for anterior pituitary hormones
- Ultra short loop - tropic hormone to hypothalamus
- Short loop - anterior pituitary hormone to hypothalamus
- Direct long loop - endocrine gland hormone (eg. cortisol, IGF, thyroxine) to anterior pituitary
- Indirect long loop - endocrine gland hormone to hypothalamus
Where is IGF (somatomedin) produced
In response to GH, cells of the liver and skeletal muscle produce and secrete IGF (somatomedin)
How is growth hormone metabolically controlled
- Decrease in glucose or fatty acids leads to increase in GH secretion
- Increase in glucose or free fatty acid leads to decrease in GH secretion
- Give oral glucose tolerance test and see if GH becomes depressed to test GH function
- Fasting increase GH secretion, obesity decrease GH secretion
How is growth hormone controlled by CNS
- CNS regulates GH secretion via inputs into the hypothalamus effecting GHRH and somatostatin levels
- Surge in GH secretion after onset of deep sleep (good sleep)
Rapid eye movement sleep (light sleep) decreases GH secretion - Stress (trauma, surgery, fever) increase GH secretion
- Exercise promote GH secretion
- Surge in GH secretion after onset of deep sleep (good sleep)
Explain how feedback loops control growth hormone levels
- Long loop negative feedback mediated by IGF
- Inhibit release of GHRH from hypothalamus
- Stimulates the release of somatostatin from hypothalamus
- Inhibit release of GH from anterior pituitary
- Short loop negative feedback mediated by GH itself via stimulation of somatostatin release
What are the effects on cells of growth hormone
- GH stimulates long bone growth - both length and width increases prior to epiphyseal closure
- Only increase width after epiphyseal closure
- In response to GH, cells of the liver and skeletal muscle produce and secrete IGF (somatomedin)
- IGF stimulate both bone and cartilage growth
- In adults, growth hormone and IGFs help maintain muscle and bone mass and promote healing and tissue repair as well as modulating metabolism and body composition
What happens when growth factor binds to its receptor
- GH receptors activate Janus kinases (JAK) - tyrosine kinase receptor
- When growth factor binds to its receptor, cross phosphorylation of JAK occur
- Then phosphorylation of GH receptor and activation of signalling pathway
- Transcription factor activation and IGF production
Differentiate between two types of IGF
- IGF1 - major growth factor in adults
- IGF2 - mainly involved in fetal growth
What are the effects of IGF
- IGF act through IGF receptors to:
- Modulate hypertrophy- Modulate hyperplasia
- Increase in rate of protein synthesis]
- Increase in rate of lipolysis in adipose tissue
- Decrease in glucose uptake
What symptoms do pituitary tumours have
- Visual loss, headache, vomiting, nausea
- If tumour grows superior, it pushes and creates pressure against optic chiasm (chiasmal legion)
- Bitemporal hemianopsia - vision missing in the outer half of visual field
- Lateral growth of tumour can cause pain and double vision
- Ptosis (droopy eye) - causes eye compressive problems
What effect does pituitary tumour have on pituitary gland
- A tumour blocking portal system decreases production of pituitary hormones (hypopituitarism)
- Leads to increase in prolactin but decrease in other 5 hormones
How would you investigate pituitary tumour
- Identify anatomy, size and location of pituitary mass through MRI
- Assessment of visual field - bitemporal hemianopsia
- Assessment of endocrine function - hormone level in blood
What are the causes of effects of hypopituitarism
- Most commonly due to pituitary adenoma
- Sometimes due to radiation therapy, inflammatory disease, head injury
- Usually secondary to mass effect from adenoma
- Progressive loss of anterior pituitary function with GH and LH/FSH first hormones to be affected
- Deficiency in all tumours - panhypopituitarism
What are the effects of growth hormone deficiency
- Short stature in children, delayed or no sexual development
- May be due to gene mutation or autoimmune inflammation
- Adults - decrease tolerance to exercise, decrease muscle strength, increase body fat
- Usually due to mass effects from pituitary adenoma
- First hormone to become deficient
What are the effects of gonadotropin deficiency
- Delayed puberty in child
- Loss of secondary sexual characteristics in adults
- Loss of periods and early sign in women
What are the effects of TSH/ACTH deficiency
- Late feature of pituitary tumours
- TSH deficiency - symptoms of hypothyroidism
- ACTH deficiency - low cortisol levels, dizzy, low BP, low Na
What are the effects of ADH deficiency
- Excess excretion of dilute urine resulting in dehydration and polydipsea (increased sensation of thirst)
- Represents cranial form of diabetes insipidus
- Very high sodium levels (hypernatraemia)
- Reduced consciousness, coma and death
What are symptoms of hyperprolactinaemia
- Menstrual disturbance
- Fertility problems
- Galactorrhoea (milk secreted when not pregnant), erectile dysfunction
- Hypogonadism (diminished activity of gonads)
- Gynectomastia (hard breast tissue)
What are the causes of hyperprolactinaemia
- Most commonly due to prolactinoma - pituitary adenoma that secretes prolactin
- Could also be pregnancy, suckling, stress, exercise, drugs
What is the treatment of prolactinoma
- Dopamine agonist taken to shrink prolactinoma - no operation needed
- Dopamine inhibits prolactin
- Eg. Cabergoline
What are the symptoms of growth hormone excess
- Changes in physical appearance - broad nose, coarse facial features, thick lips, prominent supraorbital ridge (crest of bone on frontal bone of skull)
- Acromegaly
- Large extremities - large hands and feet
- Gigantism
- Growth factor secreting tumour
- Premature cardiovascular death, tumours, thyroid cancer, disfiguring body symptoms, hypertension
What is the treatment for acromegaly
- Surgical removal of tumour
- Radiation therapy - shrink tumour
- Drug therapy - dopamine receptor agonists to reduce GH secretion
- Synthetic somatostatin analogs to prolong suppression of GH secretion
What does ACTH excess cause
Cushing’s disease
