LECTURE 6 - central endocrine glands Flashcards
What is the pituitary gland and where is it found?
- master gland
- controls all other glands
- 2 parts; posterior and anterior
- sits below hypothalamus
What is the hypothalamus?
- collection of brain nuclei (or centres)
Important functions: - homeostasis and primitive functions
- controls autonomic function via brainstem autonomic centres
- controls endocrine function via pituitary gland
What does the hypothalamus respond to?
Environmental factors
e.g. light, stress, fear etc
Neural signals
e.g. visceral afferents from heart, liver, stomach
Hormones
Negative feedback
What are the properties of hypothalamic hormones?
- small peptides with short half lives (t1/2)
- release is pulsatile => rapid effects on the release of cognate anterior pituitary hormone
- can be used clinically in acute challenge experiments to check pituitary function
Describe the differentiation between the lobes of the pituitary glands
ANTERIOR
- hormones regulated by secreted hypothalamic factors
- controls circulation
- hormones released into blood supply
POSTERIOR
- synthesised in hypothalamus and transported via neuronal projections
- structurally continuous with the hypothalamus, remains attached by the hypophyseal (or pituitary stalk)
- gets info from nervous system
What are some anterior pituitary hormones?
Cell type - hormone - function
Thyrotroph - TSH - thyroid hormone regulation
Corticotroph - ACTH - regulation of adrenal cortex
Gonadotroph - LH/FSH - reproductive control
Somatotroph - GH - growth
Lactotroph - PRL - milk production
What are some posterior pituitary hormones?
Cell type - function
ADH (vasopressin) - water regulation
Neurophysins - important in ADH synthesis
Oxytocin - birth, breast milk expression
What are tropic hormones?
Hormones that target other endocrine glands
What is TSH?
Thyroid stimulating hormone
- aka thyrotropin or thyrotrophin
- made in thyrotrophs in response to pulsatile TRH release from hypothalamus
How can the pituitary gland regulate thyroid activity?
- hypothalamus receives signal
- produces TRH (thyroid releasing hormone) the reacts with ant. pituitary to produce TSH
What are some thyrotroph problems?
Pituitary failure
- primary hypothyroidism = problem with thyroid itself
- secondary hypothyroidism = problem due to fault elsewhere e.g. not enough TSH production
Pituitary tumour = secondary hyperthyroidism
What hormones are produced by the gonadotrophins?
LH and FSH
- made in anterior in response to GnRH
- 60% secrete both, 18% secrete only LH and 22% only FSH
Explain the effects and mechanism of action of LH and FSH
- regulate testosterone biosynthesis and spermatogenesis
- regulate the menstrual cycle and fertility in the ovary
- both act through cell membrane receptors coupled to G proteins => elevations in cAMP and activation of protein kinase A
- pulsatile secretion essential for actions
What is ACTH and how is it synthesised?
Adrenocorticotrophic hormone - aka adrenocorticotrophin
- polypeptide of 39 amino acids
Synthesis:
- large precursor Pro-opiomelanocortin (POMC) is the source of several important biologically active substances
- ACTH = cut from POMC
How is cortisol released in response to ACTH?
- stress = hypothalamus releases CRH (corticotrophin releasing hormone)
- interacts with receptor to cause release of ACTH
- interacts with receptor to cause cortisol release from adrenal cortex
What are the effects of ACTH?
- ACTH stimulates G-protein receptor coupled to cAMP
- this stimulates the enzyme that converts cholesterol to cortisol or sex steroid precursors
- ACTH rises with stress - this is used clinically to test corticotroph function following insulin challenge
How is prolactin regulated?
- made by increasing number of lactotrophs
- maintained by -ve feedback
- production of dopamine inhibits production of prolactin, but can be unregulated by TRH and VIP (vasoactive intestinal peptide)
- dopamine release from hypothalamus regulated by stress, sleep and suckling stimulus
What are the effects of prolactin?
- lymphocyte regulation
- osmoregulation
- steroid production
- stimulates mammary gland development
- maintains lactation
What are prolactinomas?
- tumour of pituitary gland (most common one)
- interferes with HPG axis resulting in infertility and other ailments
- treatment = dopamine agonist e.g. bromocriptine
Hypothyroidism can lead to hyperprolactinaemia due to elevations in TRH –> increased prolactin production
What are the properties of growth hormone?
- aka somatotropin
- released throughout life
- pulsatile release
- stimulated by low glucose, exercise and sleep
- effects mediated by GH and IGF1
What are the stimulatory factors regulating GH release?
- GHRH
- dopamine
- catecholamines
- excitatory amino acids
- thyroid hormone
What are the inhibitory factors regulating GH release?
- somatostatin
- IGF1
- glucose
- FFA
What can result from an excess or deficiency of GH?
Excess:
- excessive amounts of IGF1 => abnormal growth of tissue or skeleton
- -> acromegaly and gigantism
Deficiency or resistance:
- GH receptor mutations - Laron syndrome dwarfism - treated with IGF1
- GH deficiency - treated with recombinant hGH
What are the causes of hypopituitarism?
hypopituitarism = diminished hormone secretion
Causes:
- pituitary tumour
- brain surgery
- trauma (road accidents)
- blocked blood supply, bleeding, inflammation
- autoimmunity
- infection
What is arginine vasopressin?
AKA antidiuretic hormone (ADH)
- nonapeptide secreted from posterior pituitary
- synthesised and packaged with a carrier protein (neurophysin) in the secretary granules
- granules move down to the ends of the fibres
- both released upon stimulation of the nerves
How is ADH secreted?
- acts on collecting ducts of kidney
- CD intrinsically impermeable to water
- ADH stimulates production of water channels and their incorporation into the walls of the CD
- this allows reabsorption of free water from tubular fluid
- can convert a very dilute using to a concentrated one
(increase ADH to retain water)
What are the effects of an ADH excess or deficiency?
ADH excess
- caused by variety of conditions e.g. head trauma, secreting tumours
SIADH = syndrome of inappropriate ADH secretion
- hyper water retention leads to highly concentrated urine
- hypo water retention = excess water excretion
How does ADH link to diabetes insipidus?
- ADH controls serum osmolarity
- if posterior pituitary damaged, ADH may be reduced and urine cannot be concentrated
- Polyuria (XS urine production) and polydipsia (XS drinking) are a result of diabetes
- Hypernatraemia and increased serum osmolarity result
- diagnosed by having a dilute urine in the context of concentrated plasma
What does oxytocin do?
- stimulated contraction of smooth muscle of breast and uterus
- can be given to induce labour
- plays roles in milk ejection reflex and parturition (birth)
What aren neuro-endocrine reflexes?
- occurs when neuro-endocrine cells secrete hormones from the neural axon terminals into the blood in response to some neural signal
- e.g. oxytocin
