ENI - Endocrine glands in detail Flashcards
Describe the location of the hypothalamus
- Diencephalon
- Below thalamus
- Floor of third ventricle
Outline the embryology of the anterior pituitary and intermediate lobe
- Evagination of oral ectodermal cells
- Rathke’s pouch
- True endocrine organ
Outline the embryology of the posterior pituitary
- Neural crest cells neuroectoderm
- Downward evagination of third ventricle
- Part of nervous system (storage function)
Which nuclei of the hypothalamus are linked to the posterior pituitary gland?
- Supraoptic
- Paraventricular
What is produced by the paraventricular nucleus in the hypothalamus?
- Oxytocin
- ADH
- TRH
- CRH
What is produced by the supraoptic nucleus in the hypothalamus?
Oxytocin and ADH
What is the function of the suprachiasmatic nucleus in the hypothalamus?
Biological clock/circadian rhythm
What is the function of the lateral nucleus of the hypothalamus?
- Arousal
- Hunger
What is the function of the arcuate nucleus of the hypothalamus?
- Energy status
- GnRH
- GHRH
- NP-Y
What is the function of the mammillary nucleus of the hypothalamus?
Wakefulness
What are the 3 types of input into the hypothalamus?
- Direct sensing by receptors
- Indirect humoural sensing (via blood) by receptors for circulating hormones
- Indirect neural sensing (via nerves) by visceral and somatic sensory nerves, limbic system (emotions) and reticular activating system
Give examples of direct sensing by the hypothalamus
- Thermoreceptors
- Osmoreceptors
Describe the role of the hypothalamus in thermoregulation
- Neurons in anterior hypothalamus respond to heat, initiate cooling centre, respond with peripheral vasodilation adn sweating
- Neurons in posterior hypothalamus respond to cold, initiate heating centre, respond with peripheral vasoconstriction, piloerection and shivering
Describe the role of the hypothalamus in osmoregulation
- Respond to increase blood osmolarity
- If dehydrated release ADH from SON, secreted via post. pit
- Kidneys retain water
- Stimualte neurons in thirst centre of lateral hypothalamus to find something to drink
Describe the role of the hypothalamus in energy balance
- Neurons in arcuate nucleus
- Sense blood glucose and hormones
- Leptin causes anorexigenic
- Ghrelin orexigenic
- Satiety centre responds to elevated glucose and inhibits eating
- Appetite centre responds to low glucose and stimulates eating
What are the outputs of the hypothalamus?
- Neurosecretory output to the posterior pituitary
- Inhibitory and stimulatory hormones to the anterior pituitary
Describe the neurosecretory output of the hypothalamus
- To posterior pituitary
- ADH and oxytocin
- Cell bodies in nuclei of hypothalamus
- Axons descend into posterior pituitary
- Nerves terminate on blood vessels and release hormone directly into circulation
- Simulates release of hypothalamic hormones ADH adn oxytocin stored in post pit into general circulation
Describe the inhibitory and stimualtory hormone output from the hypothalamus
- To anterior pituitary
- Secreted into blood
- Blood circulates from hypothalamus to anterior pituitary gland via pituitary portal circulation
- Control release of other hormones from anterior pituitary
Compare tonic and episodic secretion from hypothalamus
- Normal vs emergency
- Tonic: constant, some fluctuations e.g. CRH
- Episodic: when corrective response required, large release of hormone e.g. ADH, oxytocin
Give an example of how neuroendocrine hormones can act as hormones and neurotransmitters
- Dopamine
- Catecholamine that acts at heart via adrenergic receptors to stimulate heart and blood vessles
- Also inhibitory hypothalamic hormone
Define ultradian rhythm
Occuring more frequently than every 24 hours
Define infradian rhythm
At intervals longer than 24 hours
Define circadian rhythm
Biological process with 24 hour endogenous rhythmicity matching the rotation of the earth
Describe the biological clock of the hypothalamus
- Light sensed by retina
- Transmitted via nerve pathways to hypothalamus
- To suprachiasmatic nucleus
- Stimulation of pineal gland to produce melatonin
How are the hypothalamus and anterior pituitary connected?
Hypothalamic pituitary portal system
How are the hypothalamus and the posterior pituitary connected?
- Axons from SON and PVN of hypothalamus to posterior pituitary
- Release hormones into circulation
- Posterior pituitary is storage site
Describe the hypothalamic pituitary portal system
- Hypothalamic neurons terminate on primary plexus capillaries within hypothalamus
- Hypophyseal portal veins connect hypothalamus to anterior pituitary
- Secondary plexus within anterior pituitary
List the hypothalamic releasing hormones
- CRH (corticotropin-releasing hormone)
- TRH (thyrotropin-releasing hormone)
- GHRH (growth hormone/somatotropinn releasing hormone)
- GnRH (gonadotrophin releasing hormone)
- PRL-RH (prolactin releasing hormone)
List the inhibitory hormones of the hypothalamus
- GHIH/somatostatin (growth hormone inhibitory hormone)
- GnIH (gonadotrophin inhibitory hormone)
- Dopamine
What is the function of dopamine?
Inhibits prolactin and other hormones
Desribe the tonic inhibition of prolactin
- Held in inhibited state until release needed
- Inhibition maintained by dopamine
- PVN of hypothalamus
- Remains inhibited until stimulated by TRH, GnRH, PRL-RH, and nervous stimualtion from nursing/suckling
Describe the process of dopamine repression of PRL (prolactin)
- Dopamin secreted by PVN, travels in plexus
- Binds to G-protein coupled receptor on pit. cell
- Binding induces DAG/Ca2+, PKA intracellular signalling
- Switches off prolactin gene and blocks secretion of prolactin already in cell
- Blocks PRL production at every event within cell
Name the cell types found in the pars distalis of the anterior pituitary
- Thyrotropes
- Corticotropes
- Gonadotropes
- Somatotropes
- Lactotropes
Name the cell type found in the pars intemedia
Melanotropes
What is produced by the thyrotropes and where does it exert its action?
TSH, targets thyroid
What is produced by the corticotropes and where does it exert its action?
ACTH, targets adrenal cortex
What is produced by the gonadotropes and where does it exert its action?
FSH and LH, target gonads
What is produced by the somatotropes and where does it exert its action?
GH, targets liver, tissues etc
What is produced by the lactotropes and where does it exert its action?
Prolactin, targets mammary glands
What is produced by the melanotropes?
MSH (melanocyte stimulating hormone)
Describe the anterior pituitary cell types that can be defined by staining
- Chromophobes: stain poorly
- Chromophils: stain well and can be split into acidophils and basophils
- Acidophis: take up acid dyes (eosin, red)
- Basophils: take up basic dyes (haematoxylin, blue)
What anterior pituitary cells are acidophils?
- Somatotropes (GH)
- Lactotropes (PRL) (only when PRL in cytoplasm)
What anterior pituitary cells are basophils?
- Corticotropes (ACTH)
- Thyrotropes (TSH)
- Gonadotropes (FSH and LH)
Give the prevalence of each cell type in the pars distalis of the anterior pituitary
- Somatotrope 50%
- Lactotrope 15-20%
- Corticotrope 15-20%
- Gonadotrope 15-20%
- Thyrotrope 5%
What hormones regulate GH secretion?
- GH-releasing hormone (GHRH)
- Somatostatin (GHIH)
- Ghrelin
Describe the products of the corticotropes
- Produce prohomeone proopiomelanocortin (POMC)
- Cleaved to produce ACTH, MSH, beta-lipotrophic hormone, beta-endorphin, enkephalin and corticotropin-like intermediate lobe peptide (CLIP)
Describe the cleavage of POMC
- First POMC cleaved to ACTH using prohormone convertase-1
- Only in pars distalis and pars intermedia
- Then ACTH cleaved using prohormone convertase 2 in pars intermedia to give alpha-MSH and CLIP
What are the actions of growth hormone?
- Stimulates IGF-1 secretion from liver
- Stimulates protein synthesis
- Stimulates lipolysis
- Inhibits glucose utilisation by inhibiting insulin
Describe lactotrope regulation
- Tonic inhibition by dopamine
- Stimulated by TRH
- Hypertropy during pregnancy in preparation for lactation
- Placenta will signal back to mother to prepare for birth
Describe corticotrope regulation
- Stimulated by corticotropin releasing hormone (CRH)
- Negative feedback from ACTH
Describe thyrotrope stimulation
- Tonic stimulation
- TRH from hypothalamus
Describe the concept of negative feedback
- Something that is produced goes back up stream to turn off or reduce production of the negative feeback signal
- Closed, short and long feedback loops
Describe closed feedback loops
Target cells secrete hormones that affect their own secretion
- Usually negative
Describe open loops
- No direct feedback
- Stopped by removal of stimulus or depletion of biochemicals
- e.g. stimulation of milk let down
Describe short feedback loops (give an example)
- Feedback to the stimulating organ directly “above”
- e.g. ACTH from pituitary back to hypothalamus to reduce secretion of CRH
Describe long feedback loops (give an example)
- Feedback to further up the chain
- i.e. hormone from ultimate effector gland to initial stimulating gland
- e.g. cortisol from adrenal to hypothalamus to reduce secretion of CRH to reduce ACTH
Describe positive feedback loops
- Rare
- Secretion of hormone increases in response to feedback from that organ
- Amplification
- E.g. oxytocin in parturtition
What is meant by independent systems? Give examples
- Systems that do not depend on hypothalamus or pituitary gland
- Glucose regulation (insulin, glucagon, epinephrine)
- Calcium regulation PTH, calcitonin, active vit D)
- Sodium and potassium regulation
- Gastrointestinal enzyme secretion
Give examples of pituitary disorders
- PPID in horses
- Pituitary neoplasms
- Giantism
- Acromegaly
- Pituitary dwarfism
- Deletion of POMC gene in some labradors
What are the potential causes of hormone deficiency?
- Less functional tissue to produce hormone
- Interference with hormone synthesis such as dietary deficiencies
- Reduced stimulation from higher pathways
Outline pituitary dwarfism
- Most common in GS
- Cysts instead of adenohypophysis
- No GH = small dog
- No ACTH = hypoadrenocorticism
- No TSH = hypothyroidism
- Small, abnormal coat, metabolism non-functional
- Most die stillborn, some live up to 5 years
- In utero exploit maternal hormones
What may cause hormone excess?
- Increased synthesis of hormone by affected tissue
- Loss of negative feedback control due to:
- Hormone was never under -ve feedback control
- Tissue continues secretion regardless of stimulating hormone
- Unable to send signal, or upstream tissue unable to receive/respond to signal
Outline adenomas of pars distalis
- Overproduction of ACTH and GH
- Non-function
Outline GH-secreting pars distalis tumours
- Affects acidophils within pars distalis
- very rare
- Excess GH and IGF-1 from liver
- Alters growth, and affects energy metabolism
- Differential diagnosis for diabetes mellitus
Outline giantism
- Hyperactivity or neoplasia before adolescence
- All tissues grow rapidly incl bones
- Hyperglycaemia as GH antagonises insulin
- Pancreatic failure due to overwork
- Diabetes mellitus
- Eventually pan-hypopituitarism due to negative feedback loop
Outline acromegaly
- Pituitary disorders after adolescence
- Epiphyses of bones fused
- Only bones of extremities grow (paws)
- Membranous bones of face grow
- Mandible continue to grow leading to prognathism
- Eventual organ enlargement
- Kyphosis of vertebrae (hunchback)
What is the function of ADH?
Acts on renal tubules to retain water
Outline the detection of dehydration by osmoreceptors
- Within hypothalamus
- Respond to an increase in osmolarity of ECF
- More ADH released
- More water conserved and behaviour to find a drink
OUtline the detection of dehydration by stretch receptors
- Volume receptors in atria and veins
- Respond to large changes (10%
decrease) - Decrease in distension detected
- nervous impulses to hypothalamus, more ADH released = water conservation
Outline the integration of signals from osmoreceptors in hypothalamus and stretch receptors
- Osmoreceptors most sensitive
- Stretch receptors triggered as emergency response where there is a large decrease in volume
Where does ADH act?
Distal tubule and colleccting duct
Where are aquaporins always present?
- In proximal ubule on all membranes
- In distal tubule and collecting duct always on baso-lateral membranes
Where are aquaporins inserted under the influence of ADH?
Apical membranes
Explain how ADH inreases aquaporin density on tubule surfaces
- ADH binds to receptors
- Activates adenyl cyclase
- Produce cAMP
- Vesicles containing AQP-2 move to cell surface
- Inserted via exoctysosi
- Proportional to plasma ADH concentration
What is diabetes insipidus?
Increased urine output caused by ADH dysregulation
What are the 2 types of diabetes insipidus?
- Neurogenic
- Nephrogenic
Describe neurogenic diabetes insipidus
- Inadequate ADH released from pituitary
- Must be this if injection of exogenous ADH leads to concentrated urine
Describe nephrogenic diabetes insipidus
- Inadequate response to ADH within the kidney
- Will not respond to exogenous ADH
What is congenital diaebtes insipidus caused by?
AQP-2 deficiency (nephrogenic)
Describe the role of prolactin in milk synthesis
- mRNA for milk protein synthesis
- alpha-lactalbumin (aLA) for lactose production
What is the role of lactose in milk?
- Draws water into gland
- Easily digestible so ideal for neonate
Describe the role of alpha-lactalbumin
- Lactose productioin
- Is a whey protein produced by mammary epithelial cells, forms complex with galactosyl transferase to form lactose synthase
What is the role of oxytocin?
- Stimulates milk let down
- Uterine muscle contraction duing parturitio
- Induces contraction of alveoli in mammary glands
Outline the neural transmission to stimulate oxytocin release
- High density of sensory nerve fibres in teats, detects suckling or prep for milking
- Impulses via superficial sensory pathways of spinal cord
- Afferent sensory neurons enter lumbar segments of spinal cord
- Ascend spinal cord sensory tracts
- To thalamus, influence cell bodies of neuroendocrine cells
- Stimulates secretion of oxytocin from nerve endings in posterior pituitary gland into circulation
Describe the action of oxytocin in the mammary glands
- Increases pressure within alveoli as myoepithelial cells surrounding alveoli contract
- Reduces resistance in excretory ducts as myoepithelial cells orientated along long axis of secretory duct, so when contract duct becomes shorter and wider, causing relaxation
- Reduces resistance in teat canal
- Results in increased milk outflow
Outline how oestrogen:progesterone ratio affecs oxytocin
- Progesterone blocks oxytocin recetpros
- Oestrogen increass oxytocin receptors
- In pregnancy, ratio is lower and so inhibits oxytocin
- In parturition is higher, stimulating oxytocin
Describe the neuroendocrine reflex at parturition
- Stimulation of sensory nerve endings in cervix
- Afferent nerve impulses to the hypothalamus
- Neuroendocrine cells of PVN and SON depolarise
- Secrete oxytocin from pars nervosa
- Enters blood circulation, acts on receptors of myometrium
- Atrong uterin contractions
Describe the clinical relevance of oxytocin
- Can be administered to induce parutrition in horses
- Other strategies to promote/mimic effect of oxytocin (oestrogen/oestradiol, dexamethasone, PGF2a)
- Treatment for uterine inertia
- Retained placenta
Describe the HPA axis
- Hypothalamic-pituitary adrenal axis
- Hypothalamus secretes CRH, acts on ant. pit to secrete ACTH, acts on adrenal cortex to secrete corticosteroids
- Long and short negative feedback loops
Describe the HPT axis
- Hypothalamic-pituitary thyroid axis
- Hypothalamus secretes TRH, ant pit secretes TSH
- Acts on thyroid gland to secrete T4 (thyroxine) and T3 (triiodothyronine)
Describe the male HPG axis
- Hypothalamic-pituitary gonadal axis
- Hypothalamus secrete GnRH, (GnIH)
- Ant. pit secretes FSH and LH if GnRH secreteed
- Stimulates testes to secrete inhibin (FSH stimulated) and testosterone (LH stimulated)
Describe the female HPG axis
- Hypothalamic pituitary gonadal axis
- Hypothalamus secretes GnRH (or GnIH if inhibiting)
- Ant. pit secretes FSH and LH
- In ovaries, FSH stimulates oestradiol and LH stimulates progesterone
Outline the control of melatonin release
- Pineal gland responds to light
- More melatonin when dark less when light
What are the actions of melatonin?
- Induces sleep
- Control of moulting
- Seasonal reproduction
Describe melanin production
- Melanocytes in skin
- Stimulated by MSH from melanocytes in pituitary gland (pars intemedia) and hypothalamic neurons (arcuat nucleus)
Outline the link between melatonin and MSH
- Seasonal haircoat colour changes
- Seasonal haircoat shedding (horses)
- Seaonal anoestrus (horse)
Describe the location of the adrenal glands
- On medial side of cranial pole of skidney
- Paired and asymmetrical
What are the zones of the adrenal cortex?
- Zona glomerulosa (most outer)
- Zona fasciculata (middle)
- Zona reticularis (most inner)
Describe the adrenal medulla
- 10-20% of gland
- Neuroendocrine tissue
- Secretes catecholamines
- Acts as post-ganglionic ganglion cells (sympathetic)
What is the embryological origin of the adrenal medulla?
Autonomic nervous system
