1. Describe the functional anatomy of the hypothalamic-pituitary unit
hypothalamus surrounds or lines the 3 ventricle of the brain immediately superior to the
pituitary. Connected to the pituitary by a narrow stalk of unmyelinated axons and network of
blood vessels. Neurohypophysis (posterior pituitary) and adenohypophysis (anterior
2. Name the types of hypothalamic neurons and their functions
Magnocellular neurons terminate in posterior pituitary and secrte vasopressin and oxytocin,
parvicellular secrete release/inhibiting hypophyseal factors into portal system such as TRH,
CRH, GHRH, GnRH, hypothalamic projection neuron synapses with neuronal targets.
3. Describe the terms circadian, diurnal, ultradian
Episodic secretion in rhythms that are: circadian is around 24 hours, diurnal is exactly 24
hours and ultradian is minutes of hours
4. Discuss the generation and importance of episodic endocrine secretion.
Secreted in bursts
5. Outline the 5 hypothalamic-anterior pituitary axes and 2 posterior pituitary axes
- ACTH is derived from POMC (also makes α-
MSH and B-endorphins)
- α-subunit is common to FSH and LH, heavily glycosylated
GH acts on TKAR (tyrosine kinase-associated
- generally anabolic - PRL release is controlled
by TRH (positive) and
dopamine and PIF
- Receptors are TKAR
- Usually under tonic
inhibition by dopamine
- Estradiol stimulates PRL
- Plays a major role in
maintenance of teticular
- common α subunit
- AVP and OXY are made with neurophysin (prevents axonal leackage) and GP/
Vasopressin – stimulated by osmoreceptors (oragnum vasculosum of the lateral terminalis),
baroreceptors and volume receptors. Renin-agiotensin system is also involved.
Oxytocin – released following mechanical stimulation to the nipple, stimulates contraction of
ductual myoepithelium. Also causes contraction of smooth muscle in response to vaginal
stimulation or cervical stretching. Possibly involved in feeding behaviour and satiety, gastric acid
secretion, BP, temp and HR, stimulation of glucagons secretion, stress responses, tubule
contraction and sperm transfer to testes.
6. Define the major endocrine disorders associated with the posterior pituitary Diabetes Insipidus – Hypothalamic or central DI is due to lack of vasopressin. Causes large
urine volume that is hypotonic and dilute and often accompanied by polydipsia (excessive thirst).
Can be caused by tumours, hereditary, granulomatous diseases, sarcoidosis.
SIADH – Syndrome of Inappropriate Anti-Diuretic Hromone Secretion. Decreased plasma
osmolality, inappropriate urine concentration (elevated Na+), euvolemic. May be caused by
tumours, CSN disorders, drug-induced, pulmonary disease.
1. Locate and describe the anatomy of the thyroid
- bilobed gland of endodermal origin, lies of the ventral surface of the trachea below the
cricoid cartilage. About 15-20 grams in humans.
2. Describe the role of thyroglobulin
- Thyroglobulin is high MY, heavily glycoslated, About 330 tyrosine residues which can
be iodinated to form thyroxine (T4) and triiodothyronin (T3).
3. Explain the mechanism and regulation of thyroid hormone formation and the role of
- Thyroid cells have sodium iodide symporter (NIS) (requires Na/K ATPase). Pendrin is
the apical iodide transporter.
- Thyroperoxidases oxidize the iodine and iodinate tyrosine residues on TG (1-2 added)
- TSH mostly stimulates iodide transport and TPO activity and Tg production
4. Discuss the factors regulating thyroid hormone levels (binding proteins, deiodinases,
- Since steroids, must bind transport protein. Thyroxine binding globulin (TBG)
transports 75% T3 and T4, high binding affinity. Transthyretin (TTR) transports 20%
of T4 and 5% T3. Human Serum Albumin transports 5% T4 and 20% T3. Low binding,
but lots available.
o Binding proteins regulate the bioavailability and half-life of T3/T4. Without,
would be rapidly cleared.
- T4 is converted to T3 by deiodinases
5. Explain the cellular mechanism of action of thyroid hormone
- Thyroid hormone receptors acts a transcriptional repressor (is a nuclear receptor) in a
complex with retinoid X receptor (RXR). At low levels, T3 releases co-repression, at
high levels, recruits co-activators.
6. Define the physiological role of thyroid hormones in development and the adult including
major effects on cellular metabolism.
- Required for the secretion and action of GH, essential for early neural development,
maternal T3/T4 can compensate. Lack of maternal T3/T4 can result in growth retardation
- In adults increases basal metabolic rate, mitochondrial growth, replication and activity.
Stimulates Na/K ATPase, increases transcription of metabolism enzymes, permissive to
action of GH, induces expression of GH, PRL, NGF, surfactant, generally increase
cellular metabolic activity.
7. Illustrate examples of thyroid pathology Edemic Goiter – lack of (-) feedback, no iodine available.
Hashimoto’s – autoimmune disorder where antibodies to the TPO enzyme are formed, inhibits
T3 and T4 production.
- Both are hypothyroidism and can result in slower HR, muscle cramping, feeling cold,
puffy eyelids, lack of concentration and poor memory, and lack of energy.
- Hyperthyroidism – feeling hot, increased sweating, fast HR, nervousness, trembling
Grave’s Disease – antibodies to TSH receptor
8. Name my least favourite hormone
Calcitonin – inhibits osteoclas activity, decreases Ca++ tubular reabsorption. Lowers Ca++
Insulin and Glucose Homeostasis
1. Compare and contrat metabolsi mduring the absorptive and post-absorptive states
Absorptive State: Net uptake of glucose, glycogenesis, net protein synthesis
Post-absorptive State: hepatic glycogenolysis, gluconeogenesis, lipolysis.
2. Define chylomicrons and VLDL
- chylomicrons are large lipoprotein particles that transport dietary proteins. They are
manufactured in epithelial cells in small intestine. Triglycerides, cholesterol, cholesterol,
esters, and apoproteins, transported via the lymphatic system.
- VLDL is a very low density lipoprotein, made by the liver. Broken down to free fatty
acids and glycerol by lipoprotein lipase in endothelial cells, re-assembled in adipose
3. Disucss the importance of the various subtypes of glucose transporters
GLUT1 – in the brain, erythrocytes, placenta, fetal tissue. Low Km, constant uptake of glucose
GLUT2 – liver, kidney, intestine, pancreatic B-cells. High Km, glucose equilibrium across
GLUT3 – brain. Medium Km, insulin-sensitive
GLUT4 – muscle and adipose. Med Km and also insulin-sensitive
GLUT5 – jejunum. Medium Km, fructose uptake.
4. Name the endocrine cells of the pancreas and their hormones
- Alpha-cells produce glucagons, beta-cells produce insulin and amyloid, delta-cells
produce somatostatin, D1 cells produce VIP, PP cells produce pancreatic polypeptide
5. Describe the mechanism of glucose regulation of insulin secretion
- First peak 1-5 min of glucose load, 2 peak occurs 15-20 min later.
6. Describe the cellular mechanism of action of insulin st
- Second longer phase of insulin secretion is largely dependent on the 1 phase. The rise in
intracellular Ca++ activates CaM kinase which activates transcription of the insulin gene.
Secreted insulin binds to B cell insulin receptors which increases transcription of the insulin gene
via the PI3kinase pathway.
Insulin receptor: has IgG domain, cystine-rich region, transmembrane domain, kinase domain,
protein interaction domain and c-term tail. Second messangers include STATs, PI3K, PLC,
MAPK. Uses IRS proteins. Signal Termination: receptor dephosphorylation, Ca++ pumps, ph