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Endocrinology Peripheral Endocrine Glands, Iodide Recycled, No Goiter,…
Endocrinology Peripheral Endocrine Glands
Thyroid Gland
Major cells that secrete thyroid hormone are organized into
colloid-filled follicles
Interspersed in the interstitial spaces between follicles are
C cells, which secrete calcitonin
Decreases blood calcium levels
Antagonist to the parathyroid hormone
Thyroid hormone is synthesized and stored on the
thyroglobulin molecule
Most steps of
thyroid hormone synthesis
take place on the thyroglobulin molecules within the colloid
Thyroid Hormone
Thyroid stimulating hormone (TSH) stimulates thyroid to secrete thyroid hormones, T4 (thyroxine) and T3 (triiodothyronine)
Thyroid hormones activate genes involved in
glycolysis
and
ATP production
Results in
calorigenic
effect
Increased
energy consumption and heat generation of cells
Responsible for strong, immediate, and short-lived increase in rate of cellular metabolism
Synthesis of Thyroid Hormone
Tyrosine-containing
Tg
produced within the thyroid follicular cells by the endoplasmic reticulum–Golgi complex is transported by exocytosis into the colloid.
Iodide
is carried by secondary active transport from the blood into the colloid by
symporters
(along with Na+) in the basolateral membrane of the follicular cells.
In the follicular cell, the
iodide is oxidized to active form by TPO
(Thyroid peroxidase, an enzyme) at the luminal membrane
The active iodide exits the cell through a
luminal channel to enter the colloid
.
Catalyzed by TPO, attachment of one iodide to tyrosine within the Tg molecule yields
MIT
, or
Monoiodotyrosine
.
Coupling of one MIT and one DIT yields
T3 (tri-iodothyronine)
1 more item...
Attachment of two iodides to tyrosine yields
DIT
, or
Di-iodotyrosine
Coupling of two DITs yields
T4 (thyroxine)
Effects
Increases the basal metabolic rate and exerts other effects
Effect on metabolic rate and heat production
Calorigenic Effect
Sympathomimetic effect
Sympathetic response
Effect on the cardiovascular system
Effect on growth and the nervous system
Secretion of growth hormone
More thyroid hormone = higher metabolicc rate (hyperthyroid)
Lesser thyroid hormone = lower metabolic rate (hypothyroid)
Physiological Functions
The general effect of thyroid hormone is to activate nuclear transcription of many genes.
Therefore, in virtually all cells of the body, great numbers of protein enzymes, structural proteins, transport proteins, and other substances are synthesized.
The net result is a generalized increase in functional activity throughout the body.
T3 and T4 enters cell membrane
T4 deiodinase to T3
T3 binds to hormone receptor
Nuclear transcription
Synthesis of new cells
Regulation
Increased thyroid hormone in the body fluids decreases TSH secretion by the anterior pituitary
Almost all this feedback depressant effect occurs even when the anterior pituitary has been separated from the hypothalamus
Body cannot always have high metabolism
Increased T3 and T4 sends negative feedback
Anterior Pituitary Gland reduces the secretion of
Thyroid Stimulating Hormone (TSH)
Hypothalamus reduces secretion of
Thyrotropin-releasing hormone (TRH)
Dysfunctions
Hyperthyroidism
Abnormal presence of thyroid-stimulating immunoglobulin (TSI) (Graves’ disease)
↑ T3 and T4, ↓ TSH
TSI is similar to TSH, so abnormal increase leads to goiter
Secondary to excess hypothalamic or anterior pituitary secretion
↑ T3 and T4, ↑ TRH and/or ↑ TSH
Increase in TSH lead to goiter
Hypersecreting thyroid tumor
↑ T3 and T4, ↓ TSH
T3 and T4 are increased because of tumour, not TSH stimulation. Hence no goiter
Hypothyroidism
Primary failure of the thyroid gland
↓ T3 and T4, ↑ TSH
Not enough T3 and T4 secreted by thyroid gland, so feedback sent to anterior pituitary gland to secrete more TSH.
Increase in TSH lead to goiter.
Secondary to hypothalamic or anterior pituitary failure
↓ T3 and T4, ↓ TRH and/or ↓ TSH
Hypothalamus or pituitary gland secrete insufficient TRH or TSH
Lack of dietary iodine
↓ T3 and T4, ↑ TSH
Lack of iodine means that T3 and T4 is produced insufficiently. Feedback sent to pituitary gland to secrete more TSH.
Increase in TSH lead to goiter
Adrenal Glands
Located on top of kidneys
Each adrenal gland consists of a
steroid-secreting cortex
and a
Catecholamine-secreting medulla
Adrenal cortex
Zona Glomerulosa layer
Mineralocorticoids (aldosterone)
The major effects of mineralocorticoids (Aldosterone) are on Na+ (retention) and K+ (elimination) balance
and blood pressure homeostasis.
Zona Fasciculata
Glucocorticoids (cortisol)
Sex hormones
(dehydroepiandrosterone)
Cortisol
Exert metabolic effects and play a key role in adaptation to stress
Inhibits CRH in hypothalamus
Inhibits ACTH in Anterior Pituitary Gland
Secretion
Peak cortisol concentration in body happens in the hour after awakening
Levels go down towards the night to prepare for sleep
Stressful events raise cortisol levels
Regulation
Sufficient levels of cortisol inhibits production of
CRH in Hypothalamus
CRF
ACTH in Anterior Pituitary Gland
Effects
Essentially increases metabolic fuel for the body's higher energy needs because of stress
Gluconeogenesis
Generation of glucose from certain non-carbohydrate carbon substrates
Protein mobilisation
Fat mobilisation
Stabilises lysosomes
More on sex hormones in sex reproduction lectures
Zona Reticularis
The adrenal cortex may secrete too much or too little of any of its hormones
Aldosterone hypersecretion
E.g. Conn's Syndrome, high retention of sodium, high secretion of potassium.
Cortisol hypersecretion
E.g. Cushing's Syndrome, exposed to high levels or cortisol for a long time.
Adrenal androgen hypersecretion
E.g. Polycystic ovary syndrome
Adrenocortical insufficiency
E.g. Addison’s disease mentioned in the tutorials. Hypoglycemia, diarrhoea, weight loss, fatigue
Catecholamine-secreting medulla
Adrenaline and noradrenaline
Sympathetic division of the Central Nervous System
The adrenal medulla consists of modified s
ympathetic postganglionic neurons
Adrenalinene (Epinephrine) and Noradrenaline (norepinephrine) vary in their affinities for different
receptor types
(alpha, beta)
Both are released in flight or fight response
Adrenaline reinforces the sympathetic nervous system and exerts metabolic effects
Adrenaline is released only on sympathetic stimulation of the adrenal medulla
Stress Response with Hypothalamus
See Diagram 19-13 of Sherwood
Endocrine Pancreas and Control of Fuel Metabolism
Exocrine
Not covered
Endocrine
Hormones secreted through the Islets of Langerhans
Beta Cells
Insulin
Insulin
Composed of two amino acid chains.
Connected to each other by disulfide linkages.
When the two amino acid chains are split apart, insulin’s functional activity is lost
When produced, it is in inactive form (proinsulin), C Chain connected to B and A Chains.
When activated, the C Chain is removed, and you get the mature or active form
Important as glucose levels in body needs to be controlled
Blood Glucose and Insulin Secretion
Food Intake
↑ Blood Glucose
Activate Beta Cells
Secrete Insulin
1 more item...
Suppresses alpha cells
Decreases production of glucagon
↑ Gastrointestinal Hormones
Parasympathetic Stimulation
Sympathetic stimulation inhibits the activation of beta cells. In this case, there will be glycogenolysis.
Deficiency
Blood glucose increase
Free fatty acids increases.
Leads to diabetic ketoacidosis, increase in acetoacetic acid.
Lack of glucose in cell, hence cell relies of its reserves to drive metabolism.
Leads to metabolic toxicity.
Problems
Hyperglycemia
Abnormally high glucose levels in the blood
Diabetes mellitus
Characterized by high glucose concentrations that overwhelm reabsorption capabilities of kidneys
Glucose appears in urine
Polyuria
Urine volume becomes excessive
Type I
Not producing enough insulin
Type II
Has insulin, but not working to bring glucose into cell
Hypoglycemia and Glucagon
Insulin excess causes brain-starving hypoglycemia (as less blood glucose is available for the brain).
Glucagon in general opposes the actions of insulin. Prevents blood glucose from going too low.
Glucagon secretion is increased during the postabsorptive state
Alpha cell activated, Glucagon secreted
Insulin and glucagon work as a team to maintain blood glucose and fatty acid levels
Alpha Cells
Glucagon
D Cells
Somatostatin
Pancreatic Polypeptide Cells
Pancreatic Polypeptide
Parathyroid Glands and Control of Calcium Metabolism
Intestinal Absorption and Fecal Excretion of Calcium and Phosphate
Embedded in the posterior surface of thyroid gland
Plasma Ca2+ must be closely regulated to prevent changes in neuromuscular excitability
Control of Ca2+ metabolism includes regulation of both Ca2+ homeostasis and Ca2+ balance
Parathyroid hormone raises free plasma Ca2+, a life-saving effect
Calcitonin decreases blood calcium, hence an antagonist to parathyroid hormone
Bone Remodelling
Bone continuously undergoes remodeling
Bone is continually being deposited by
osteoblasts
, and it is continually being resorbed where
osteoclasts
are active
Osteoblasts absorb the calcium released by osteoclasts
Osteocyte
is a bone cell formed when osteoblast becomes embedded in the material it has secreted
Canaliculi connects Osteoblast and Osteocyte
Facilitates transfer of Ca2+ via ATP pump or direct from bone to plasma
PTH and Ca2+
Mechanical stress favors bone deposition
PTH raises plasma Ca2+
PTH’s immediate effect is to promote transfer of Ca2+ from bone fluid into plasma
PTH’s chronic effect is to promote localized dissolution of bone in order to release Ca2+ into plasma
PTH acts on the kidneys, as it blocks the reabsorption of phosphate.
Vitamin D
Activation of vitamin D3 to form 1,25- dihydroxycholecalciferol.
Vitamin D is a hormone that increases Ca2+ absorption in the intestine
Vitamin D3 activated by liver and then by kidney to from 1,25- dihydroxycholecalciferol.
1,25- dihydroxycholecalciferol goes into intestinal epithelium, aiding the intestinal absorption of calcium
When there is too much calcium, 1,25- dihydroxycholecalciferol is reduced to almost zero.
Phosphate metabolism is controlled by the same mechanisms that regulate Ca2+ metabolism
As calcium increases, phosphate decreases
Disorders
Disorders in Ca2+ metabolism may arise from abnormal levels of PTH or vitamin D
PTH hypersecretion: excess PTH secretion
PTH hyposecretion: deficient PTH secretion (i.e., hypoparathyroidism, tetany)
Vitamin D deficiency: major consequence is impaired intestinal absorption of Ca2
May lead to rickets or osteomalacia (inadequate mineralisation of bones)
Balance of calcium in plasma, refer to page 38 of slides
Iodide Recycled
No Goiter
Layers outside in