1
Q
Endocrine System
A
- Major regulatory system of the body
- Uses hormones to produce homeostatic adjustments
- Composed of glands (specialized cells, or organ that secrete substances to be used by or eliminated from the body)
2
Q
Functions of the Endocrine System
A
- Maintain constant internal environment via regulation of metabolism and H20/electrolyte balance
- Adaptive stress response
- Growth and development
- Reproduction
- Red blood cell production
- Integrated with ANS in regulating circulation and digestive functions
3
Q
Hormones
A
- Chemical substances secreted directly into the blood at low quantities
- Exert physiological effect at a distant target tissue
4
Q
Hydrophilic Hormones
A
- Water soluble and low lipid solubility
- Found unbound to carrier molecules in plasma
- Peptide hormones, amines (single amino acids)
Amine hormones:
- Catecholamines (Norepinephrine and epinephrine)
- Thyroid hormones (exception, are not hydrophilic)
5
Q
Peptide Hormones Synthesis
A
Synthesis:
- Large precursor proteins called preprohromones are synthesized by endoplasmic reticulum ribosomes
Packaging:
- Preprohormones are processed into active hormones and packaged into secretory vesicles through the ER and Golgi complex
Storage:
- Secretory vesicles stored until appropriate signal
Secretion:
- Signals initiates exocytosis of vesicles and hormones into the blood
6
Q
Lipophilic Hormones
A
- Highly soluble in lipids and poorly soluble in water
- Require carrier molecules for transport
Amine thyroid hormones
Steroid hormones
7
Q
Steroid Hormones Synthesis
A
- Synthesized from a single cholesterol molecule
- The hormone produced is dependent on the specific enzyme within the tissue’s cells
- Released a synthesized
- Regulate its synthesis
8
Q
Hormones Interacting with their Target Cells
A
Only freely, unbound hormones can interact with receptors at it’s target cell
- Therefore lipophilic hormones require carrier molecules
- Hormones are dynamically unbinding and rebinding to carrier proteins, resulting in a small fraction being unbound and active at a given time.
9
Q
Peptide and Catecholamines Affects after Receptor Binding
A
Surface receptor binding activates secondary messenger systems
- amplify initial signal, as low concentrations of hormones trigger response.
Cyclic AMP (cAMP):
- Messanger binds to receptor, activating G Protein
- G shuttles and activate adenylyl cyclase which converts ATP to cAMP
- cAMP activate protein kinase A which phosphorylates and activate target proteins
Calcium:
- Messanger binds to receptor, activating G Protein
- G shuttles and activate phospholipase C enzymes which converts PIP2 to IP3 and DAG
- IP3 mobilizes Ca2+ to activate proteins kinase which phosphorylate target proteins
10
Q
Steroid and Thyroid Hormones Affects after Receptor Binding
A
- These hormones are able to pass through plasma and nuclear membranes
- Bind to intercellular receptors
- Effects regulate gene transcription and protein synthesis
11
Q
Lipophilic Hormones and Protein Synthesis
A
- Free lipophilic hormone diffuse across membrane to interact with intracellular receptors.
- The hormone-receptor complex (H-R) binds to the hormone response element (HRE) within the DNA.
- DNA binding activates specific genes and produces messenger RNA (mRNA ).
- The mRNA leaves the nucleus.
- The mRNA binds to a ribosome and proteins are synthesized.
- These newly synthesized proteins ultimately lead to the cellular response of the hormone
12
Q
The Pituitary Gland
A
Small gland located in the bony cavity at the base of the skull
- Divided into two anatomically and functional distinct lobes
Posterior Pituitary Gland:
- Comprised of neural like tissue and sometimes call the neurohypophysis
Anterior Pituitary Gland:
- Comprised of glandular epithelial tissue and is call the adenohypophysis
13
Q
Relationship Between the Pituitary and Hypothalamus
A
The hypothalamus controls the hormone release from each pituitary lobe
Posterior Pituitary Lobe:
- Hypothalamus connected to lobe by neural pathways
- Hypothalamus contains two cluster of neurons called the supraoptic nucleus and paraventricular nucleus
- Axons project down pituitary stalk and terminate on blood vessels in the posterior pituitary
Anterior Pituitary Lobe:
- Hypothalamus connected by vascular link, hypothalamus-hypophyseal portal system
- Hypothalamus secrete hormones into this portal which inhibit or promote release of anterior pituitary hormones
14
Q
Hormones of the Posterior Pituitary Gland
A
Hormones synthesized in neuronal cell bodies located within the hypothalamus
- Packaged into vesicles which are transported down axons into the posterior pituitary
- Vesicles releases from neuronal signal
Vasopressin:
Antidiuretic hormone
1) enhancing the retention of water by the kidneys
2) causes contraction of arteriolar smooth muscle.
Oxytocin:
1) stimulating contraction of uterine smooth muscle cells during childbirth
2) promoting milk ejection during breastfeeding
15
Q
Hormones of the Anterior Pituitary Gland
A
Peptide hormones synthesized and secreted in anterior gland
Tropic Hormones: Once release they stimulate endocrine glands to release their hormones
- Growth Hormone (GH)
- Adrenocorticotropic Hormone (ACTH) - Stimulates secretion of cortisol by the adrenal cortex
- Luteinizing Hormone (LH) - Stimulates secretion of estrogen and progesterone from ovaries and testosterone from testicles
- Thyroid Stimulating Hormone (TSH)
- Follicle Stimulating Hormone (FSH) - Stimulates growth and development of ovarian follicles and estrogen secretions. Required for sperm production
- Prolactin (PRL) - Not Tropic. Enhances breast development and milk production
16
Q
Hypothalamic-Hypophyseal Portal System
A
- Hypophysiotropic hormones produced by neurosecretory neurons in hypothalamus enter the hypothalamic capillaries
- Capillaries rejoins to form the hypothalamic-hypophyseal portal system
- Portal system branches into the capillaries of the anterior pituitary
- Hypophysiotropic hormones control the release of anterior pituitary hormones
- Pituitary secrete hormones into capillary which rejoin into veins
17
Q
Regulation fo Anterior Pituitary Hormone Secretion
A
Hypothalamus releases inhibitor hormones into hypothalamic-hyopphyseal portal system
- Thyrotropin-Releasing Hormone (TRH) - stimulates release of TSH and Prolactin
- Gonadtropin-Release Hormone (GnRH) - Stimulate release of FSH and LH
- Growth Hormone Inhibiting Hormone (GHIH) - Inhibits release of GH and TSH
- Corticotropin - Release Hormone (CRH) - Simulates ACTH
- Growth Hormone Releasing Hormone (GHRH)
- Prolactin Releasing Hormone (PRH)
- Prolactin Inhibitory Hormone (PIH)
18
Q
Control of Hypothalamic Releasing and Inhibiting Hormones
A
Controlled by neuronal and hormonal inhibitory and stimulatory inputs
- Some parts of the hypothalamus don’t have blood brain barrier so can monitor concentrations in the blood
19
Q
General Chain of Endocrine Commands
A
- Hypothalamic hormones released into hypothalamic-hypophyseal portal system to regulate posterior gland
- Tropic hormones released into capillaries to target endocrine gland
- Third hormone released from endocrine gland to produce physiological effect vat target cell
20
Q
The Thyroid Gland
A
Located over the trachea just below the larynx
- Two lobes connected by inner section called the isthmus
- Lobes have same function
21
Q
Thyroid Hormones
A
Two hormones produced from AA tyrosine
- Contain iodine
- Have the same function, with T3 having higher speed and intensity of action
- T4 converted to T3 in target tissues
Tetraiodothyronine:
- 90% of thyroid hormones secreted
Triiodothyronine:
- 10% of secreted hormone
22
Q
Importance of Iodine
A
The body requires about 1mg of iodine a week to ensure sufficient levels of thyroid hormone
- Thyroid gland extracts essential all iodine from the blood and stores it
23
Q
Synthesis of Thyroid Hormones
A
- Tyrosine-containing thyroglobulin is produced within the follicular cells by the ER-Golgi complex and is transported to the colloid by exocytosis.
- Iodide is taken up by follicular cells through iodide trapping. Iodide is driven
against its concentration gradient by using a Na+-cotransporter that moves down its gradient. - Iodide is then transferred into the colloid of the follicular lumen.
- Iodide moves into the colloid. thyroperoxidase converts iodide into a highly reactive state which immediately attaches to a tyrosine residue on a thyroglobulin molecule. This process is called iodide organification. This produces monoiodotyrosine (MIT) and diiodotyrosine (DIT).
- A coupling process occurs that combines MITs and DITs to form the thyroid hormones.
24
Q
Release of Thyroid Hormones
A
- The follicular cells engulf thyroglobulin-containing colloid by phagocytosis and create hormone-filled vesicles.
- Lysosomes fuse with the vesicles and digestive enzymes releaseall of the MIT, DIT, T3, and T4 from the thyroglobulin.
- Because T3 and T4 are very lipophilic they immediately cross the plasma membrane to the blood where they bind to plasma proteins, mainly thyroid-binding globulin
25
The Actions of Thyroid Hormones
- Effect most tissues of the body
- Slow to action and duration can last for days until hormone plasma concentration decreases.
1. Metabolic Rate and Heat Production - increase oxygen consumption energy and expenditure
2. Intermediary Metabolism - Conversion of glucose and glycogen (low hormone concentration converts glucose the glycogen and vice versa)
3. Sympathomimetric - In response to catecholamines by increase number of receptors
4. Cardiovascular System - Sympathemimetric actions can increase heart rate and contraction strength
5. Growth -
25
Hypothalamic Pituitary Thyroid Axis
1. Hypothalamus release Thyrotropin Releasing Hormones (TRH) to stimulate anterior pituitary gland
2. Release of Thyroid Stimulating Hormone (TRH)
3. Absence of TSH causes thyroid gland to shrink, while excess causes follicles to expand
- TSH and TRH are under negative feedback control
26
Hypothyroidism
Underactive thyroid does not secrete enough thyroid hormones
Primary Failure:
- Hashimoto thyroiditis, is an autoimmunde disorder in which antibodies target thyroid and impair T3 and T4 production. Elevated levels of TSH seen.
Secondary Failure:
- Hypothalamus/pituitary fail to secrete adequate TRH or TSH
Inadequate Dietary Supply of Iodine:
- Most common cause of hypothyroidism
- Low production of T3 and T4
27
Symptoms of Hypothyroidism
- Cold Intolerance
- Slower Reflexes
- Reduced mental alertness
- Easy to fatigue
- Slow/weak heart rate
- Weight gain
Congenital hypothyroidism (acquired at birth) cretinism - leads to dwarfism and intellectual disability
28
Hyperthryoidism
Excess Hypothalamic or Anterior Pituitary Secretions:
- Tumours cause excess TRH and TSH secretion, causing elevated T3 and T4
Thyroid Tumour:
- Causes increase Secretion of thyroid hormones
Graves Disease:
- Autoimmune disease which produces long-acting thyroid stimulator, which activates TSH receptors
29
Goiter
- Symptom that can arise from hyper and hypothyroidism
- Enlarged thyroid gland
- From increased TSH which stimulates thyroid gland to increase numbers and size of follicles
30
Adrenal Glands
- Small and located on top of kidneys
- Cortex composes the outer layers of glands and secrete steroid hormones
- Inner layer is the medulla, which secretes catecholamines
31
The Adrenal Cortex
Three distinct zones:
- Zona glomerulosa
- Zona fascisulata
- Zona reticularis
- Produce steroid hormones with cholesterol as the precursor molecule
- Each layer has different enzymes allowing for varying hormone production
32
Categories of Adrenal Cortex Hormones
Mineralocorticoids:
- Influence mineral (electrolyte) balance
- Produces in the zona glomerulosa
Glucocorticoids:
- Role in glucose, lipid and protein metabolism
- Produced in the zona fasciculata and reticularis
Sex Hormones:
- Identical to those producd in gonads
- Low quantities produced in zona fasciculata and reticularis
33
Mineralocorticoids
- Class of corticosteroids produced in the adrenal cortex
- Influence salt and water balances
- Without mineralocorticoids, a person would die in a few days from circulatory shock (low blood pressure)
- Major mineralocorticoid is aldosterone
Stimuli:
- Activation of renin-angiotensin aldosterone system in response to reduced Na+ and low blood pressure
- Direct adrenal cortex stimulations from increased K+ concentration
34
Glucocorticoids
Metabolic Effects:
- Cortisol stimulates gluconeogenesis (glucose production from amino acids)
- Amino acids obtained from muscle protein degradation
- Cortisol inhibits glucose uptake and mobilizes lipid stores for a fuel source
Role in Adaptation to Stress:
- Cortisol causes a shift away from protein and fat stores while increasing carbohydrate stores
- This ensure adequate glucose supply for the brain during fasting
- Increased levels of AA, fatty acids and glucose aid in wound repair
35
Cortisol Secretion
- Secreted from the adrenal cortex and under negative feedback by the hypothalamus and anterior pituitary
Hypothalamus releases corticotropin releasing hormone (CRH), stimulating the pituitary to release adrenocorticotropic hormone (ACTH)
Other Influences:
- Diurnal rhythm secretion where highest cortisol level are in the morning and lowest at night
- Stress leads to a large increase in CRH release
36
The Adrenal Cortex and Sex Hormones
Androgens - considered male sex hormones
- majority produces in the testes
Estrogens - considered female sex hormones
- Majority produced in the ovaries
Adrenal cortex secretes insignificant amounts of androgens and estrogens
- Stimulated by ACTH
Most important adrenal cortex sex hormone is dehyroepiandrosterone (DHEA)
- in females it aids in pubic and armpit hair growth, puberty and female sex drive
37
Adrenal Medulla
Catecholamines synthesized by adrenomedullary secretory cells, and stored in chromaffin granules (similar to neurotransmitter vesicles)
- Chromafiin granules under exocytosis to release catecholamine
38
Adrenergic Receptors
- Norepinephrine predominantly release from nerve ending and bind to alpha and beta1 receptors near postganglionic sympathetic terminal
- Epinephrine released from adrenal medulla and activate all receptors, but exclusively activates beta 2 receptors.
39
Effects of Epinephrine
Organ Systems:
- During stress, the sympathetic nervous system mobilizes adrenomedullary and epinephrine system
- Increase heart rate, contraction strength, vasoconstriction, respiratory dilation
Metabolism:
- Increase blood glucose, liver gluconeogenisis, and glycogenolysis (breakdown of glycogen into glucose)
- Promotes lipolysis to increase energy source for heart and skeletal muscles
40
Integrates Stress Response
Sympathetic Nervous System and Epinephrine:
- SNS recruits the release of epinephrine from adrenal medulla
- Increase muscles strength, mental activity, blood pressure, metabolism, blood flow
Insulin and Glucagon:
- Increase glucagon secretion to break down glucose
CRH-ACTH-Cortisol System:
- Cortisol increases blood levels of glucose, free fatty acids and amino acids for energy and damage repair
- Beta-endorphin (natural morphine) produced when making ACTH
Renin-Angiostensin-Aldosterone System:
- Increase is vasopressin and angiotessin 2, which are vasoconstrictors
41
Hyperadrenalism
Cortisol Hypersecretion:
Cushing's Syndrome
- Overstimulation of adrenal cortex
- Adrenal tumours hypersecreting cortisol
- Symptoms are redistribution of fat in shoulder blade and oedema
Adrenal Androgen Hypersecretion:
- Adult females produce masculine body hair and increase in male secondary sex characteristics
- Little effect in adult males
- Newborn females have enlarges clitoris that looks lie a penis
- Prepubertal males have precocious pseudo puberty
Hyperaldosteronism:
- Excessive mineralocorticoid secretion from aldosterone secreting tumour (primary) or high activity in renin-angiotensin-aldosterone system (secondary)
42
Adrenocortical Insufficiency
- Dysfunction in both adrenal glands (one gland can compensate for the others dysfunction)
Primary Adrenocortical Insufficiency (Addison's Disease)
- Autoimmune destruction of the cortex
- Aldosterone and cortisol deficient
- Display hyperkalemia and hyponatremis (cardiac rhythms impacted)
Secondary adrenocortical insufficiency:
- Reduced ACTH from problem in anterior pituitary or hypothalamus
- Less nutrients in body (symptoms related to that)
43
Metabolism
synthesis, degradation, transport of substances into and between different cells, and transformation of
proteins, carbohydrates, and fats
- These are intermediary metabolism or fuel metabolism
Anabolic - synthesis
Catabolic - breakdown
44
Nutrient Storage
Excess Glucose:
- Stored in liver and skeletal muscles as glycogen
- Extra converted into fats and glycerol for make triglycerides in adipose tissue
Excess Fatty Acids:
- Stored as triglycerides
Excess Amino Acids
- used for structural proteins or converted to glucose and fatty acids
45
Metabolic States
Absorptive State:
- Anabolism dominates as ingested food is digested and absorbed
- Carbohydrates converted in the liver to glucose and stored as glycogen
- Fasts and proteins stored
Postabsorptive State:
- Catabolism dominates, several hours after ingesting food
- Glycogen stored in liver and skeletal muscles becomes energy source
- Lipolysis for energy
46
Other Energy Sources
Glycerol:
- Backbone of triglycerides that can be converted into glucose by the liver
Lactic Acid:
- Formed by glycolysis and can be converted to glucose
Ketone Bodies:
- Acetyl CoA (produced during citric acid cycle) converted to ketone bodies and release into the blood
- During starvations, can use bodies and energy source
47
The Pancreas
Exocrine and endocrine functions
- Endocrine functions are localized to the islets of langerhans cells
Alpha Cell: Produce and secrete glucagon
Beta Cell: Produce and secrete insulin
Delta Cell: Produce and secrete somatostatin
PP Cells: Secrete pancreatic polypeptide which reduces appetite
48
Somatostatin
Following a meal, the delta cells release somatostatin
- Slows down digestive system to inhibit digestion and absorption of nutrients
- Prevents the absorption of extra nutrients
Somatostatin is also produced in digestive tract lining as a paracrine hormone (effects were it is release)
- Released by hypothalamus where it inhibits GH and TSH
49
Insulin
Peptide hormone produced by beta cells of pancreatic islets
Effect on Carbohydrates:
- Increases the uptake of glucose into cells
- Inhibits glycogenolysis in the liver (Catabolism of glycogen)
- Stimulates glycogenesis in skeletal muscle and the liver
- Inhibits gluconeogenesis (glucose from AA) in the liver
Effect on Fats:
➢ Enhances the entry of fatty acids into adipose tissue cells
➢ Increases GLUT-4 recruitment in adipose cells to increase glucose uptake for the synthesis of triglycerides
➢ Enhances the activity of the enzymes involved in synthesizing triglycerides
➢ Inhibits lipolysis
Effect on Proteins
➢ Promotes the uptake of amino acids into all tissues.
➢ Enhances the activity of the enzymes involved in protein synthesis.
➢ Inhibits the degradation of proteins
50
Regulation of Insulin Secretion
Regulated by the plasma glucose level with negative feedback system
1. Elevated glucose levels cause the production and secretion of insulin. Promotes anabolism during absorption
2. Stimulated with a feedforward system when gastrointestinal hormones are release
3. Islets of langerhans are innervated by autonomic nervous system. parasympathetic cause insulin production and secretion
51
Glucagon
Pancreatic hormone involved during
state
- Triggered by decrease glucose levels
Effects on Carbohydrates:
- increases hepatic glucose production by decreasing glycogen synthesis, enhancing both glycogenolysis and gluconeogenesis
Effects on Fats:
- promotes lipolysis while inhibiting fat storage. It also enhances the formation of ketone bodies in the liver
Effects on Proteins:
- promotes protein catabolism but only in the liver
52
Insulin and Glucagon Together
Rise in blood amino acids stimulates release of insulin and glucagon
53
Growth
Two main growth periods:
- First two years of life
- Puberty
Until puberty growth between males and female is similar
- Men have more bone growth during puberty
Puberty growth supported by GH and androgens
54
Growth Hormone
Most abundant anterior pituitary hormone
Metabolic Actions of Growth Hormone:
1. Increased rate of protein synthesis
2. Increased fatty acid mobilization and use
3. Decreased rate of glucose use by body tissues
Soft Tissue Action of Growth Hormone:
- Increase thenumber of cells (hyperplasia) through stimulating cell division, or stimulate cells to grow larger (hypertrophy) by promoting protein synthesis
55
Bone and Bone Growth
Dynamic due to activity of two cell types:
1) osteoblasts that deposit new bone
2) osteoclasts that dissolve bone
Bone Growth in Thickness:
- Osteoblast deposit new bone on outer layer while osteoclasts remove internal bone to make marrow cavity
Bone Growth in Length
- Occurs between epiphysis and diaphysis in the epiphyseal plate
- Cartilage forming cells called chondrocytes divide and stack with newer cells at the epiphysis
55
Growth Hormone
Promotes thickness and length of bone
- effects of hormone mediated through peptides known as somatomedins (insulin-like growth factors)
Insulin Growth Factor 1:
- Growth hormones stimulate production of IGF-1 in liver and it has paracrine actions
Insulin Growth Factor 2:
- Important for fetal development
56
Growth Hormone: Regulation of Secretion
- Hypothalamus releases Growth hormone releasing hormone or growth hormone inhibiting hormone
- Anterior pituitary releases growth hormone
- Has diurnal pattern of secretion, High at night and low at day
57
Regulation of Calcium
Under hormonal control to ensure proper concentration and ingested in diet
Hormone regulators:
- Parathyroid hormone
- Calcitonin
- Vitamin D
58
Parathyroid Hormone
Produced in parathyroid which controls calcium levels
In the bones:
PTH causes more osteoclast activity than osteoblast, allowing the breakdown and release of calcium
In the Kidneys:
PTH causes reabsorption of calcium
59
Regulation of Parathyroid Hormone
Negative feedback
- More PTH release when calcium concentrations are high
60
Calcitonin
Release from thyroid gland
- Decrease osteoclasts and increased osteoblasts to decrease plasma calcium levels
61
Vitamin D
Hydroxyl group added to the vitamin D in the liver
- Causes the reabsorption of calcium in the intestines and kidney
PHGY 216
flashcards
Decks in class (4)
# Cards
