Neuroendocrinology Flashcards
1
Q
What is endocrinology?
A
The study of hormones, their receptors and their intracellular signaling pathways
2
Q
What are hormones?
A
Chemical messengers produced in one location and transported to a second location (target cells) where they exert their effects.
Hormones often reach their targets via the bloodstream.
3
Q
What concentrations do hormones usually act in?
A
Low concentrations
4
Q
What are the principle functions of the endocrine system?
A
Maintain homeostasis
Regulation of growth and development
Control energy storage and use
Mediate the body’s response to environmental cues
5
Q
What is autocrine?
A
Effect on itself.
Where the cell-produced substance has an effect on the cell by which it is secreted.
6
Q
What is paracrine?
A
Signalling cell having effect on the target cells only in the vicinity of the gland secreting it.
7
Q
What is endocrine?
A
Endocrine cells secrete hormone into the bloodstream - therefore have widespread effect.
8
Q
What is neurocrine?
A
Neurocrine is a type of chemical signaling that is facilitated by the neurons or nerve cells. The neuron’s release chemical messenger molecules called a neurotransmitter into their synaptic cleft which then diffuses across it and acts on its target cells.
(In bloodstream).
9
Q
What is the chemical classification of peptides?
A
Short protein chains of about 2 to 50 amino acids.
10
Q
What is the chemical classification of proteins?
A
A molecule made up of amino acids.
11
Q
What are amines derivates of?
A
Derivates of tyrosine amino acid.
12
Q
What are steroids synthesised from?
A
Synthesised from cholesterol
13
Q
What are prostaglandins synthesised from?
A
Synthesised from arachidonic acid
14
Q
What is synergy?
A
The effect of the combination of two or more substances being greater than that of their individual reactions combined.
15
Q
Name 11 important endocrine glands:
A
Hypothalamus
Pineal Gland
Pituitary
Thyroid
Parathyroid
Adrenal
Pancreas
Kidney
Ovaries (female)
Testes (male
Adipose Tissue
16
Q
Name 6 organs containing endocrine cells:
A
Thymus
Heart
Liver
Stomach
Kidney
Intestine
17
Q
What gland controls the circadian rhythm?
A
Pineal Gland
18
Q
What time of the day are bowel movements suppressed?
A
22:30 (10pm)
19
Q
What time of the day do we have highest coordination?
A
14:30 (2:30pm)
20
Q
What time of the day is our fasted reaction time?
A
15:30 (3:30pm)
21
Q
What time of the day is greatest cardiovascular efficiency and muscle strength?
A
17:00 (5:00pm)
22
Q
What time of the day is the highest body temperature?
A
19:00 (7:00pm)
23
Q
What time of the day does melatonin secretion start?
A
21:00 (9:00pm)
24
Q
What time of the night are we in our deepest sleep?
A
2:00am
25
What time is lowest body temperature?
4:30am
26
What time is the sharpest rise in blood pressure?
6:45am
27
What time does melatonin secretion stop?
7:30am
28
What time is bowel movement likely?
8:30am
29
What time is the highest testosterone secretion?
9:00am
30
What time is highest alertness?
10:00am
31
What is the hormone secreted by the pineal gland?
Melatonin
32
Where does the pineal gland secrete melatonin to?
Bloodstream
33
Where does melatonin feedback to?
The suprachiamatic nucleus (SCN) located in the hypothalamus.
34
What does melatonin act as?
Zeitgeber ("time-giver") - as it acts on the SCN where the circadian clock is located.
35
What are the functions of the hypothalamus and pituitary gland?
Water balance
Metabolism
Body growth
Reproduction
Milk secretion
36
What is the difference between the Anterior pituitary and posterior pituitary?
The anterior pituitary gland is connected to the brain by short blood vessels.
The posterior pituitary gland forms part of the hypothalamus/brain and secretes hormones directly into the bloodstream under the command of the brain. The PPG does not synthesise hormones itself but stores and secretes two hormones produced by the hypothalamus (oxytocin and antidiuretic hormone (ADH)/vasopressin).
37
What is the median eminence?
"window" of the brain - direct connection from brain to bloodstream
38
What are the six hormones produced by the hypothalamus?
CRH - Corticotropin-releasing hormone
TRH - thyroid releasing hormone
GnRH - Gonadotropin-releasing hormone
GHRH - Growth hormone releasing hormone
SS - Somatostatin
DA - Dopamine
39
What are the five hormones produced by the anterior pituitary?
ACTH - Adrenocorticotropic hormone
TSH - Thyroid stimulating hormone
LF/FSH - Follicle-stimulating hormone
GH - Growth hormone
PRL - Prolactin
40
What are the five peripheral target tissues of hypothalamus and pituitary axes?
Adrenal gland
Thyroid gland
Gonads
Liver and other
Breast
41
Do hypothalamus hormones have direct effects on the body?
No - they just release hormones that then have effects directly on the body (same for some anterior pituitary hormones).
42
What hypothalamus hormone excites ACTH?
CRH
43
What hypothalamus hormone excites TSH?
TRH
44
What hypothalamus hormone excites LH/FSH?
GnRH
45
What two hormones have an effect on GH?
GHRH - excites
SS - inhibits
46
What hormone inhibits PRL?
DA
47
What anterior pituitary hormone has its effect on the breasts?
PRL
48
What anterior pituitary hormone has effect on gonads?
LH/FSH
49
What anterior pituitary hormone has effect on thyroid gland ?
TSH
50
What anterior pituitary hormone has effect on Adrenal gland?
ACTH
51
What anterior pituitary hormone has effect on liver and other tissues?
GH
52
What does hypophysiotrophic hormone mean?
Means they have their effect on anterior pituitary gland.
53
What is the name of the cells that produce GH?
Samatrophs
54
Where are GHRH receptors located?
On the membrane of samatrophs
55
Is GH released from vesicles?
Yes - GH is released from vesicles inside the samatroph cells - exocytosis is stimulated by Ca2+ influx into the cell.
56
How does GHRH result in GH being released via exocytosis?
GHRH acts on GHRH receptors on the membrane of samatroph cells - this causes the production of adenyl cyclase --> cAMP --> PKA --> opening of Ca2+ channels --> influx of Ca2+ causes exocytosis of GH
57
How does SS inhibit GH release?
SS inhibits adenyl cyclase therefore PKS is not produced and Ca2+ channels not opened which stimulated exocytosis.
58
What does growth hormone (GH) stimulate?
Postnatal growth and development, metabolism and body composition
59
What is the pattern of GH secretion?
Bursts (pulsatile)
60
What type of hormone is GH?
Peptide hormone
61
What pattern of release does GH have?
diurnal (but not a true circadian rhythm - always being released but just elevated during the night)
62
What is the half life of GH in the blood?
20-25 minutes
63
How is GH transported in the blood?
Bound to growth hormone binding protein
64
What is GHRH stimulated by?
Exercise, stress, fasting, low glucose and sleep
65
What nucleus are GHRH neurons in?
Arcuate nucleus
66
What nucleus are somatostatin neurons in?
Periventricular nucleus
67
Where are magnocellular neurosecretory cells located?
Supraoptic and paraventricular nucleus of the hypothalamus.
68
What are the indirect growth effects of GH?
Stimulates the growth of bones, muscles and other tissues by stimulating cell division (mitogenesis) via insulin-like growth factor (INDIRECT).
69
What is the rate limiting reaction in the conversion of cholesterol into other hormones?
The removal of the p450 side chain
70
What are the direct growth effects of GH?
Stimulates protein synthesis in muscle (DIRECT).
71
What are the direct metabolic effects of GH?
Increases blood glucose by stimulating glucose synthesis (in liver) and inhibiting cellular uptake of glucose.
Increases triglyceride breakdown and free fatty acid mobilisation in adispose tissue.
72
What is giganticism a result of?
Excess GH production (generally caused by tumour of the pituitary)
73
Where are the neuron's of the posterior pituitary gland?
supraoptic and paraventricular nuclei
74
What are the two hormones secreted by the posterior pituitary gland?
Oxytocin and Vasopressin (anti-diuretic hormone)
75
What is Vasopressin (ADH) secreted in response to?
Increase plasma osmotic pressure or decreased blood volume
76
What does vasopressin inhibit?
urine production (diuresis) in the kidney
77
How does vasopressin increase blood pressure?
Vasoconstriction - cause blood vessel contraction
78
What does oxytocin act on?
Kidney to promote sodium excretion (natriuresis)
79
What does oxytocin do to the breasts?
milk ejection = Contracts mammary ducts for milk let-down during suckling
80
What effect does Oxytocin do during birth?
Causes uterine contraction
81
What is a disease caused by impaired or absent secretion of vasopressin?
Diabete insipidus (a disorder of salt and water metabolism marked by intense thirst and heavy urination)
82
What are the four zones of the adrenal gland cortex and what do they produce?
Capsule - doesn't produce hormones
Glomerulosa - produces aldosterone
Fasciculata = produces cortisol
Reticularis = produces androgens
| Can't Go For Run
83
What are the two zones of the adrenal gland?
Cortex (80%)
Medulla (20%)
84
What is the precursor of adrenal cortex hormones?
Cholesterol
85
What is cholesterol converted into when its side chain is removed?
Pregnenolone
86
What are glucocorticoids?
Cortisol
Corticosterone
87
What is a mineralocortcoid?
Aldosterone
88
What is the sex steroid precursor?
Androstenedione
89
What are the functions of aldosterone?
Acts to maintain fluid volume
Increases the reabsorption of sodium and water
Increase secretion of potassium
Increases water retention and therefore increases BP
90
What is the main site of action for aldosterone?
Kidney
91
What receptors do aldosterone bind to?
Mineralocorticoid receptors (MR)
92
What is HRE?
Hormone Response Element
93
What are ENaC, what activates them and what do they cause?
Epithelial Na+ Channel
They are activated by aldosterone (aldosterone is released from the adrenal gland and because it is a steroid hormone it freely diffuses into cells - typically cells of kidney collecting duct - it then binds to a receptor in the nucleus and causes transcription. As a result of transcription is the production of proteins that act as enzymes and activate ENaC and NaKAtpase).
Activation of ENaC causes an influx of Na+ into the cell and therefore creating an osmotic gradient and water moves from apical to interstitial side of the cell (follows electrolytes).
94
What ions are electrolytes?
Sodium and Potassium
95
Where are ENaC found?
In the collecting duct and distal tubules of membranes of kidney cells (these are sites that help reabsorb sodium ions from the urine back into the bloodstream).
96
What happens when aldosterone activates ENaC (in kidney collecting duct cells)?
ENaC allows for the selective transport of sodium ions from the tubular fluid into the interior of the epithelial cells lining the tubules (= causes sodium to move from extracellular space into the cell)
As sodium is actively transported into the cells they create a concentration gradient - with higher concentrations of sodium inside the cells compared to tubular fluid.
This creates an osmotic gradient, where water follows sodium ions passively
Ultimately it leads to increase sodium reabsorption and water retention.
97
What role does Renin have in control of aldosterone release?
Renin is a protein produced in the kidney.
It has an indirect effect in the aldosterone pathway - renin converts enzyme angiotensinogen produced by the liver into angiotensin 1.
A1 is then converted to A2 by an enzyme produced in the lungs.
A2 then acts on the adrenal gland.
98
When there is reduced extracellular fluid which hormone is secreted to retain water?
Aldosterone
99
What is the direct pathway of aldosterone release?
K+ increase directly leads to aldosterone secretion.
100
What is the more metabolically active glucocorticoid in the human body?
Cortisol
Corticosterone is less metabolically active.
101
How is cortisol synthesised and released?
Hypothalamic CRH stimulates the released of ACTH from the pituitary.
ACTH binds to MC2R on adrenal cortical cells. MC2R is a GPCR therefore leads to increase in cAMP and activation of PKA. This cascade results in enhanced expression of P450scc enzymes culminating in the increased synthesis and release of cortisol (cholesterol --> prenenolone --> cortisol).
102
How is CRH regulated (direct and indirect)?
ACTH directly inhibits CRH = direct
ACTH acts on the Adrenal gland which produces cortisol - cortisol inhibits ACTH and CRH = indirect
103
What is the main functions of cortisol in the body?
Generate glucose from the liver and other body substrates
Increase glucose production for energy by increasing gluconeogenesis and stimulates glycolysis
104
What are the functions of cortisol?
Generates glucose in the liver from other body substrates
Decreases bone formation and increases bone resorption
Decrease connective tissue
Inhibit inflammatory and immune responses
Maintain cardia output, increase arteriolar tone, decrease endothelial permeability
Facilitate maturation of the fetus
Increase glomerular filtration and free water clearance
Modulate emotional tone and wakefulness
Maintain muscle function and decrease muscle mass
105
What produces catecholamines (epinephrine / norepinephrine)?
Adrenal Medulla
106
What other things does adrenaline do?
Effect on the heart - increased cardiac contractility and increased heart rate
Dilates smooth muscle around the arterioles
Constricts other arterioles
107
What is the main effect of adrenaline?
Shunts blood to exercising muscles and the brain and away from other tissues.
108
What are the metabolic effects of adrenaline?
Similar to cortisol:
Glucose increase in blood
Reduces secretion of insulin and the action of insulin on increasing glucose uptake into the tissue
109
What is stress?
Stress is the sum of biological reactions to any adverse stimulus - physical, mental or emotional, external or internal, that disturbs homeostasis.
110
What is the stimulus for stress called?
stressor
111
Biologically what is stress?
Events that cause an increase in cortisol secretion
112
What is the first thing produced in response to stress?
Adrenaline (through sympathetic nervous system).
113
What does adrendaline (the fight or flight acute stress response) cause?
VASULAR CHANGES
114
What does cortisol cause?
ENERGY MOBILIZATION
115
Under fasting/stress conditions what causes blood glucose to increase?
Cortisol stimulating gluconeogenesis in the liver
Cortisol inhibiting glucose uptake by muscle and adipose cells
Cortisol promoting protein breakdown in skeletal muscle, fatty acids in adipose tissue to supply fuel for glucose synthesis.
116
What releases cortisol?
Adrenal cortex
117
What is the first thing released in the fight or flight response for stress?
Adrenaline - only an increase in cortisol release from chronic stress (sustained stress)
118
What are the risks of chronic stress (chronically elevated cortisol)?
Decrease immune function
Increase risk of infection and cancer
Worsens diabetes due to anti-insulin effects
Possibly increase neuronal death rate
Might enhance arthrosclerosis and hypertension
Induces infertility
Decrease bone density
## Footnote
Do I Want People Memorising Intimate Details
119
What is the energy consumption of carbohydrates?
17kJ/g
120
What is the energy consumption of protein?
17kJ/g
121
What is the energy consumption of fat?
37kJ/g
122
What are the units of energy?
kJ/g
123
What are four key ways of energy expenditure?
Basal metabolic rate
Thermogenesis
Locomotion
Growth
124
What is hypoglycaemia?
Low glucose
Causes decrease CNS function, coma, death
125
What is hyperglycaemia?
High glucose
Causes osmotic diuresis, dehydration, vascular collapse, death
126
What is the principle circulating sugar in the blood and the major energy source in the body?
Glucose
127
What do we approximately want blood glucose levels to be at?
4-6 mM
128
What is glycolysis?
The process of glucose that is consumed from food being converted into Pyruvic acid.
Process involves using 2 ADP + 2 Pi to covert the glucose into 2 ATP to make pyruvic acid.
129
What happens to pyruvic acid if there is no oxygen available?
Anaerobic fermentation - lactic acid is produced.
130
What is aerobic respiration of pyruvic acid?
Process when oxygen is available of converting pyruvic acid into lots and lots of ATP through there Kreb's Cycle.
131
Where does the Kreb's cycle occur?
Mitochondrion
132
How many ATP molecules can be produced from 1 glucose molecule?
38
133
Can we create energy?
No - we cannot create energy we just transfer it from one form to another.
134
What is the absorptive state?
When food is available and we have just consumed glucose.
135
What is the post-absorptive state?
When no food valuable so using stored energy
136
What is glucose stored as and where?
Glycogen stored in the liver.
137
What is glycogenolysis?
Glycogenolysis is the process by which glycogen, (stored glucose in the liver and muscle cells) is BROKEN DOWN into glucose to provide immediate energy and to maintain blood glucose levels during fasting.
138
What is gluconeogenesis?
The process in which glucose is FORMED from noncarbohydrate sources, such as lactate, amino acids, and glycerol.
139
Does anabolic or catabolic refer to high insulin?
Anabolic (anabolic refers to making sure there is enough energy stored).
140
Does anabolic or catabolic refer to high glucagon?
Catabolic (glucagon is broken down into glucose to provide energy)
141
What is the difference between anabolic and catabolic?
Anabolism is the building of complex molecules from numerous simple ones. Think of protein synthesis.
Catabolism is the breakdown of complex molecules into numerous simple ones. Think the break down of glucose.
142
What role does the pancreas have in relation to glucose in the body?
It produces and secretes two key hormones: insulin and glucagon which control glucose homeostasis.
143
What pancreas cells secrete insulin, glucagon and somatostatin?
beta cells = insulin
alpha cells = glucagon
gamma cells = somatostatin
144
What are the Islets of Langerhans?
They are the pancreatic cells that produces hormones (insulin and glucagon).
145
What portion of the pancreas glands are exocrine?
98% exocrine (2% endocrine)
Exocrine meaning produce enzymes for digestion
146
What is the difference between exocrine and endocrine pancreas glands?
The pancreas has both exocrine and endocrine functions.
Exocrine = the secretion of digestive enzymes into the pancreatic ducts and into digestive tract.
Endocrine = secretion of hormones from islets of Langerhans directly into the bloodstream to regulate blood glucose levels and other metabolic processes.
147
What happens when there is an increase in plasma glucose?
Pancreatic islet beta cells increase insulin secretion
Plasma insulin increases
Adipocytes and muscles increase glucose uptake and liver stops glucose output.
= Restoration of plasma glucose
148
What does insulin released into the bloodstream bind to?
Insulin receptor = Tyrosine Kinase.
Tyrosine Kinases have intracellular domains - when insulin binds they are phosphorylated.
149
Are insulin receptors (tyrosine kinases) a type of GPCR?
No - they have intracellular domains which are automatically phosphorylated when insulin binds (whereas in GPCR when signalling molecule binds there is a cascade of events not autophosphorylisation)
150
What does an activated tyrosine kinase activate?
Insulin receptor substrate - which then acts on a glucose transporters that allows glucose to enter the cell.
151
What causes the release of insulin once glucose enters a beta cell?
Glucose is transported into the beta cell via GLUT2.
Inside the cell glucose acts on glucokinase.
NADPH is produced which leads to opening of K+ and Ca2+ channels
An influx of Ca2+ into the cell causes granules filled with stored insulin to be released (exocytosis like).
152
What is the glucose transporter for beta cells?
GLUT2
153
What is the glucose transporter used by muscle cells to uptake glucose?
GLUT4
154
What hormones modulate the release of Insulin from beta cells?
Somatostatin by inhibiting protein kinase A - preventing insulin release.
AND
GLP and GLP-1 which stimulate kinase A - stimulating insulin release.
+
CCK Acetyl-choline
155
Where are GLP and GLP-1 secreted from?
Intestines
156
What is the incretin effect?
The incretin effect refers to enhanced insulin secretion when glucose is ingested orally compared to when it is administered intravenously, despite the same blood glucose levels.
This is due to incretin hormones like GLP-1 (Glucagon-like peptide-1) and GIP (Glucose-dependent insulinotropic peptide), which are released from the gut in response to food intake and enhance insulin secretion.
These incretin hormones enhance the effect of glucose on insulin release, leading to a more substantial insulin response after oral intake of glucose compared to intravenous administration.
157
Does insulin increase or decrease glucose levels?
Decrease
158
Does glucagon increase or decrease glucose levels?
Increase
159
What type of hormone is glucagon?
peptide hormone
160
How does the release of glucagon from pacretic alpha cells increase plasma glucose?
Increases glycogenolysis
Increases gluconeogenesis
Increases ketone synthesis
161
What is pathway that mediates glucagon action?
Glucagon binds to a specific glucagon GPCR and activates it by converting GDP to GTP.
Activated GPCR then activates adenylate cyclase.
This increases the levels of cAMP (from ATP), which in turn activates Protein Kinase A (PKA).
PKA causes phorphoylation leading to various downstream effects that ultimately increase blood glucose levels (gluconeolysis and gluconeogenesis).
162
What happens when plasma glucose levels decrease?
Pancreatic islet alpha cells increase glucagon secretion
Plasma glucagon increases
Liver increase glycogenolysis, gluconeogenesis and ketone synthesis.
= increase plasma glucose and also plasma ketones.
163
What is type 1 diabetes?
A loss of beta cells in the pancreas leading to a deficiency in insulin.
164
What is type 2 diabetes?
A resistance against insulin or reduced insulin sensitivity.
165
How is the hypothalamus related to insulin action?
The brain controls the liver therefore the stores of glucose.
166
Where is the thyroid gland located in the body?
The thyroid gland is found at the front of the neck, under the voice box. It is butterfly-shaped: The two lobes on either side lie against and around the windpipe (trachea), and are connected at the front by a narrow strip of tissue known as the isthmus.
167
What are the two hormones produced by the thyroid gland?
T3 (Triiodothyronine) and T4 (Thyroxine).
168
Is T3 or T4 more metabolically active?
T3
169
Explain the intracellular process of thyroid hormones that results in increase O2 consumption and increased metabolic rate:
T4 is converted into T3 in the cytoplasm.
T3 enters the nucleus and binds to thyroid hormones receptors (TR) that are associated with thyroid response elements (TRE) on DNA.
The binding of T3 to TR on TRE leads to changes in gene expression, resulting in the production of messenger RNA (mRNA).
mRNA translates into proteins that are essential for growth and maturation.
This process also increases the synthesis of various enzymes and proteins, including those involved in mitochondrial respiratory functions and Na⁺,K⁺-ATPase.
The increased production of these enzymes and proteins enhances mitochondrial activity, leading to greater oxygen (O₂) consumption. The overall metabolic rate of the cell is increased.
170
What are in the metabolic effects of thyroid hormone?
increased CO2, ventilation, urea, renal function, thermogenesis, sweating, and weater loss
decreased muscle mass and adipose tissue
171
What are the oxygenic effects of thyroid hormone?
increase cardiac output, ventilation, food intake and mobilisation of endogenous carbohydrates, protein and fat.
172
What is the essential element required for thyroid hormone production?
Iodine
173
What is hypothyroidism and the type types of conditions it can cause?
Hypothyroidism = Low thyroid hormone production.
Can be due to an iodine deficiency causing the thyroid to be enlarged (goiter condition) or an autoimmune disease where the body attacks the thyroid causing it to shrink (Hashimoto disease).
174
What does high levels of T3 and T4 result in?
Inhibition of TSH production
175
What is hyperthyroidism?
Hyperthyroidism = High levels of thyroid hormones.
Typically only caused by an autoimmune disease that attacks the thyroid but acts in a different way (it is the only autoimmune disease known to not result in tissue destruction) - it stimulates the receptor that TSH bind to. Therefore it results in artificial stimulation resulting in more thyroid hormone.
Some people with the autoimmune disease will develop graves disease.
176
How is body weight regulated?
The balance between energy consumption (food) and energy expenditure (body activity and exercise).
Energy consumption = carbs, protein and fat.
Energy expenditure = basal metabolic rate, thermogenesis, locomotion and growth (exercise increases these things).
177
What is the approximate difference between consumed and spent energy regulated naturally by our body?
0.2% (99.8%)
178
How is BMI calculated?
Body weight in kg divided by heigh in meters squared.
179
What is one way that nutrition plays a role in obesity?
Frutose
180
What are two food types that fructose is added to?
Soft drinks and fast food/prepacked meals
181
What are possible effects of fructose?
Insulin resistance and diabetes
Increase in triglycerides
Liver steatosis
Tumour cells can metabolise fructose better than other sugars.
182
What are the two components that can cause obesity?
Environmental (e.g., the food you eat such as fructose consumption)
Genetics
183
What part of the body regulates body weight?
Hypothalamus
184
What is Leptin?
Leptin is a hormone predominantly produced by adipose (fat) tissue. It plays a key role in regulating energy balance by inhibiting hunger, which in turn helps to regulate body weight.
185
Where does leptin bind?
Leptin circulates in the blood and binds to receptors in the hypothalamus.
186
What isoform of the leptin receptor can relay signals intracellularly?
Long isoforms = Ob-Rb
187
How does Leptin result in reduces body weight?
Excess energy is stored in adipose tissue (fat) - as fat increases leptin secretion into the bloodstream is increased.
Leptin travels in the bloodstream and reaches the hypothalamus binding to its specific receptors.
Once it binds to receptors it alters the activity of integrating centers that control hunger and energy expenditure. The hypothalamus responds to higher leptin levels by reducing appetite (lowering energy intake). It also increases metabolic rate, which enhances energy expenditure.
Over times these changes can lead to a negative energy balance, ultimately resulting in reduced body weight.
188
What are 99% of obese humans resistant to?
Leptin - with too much leptin body doesn't know what to do with it so it become inefficient at reducing appeitite.
189
Does leptin act directly?
No - it is a signalling protein.
190
What is SOCS3 role in leptin signalling?
SOCS3 is the key negative regulator of leptin signalling - inhibits the leptin negative feedback pathway, contributing to leptin resistance.
191
What happens after leptin binds to its receptor in the hypothalamus?
Stimulates transcription factor and produces STAT3.
STAT3 goes to the cell nucleus and produces SOCS3.
SOCS3 inhibits the leptin cascade.
192
What other anorexigenic hormones regulate body weight?
CCK and PYY
193
What does anorexigenic mean?
Hormones that reduce appetite.
194
What does orexigenic mean?
Hormones that increase appetite.
195
What is Ghrelin?
The "hunger hormone".
It is a peptide hormones that is secreted by endocrine cells in the fundus of stomach.
It stimulates hunger, food intake, gastric emptying and growth hormone secretion bay the pituitary.
196
What is Ghrelin increased by?
Fasting and a low calorie diet
197
What reduces Ghrelin concentrations in the blood?
Obesity
198
What does Ghrelin suppress?
Fat utilisation in adipose tissue.
199
When are Ghrelin levels high?
Before meals (breakfast, lunch and dinner times).
200
What are the two neuron types in the hypothalamus that modulate eating?
NPY
POMC
201
Does NPY stimulate or inhibit eating?
Stimulates
202
What hormone is NPY stimulated by?
Ghrelin
203
Does POMC stimulate or inhibit eating?
Inhibits
204
What hormones stimulates POMC?
Leptin
205
What hormone inhibits NPY?
Leptin
206
Does Ghrelin act on POMC?
No
207
What is secreted from the hypothalamus that is involved in the hormone control of male and female reproduction and what does it cause to be released from the Anterior Pituitary?
GnRH --> cause FSH and LH to be produced and secreted from anterior pituitary.
208
What is gametogenesis?
Sperm production in the testes and ova development in the ovary
209
What is steroidogenesis?
Hormone production
Males = testosterone and inhibin
Females = estrogen, progesterone and inhibin
210
What is the hypothalamus-Pituitary-Gonadal axis?
The HPG is the pathway between hypothalamus and anterior pituarty.
GnRH neurons cell bodies in Hypothalamus and project to synapse on AP.
211
What are the two key cell types in spermatogenesis (sperm production)?
Leydig cells
Sertoli cells
212
What do Leydig cells do?
Produces testosterone (by synthesising cholesterol).
This testosterone is then converted into sertoil cells to be converted into estrogen (by using the aramotase enzyme that is only found in Sertoli cells).
213
What do Sertoli cells do?
Support cells
Produce inhibin and estrogen - Testosterone produced by L cells is locally transported to S cells and S cells convert it to estrogen.
Estrogen is then taken into Lydia cells to promote testosterone synthesis from cholesterol.
214
What enzyme is in Sertoli cells that allows it to convert testosterone into estrogen?
Aromatase
215
What causes the production of aromatase?
Activation of FSH.
216
Where does sperm production occur?
Seminiferous tubules
217
Where is sperm stored?
Epidiymis
218
Explain the hormonal control feed back loop of male reproduction:
Hypothalamus secretes GnRH
GnRH feeds back to Anterior Pituitary causing it to secrete FSH and/or LH
LH acts on leydig cells = testosterone released into bloodstream and acts on other organs + feeds back to AP to inhibit LH production and to Hypothalamus to inhibit GnRH production.
FSH acts on Sertoli cells = inhibin released which feeds back to inhibit FSH secretion and also stimulate spermatogenesis.
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What happens to estradiol produced in S cells?
It can be transported to L cells and used from new protein synthesis.
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Testosterone in target cell cytoplasm can be converted into more active forms - what enzyme is required for this synthesis?
5alpha-reductase
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When is testosterone levels highest in males?
Around 6am till noon.
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When does testosterone peak in the lifetime of a male?
Between 3-6 months of fertilisation
Just after Birth
From puberty till around 60 years old
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What are the key anatomical components of the female reproductive system?
Fallopian tube
Ovary
Endometrium
Uterus
Myometrium
Cervix
Vagina
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Was is the follicular development?
Primordial follicle --> primary follicle --> secondary follicle --> mature follicle (tertiary follicle --> ovulation --> corpora lutea --> corpus albicano --> arterite follicle
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What is Atresia?
Death of follicle.
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What is the corpus luteum and what does it secrete?
The corpus luteum is a temporary collection of cells that forms on your ovary each menstrual cycle if you're still getting a menstrual period. It appears right after an egg leaves your ovary (ovulation). The corpus luteum's job is to make your uterus a healthy place for a fetus to grow.
It secretes estrogen, progesterone and inhibin.
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If ovulation does not occur when will the corpus luteum degenerate?
after approx 10 days
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What does the degeneration of the corpus luteum cause?
Menstruation
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What is the follicular phase?
Follicle development prior to ovulation
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What is the luteal phase?
Corpus luteum active after ovulation
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What is the hormonal control feed back loop of a female in early and middle follicular phase?
Hypothalamus secretes GnRH which acts on AP
Ap secretes FSH and LH
FSH acts on granulosa cells = inhibin released which inhibits release of FSH (primarily but not exclusively like in males)
LH acts on theca cells = androgen release = androgen converted into estrogen.
Estrogen inhibits LH and GnRH
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What are the two key cells of the female reproductive system?
Granulosa cells
Theca cells
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Which females cell doesn't have aromatase?
Theca Cells
Aaromatase is required to produce estrogen therefore theca cells do not produce estrogen - they produce androgens / progesterone.
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How is estrodiol produced in granulosa cells?
Cholesterol ---> pre and postgesterone.
Postgesterone using 17a-hyrooxylase converted into androstenedione
(Androstenedione taken into Theca cells to be converted into testosterone).
Androstenedione in granulosa cells uses aromatase to produce testosterone and estrone --> aromatase used to convert into estradiol.
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What ovarian cycle phase is the corpus luteum produced?
Luteal phase
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Approximately when does does ovulation occur?
Day 14
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When in the ovarian and menstrual cycles does basal body temperature increase?
Day 14-28 = during the luteal phase
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What is the hormonal trigger for ovulation?
Estrogen switching to a positive feedback = No longer inhibits production of FSH and LH and excited LH production = LH surge and ovulation occurs.
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When is the negative feedback restored after the Estogen switch?
When the corpus luteum degenerates so estrogen and progesterone decrease.
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What are the 12 changes in hormonal levels during the menstrual cycle?
(1) Low estrogen = LH and FSH increase so multiple follicles develop
(2) estrogen from follicles rises
(3) dominant follicle secretes estrogen and inhibin
(4) increased estrogen and inhibin reduce FSh
(5) = estrogen switch to positive feedback
(6) LH Surge
(7) Corpus luteum forms
(9) corpus luteum secretes estrogen and progesterone
(10) FSH and LH are inhibited
(11) Corpus luteum degenerates so estrogen and progesterone decrease
(12) FSH and Lh levels rise
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What causes the estrogen switch?
Largely unknown but thought to be kisspeptin acting on the hypothalamus
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What does oral contraception pills containing synthetic estrogen and progesterone do?
Prevent ovulation by maintaining negative feedback - make uterus les likely to accept implantation by thickening the mucus in the cervix.
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What are side effects to oral contraception?
Coagulation (clotting)
Increase risk of deep vein thrombosis (DVT)
pulmonary embolism
Stroke
Myocardial infraction (heart attack)
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Where is the embryo located?
Amniotic sac
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What causes the cervic to become soft and flexible in the last few weeks before pregnancy?
Breakup of collagen fibres
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What ruptures at the onset of labor ("water breaking")?
The amniotic sac
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Why makes coordination of preganacy contractions possible?
Gap junctions between smooth muscle cells increasing near the end of pregnancy
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What does oxytocin do?
Acts on muscle to allow for milk ejection
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How is prolactin secreted
Sucking of breast causing mechanicorecptors to be activated and causing negative feed back that reduces dopamine production (tubers-infundibular dopamine neurons) stopping the inhibition of prolactin - prolactin produced and secreted and acts on breasts to product milk.
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What does prolactin do?
Causes milk synthesis.
251
Define these terms: glucose, glycogen, glucagon, insulin and somatostatin.
Glucose = sugar in your blood (get it from food)
Glycogen = glucose broken down and stored for later energy use
Glucagon = hormone that triggers the release of glycogen back into bloodstream when you need it (increase blood glucose)
Insulin = hormone produced by pancreas beta cells that stores glucose in cells as glucagon
Somatostatin = inhibitor hormone
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When does a zygote (fertilised egg) become an embryo?
Between day 4-7 after fertilisation
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What are the cells of a zygote called during the cleavage stage (day 1-4 after fertilisation)?
All cells are totipotent meaning they can become anything at this stage.
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What is the blastocyst stage?
Day 4-7 after fertilisation - it is when the cells start to differentiate.
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What do cells differentiate into during the blastocyst stage of early embryonic development?
1) Trophoblasts = the outer layer of the embryo. These cells are used from embryonic nutrient and release pregnancy hormones.
2) Inner cell mass = these cells will develop into the embryo and then later the fetus.
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What happens on day 7 after fertilisation?
Implantation = the blastocyst embeds itself into the endometrium which is the lining of the uterus.
257
Define glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis
Glycolysis is glucose --> ATP
Gluconeogenesis is non-carbohydrates --> glucose
Glucogenesis is glucose --> glycogen
Glycogenolysis is glycogen --> glucose
258
Once GH acts on the liver how are GHRH and SS affected?
The liver produces insulin-like growth factor which inhibits GHRH (preventing the release of GH) and excites SS (increased inhibition of adenylic cyclase).
259
How many kJ are needed to gain 250g?
6.351 kJ (or 1.560 kcal)
