Neurohormones Flashcards
(89 cards)
1
Q
What are neurohormones?
A
Compound neurotransmitters that are released from the brain neurons, not into the synapse, directly into the blood circulation.
2
Q
How do neurohormones act?
A
They circulate around the blood and diffuse out of the capillaries and act on receptors for the neurohormone. It can have a potential widespread effect all around the body.
3
Q
What are the two main control systems in the body?
A
- Endocrine system
- Nervous system
4
Q
How does the endocrine system work?
A
- Mediators travel within blood vessels
- Utilises chemical mediators (hormones)
- Slow communication
- Effects can be long-lasting
5
Q
How does the nervous system work?
A
- Signalling along nerve fibres
- Transmission of electrical impulses
- Fast communication
- Effects are generally short-acting
6
Q
Which cells produce neurohormones?
A
Produced by specialised nerve cells called neurosecretory cells and released into the blood.
7
Q
Why are neurohormones defined as hormones?
A
They are defined as hormones as they are secreted into the blood and have their effect on cells some distance away.
8
Q
What is different about neurohormones and normal hormones?
A
They can also act as neurotransmitters or as autocrine (self) or paracrine (local) messengers
9
Q
What are the three types of hormones?
A
- Protein and peptide hormones
- Amino acid derivatives
- Steroid hormones
10
Q
Protein and peptide hormones
A
- Vary considerably in size
- Can be synthesised as a larger precursor and processed prior to secretion (e.g. GH, somatostatin, insulin)
- Can be post-translationally modified (e.g. Glycosylation)
- Can have multiple subunits synthesised independently and assembled (e.g. FSH, LH, TSH)
11
Q
Amino acid derivatives
A
- Mostly tyrosine derived
- Neurotransmitter that can also act as a hormone
- E.g. epinephrine, norepinephrine and dopamine
12
Q
Steroid hormones
A
- Steroid is a class of lipids derived from cholesterol
- Include cortisol, aldosterone, testosterone, progesterone, oestradiol
13
Q
What are the principle endocrine organs of the body?
A
- Hypothalamus
- Pituitary gland
- Thyroid gland
- Parathyroid glands
- Adrenal gland
- Pancreas
- Ovary
- Testes
14
Q
What hormones does the hypothalamus release?
A
Thyrotrophin-releasing hormone, GnRH, CRH, GHRH, Prolactin-inhibiting factor (dopamine), somatostatin
15
Q
What hormones is released from the anterior pit?
A
Thyroid-stimulating hormone, LH, FHS, GH, Prolactin and adrenocorticotrophin
16
Q
WHat hormones are released from the posterior pit?
A
Vasopressin and Oxytocin
17
Q
Hormones released from thyroid gland
A
Thyroxine
Triiodothyronine
Calcitonin
18
Q
Hormones released from parathyroid glands
A
PTH
19
Q
Hormones released from adrenal cortex of adrenal gland
A
Aldosterone
Cortisol
20
Q
Hormones released from adrenal medulla of adrenal gland
A
Adrenaline
Noradrenaline
21
Q
Hormones from pancreas
A
Insulin
Glucagon
Somatostatin
22
Q
Hormones from ovary
A
Oestrogen
Progesterone
23
Q
Hormones from testes
A
Testosterone
24
Q
Where are neuropeptides most important?
A
They are functionally important transmitters in the hypothalamo-pituitary axis
25
What are the two components of the HPA?
Anterior and posterior pituitary
26
What is the capillary network system in the hypothalamus?
The hypophyseal portal circulation - this connects to another portal system in the anterior pituitary.
27
How does the hypophyseal portal circulation work with the neurohormones?
- There are neurons that project and release neurohormones directly into the portal system in the hypothalamus.
- Once released, the neurohormones are transported along the system and activate receptors in the anterior pituitary which release other neurohormones into blood circulation.
- These are circulated throughout the body and activate other receptors
28
How is the posterior pituitary connected to the hypothalamus differently?
It is connected through neurons called magnocellular neurons that project from the hypothalamus directly to the posterior pituitary. This is called the hypophyseal nerve tract.
29
Why type of rhymthms are most endocrine hormones?
Periodic rhythms
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Circadian rhythms
- Based on a 24-hour cycle
- Example: secretion of cortisol, GH, PRL
- Blood cortisol levels fluctuate throughout the day - it's highest in the morning and decreases after this. Before bed, there is another increase.
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Pulsatile (ultradian) rhythms
- Periodicity of less 24 hours (usually 1/2-2 hours)
| - e.g. secretion of gonadotrophins in adults
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Infradian rhythms
Periodicity longer than 24 hours e.g. Menstrual cycle
33
Where are the neuroendocrine secretory cells?
Scatted in the hypothalamus but key nuclei are the medial pre-optic, the arcuate and the paraventricular nuclei
34
What are the hypothalamic neurohormones that control the anterior pituitary?
- Corticotrophin Releasing Hormone (CRH)
- Thyrotrophin releasing hormone (TRH)
- Gonadotrophin Releasing Hormone (GnRH)
- Growth Hormone Releasing Hormone (GHRH)
- Growth Hormone Releasing Inhibiting Hormone (Somatostatin)
- Dopamine
35
What is the CRH?
41 amino acid peptide that controls the release of adrenocorticotrophin (ACTH)
36
What is thyrotrophin releasing hormone (TRH)?
- 3 amino acid peptide that controls the release of thyroid stimulating hormone (TSH) and prolactin (PRL)
- Thyrotrophins that regulate TSH secretion in response to TRH.
- Lactotrophs that control the secretion of prolactin in response to TRH, somatostatin and dopamine.
37
What is Gonadotrophin Releasing Hormone (GnRH)?
- 10 amino acid peptide that controls the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH).
- Gonadotroph cells that secrete LH and FSH in response to GnRH
38
What is growth hormone releasing hormone (GHRH)?
- 44 amino acid peptide that controls the release of growth hormone (GH).
- Somatotrophs that control GH secretion in response to GHRH.
39
What is growth hormone release inhibiting hormone (somatostatin)?
- 14 amino acid peptide that inhibits the release of GH, gastrin, vasoactive intestinal polypeptide (VIP), glucagon, insulin, TSH and PRL.
40
What is dopamine?
A monoamine that inhibits the release of PRL.
41
What factor can activate the hypothalamic-pituitary adrenal axis?
Stress
42
How is adrenocorticotrophic hormone (ACTH) released when it is under stress?
- The hypothalamus will release corticotrophin releasing hormone (CRH).
- Then, it will cause the anterior pituitray to release ACTH.
- It is released into the blood circualtion and act on ACTH receptors on the zona fasciculata of adrenal cortex to release cortisol.
43
Role of cortisol
Cortisol mobilises energy to allow for 'protection'.
44
How does cortisol work?
- Cortiol produces a negative feedback effect.
- When circulating, it will act on cortisol receptors in the pituitary or hypothalamus to inhibit the release of ACTH or CRH.
- This is entirely physiological.
45
What happens when cortisol release doesn't go down?
If high for a prolonged period of time e.g. peroids of chronic stress, then there is hypersensitivity of HPA axis which will lead to high levels of basal cortisol levels.
46
Structure of ACTH
39 amino acid peptide with a molecular weight of 4.5 kDa.
47
What does ACTH derive from?
Belongs to a family of related peptide hormones derived from a large precursor glycoprotein, pro-opiomelanocortin (POMC).
48
What does the HPA axis modulate?
It modulates stress activity - any dysfunction will cause a problem.
49
Describe the production of T3
- Thyrotrophic releasing hormone (TRH) from the hypothalamus stimulates the anterior pituitray to release thyroid-stimulating hormone (TSH).
- TSH acts on the thyroid to increase T4/T3 secretion. T3 is the most potent thyroid hormone and target tissues containing a deiodinase enzyme (DI) to convert T4 to T3.
- The pituitary also expresses deiodinase to convert T4 to T3 to facilitate negative feedback.
50
What controls the regulation of TSH and thyroid secretion by negative feedback?
Under normal conditions, there will be negative feedback response which will inhibit the release of the neurohormones. The release of T3 will cause less TRH from the hypothalamus.
51
What happens when the secretion of TSH isn't regulated?
- It can cause hyperthyroidsim.
- It can cause anxiety as high levels of thyroxine is released.
- Too low levels causes low energy, weight gain, behavioural changes can cause cognitive impairment.
52
What is prolactin? What does prolactin do?
Protein released from the lactotrophs in the anterior pituitary.
53
Function of prolactin
- It increases milk production by stimulating the mammary gland development during puberty.
- It maintains lactation (synergised by glucocorticoids, inhibiting by oestrogen and progesterone - decrease of both after parturition).
54
What inhibits prolactin release?
Dopamine from the hypothalamus
55
Structure of prolactin
A 199 amino acid protein with molecular weight of 22kDa and contains three disulphide bonds.
56
Which neurons release vasopressin and oxytocin?
Magnocellular neurons from the hypothalamic neurohormones.
57
Structure of the vasopressin and oxytocin
Simple peptides only 9 amino acids - only 2 amino acids different at position 3 and 8.
Structurally quite similar, yet have very different functions.
58
Where is vasopressin and oxytocin synthesised?
It is synthesised in the supraoptic and paraventricular nuclei in the hypothalamus.
59
How is vasopressin and oxytocin transported?
It is transported to the terminals of the nerve fibres located in the posterior pituitary.
60
What is vasopressin? Function of vasopressin
- Also known as anti-diuretic hormone (ADH)
- Release is stimulated by changes in the activity of the osmoreceptor complex in the hypothalamus
- Controls plasma osmolality by regulating water excretion and drinking behaviour
- Stimulates vascular smooth muscle contraction in the distal tubules of the kidney to reduce loss of water and raise blood pressure.
61
What is oxytocin? Function of oxytocin
- Acts on oxytocin receptors that are found on the uterus.
- Induces uterine contraction
- Normally, undetectable, but elevated during parturition, lactation and mating.
- Released in response to peripheral stimuli of the cervical stretch receptors and suckling at the breast.
- May also be involved in responses to stroking, caressing, grooming
- Regulates contraction of smooth muscles (e.g. uterus during labour, myoepithelial cells lining the mammary duct, contraction of reproductive tract during sperm ejaculation).
62
Describe the RAAS
In response to thirst, or excessive blood loss where blood pressure needs to be increased. The kidney starts to release an important enzyme called renin. This breaks down angiotensinogen found in the liver to angiotensin I. This is converted to angiotensin II by ACE.
63
What is the function of Angiotensin II?
Constricts the blood vessels to increase the blood pressure.
64
What detects angiotensin II?
Detected by the subfornical organ that sends a signal to the vasopressin cells and neurons in the lateral hypothalamus to release vasopressin from the pituitary.
65
Function of oxytocin in uterine contractions
When the baby pushes the uterus to stretch, this causes the stimulation of neurons which will send signals to the magnocellular neurons to release oxytocin.
It is released in the blood circulation and acts on receptors in the uterus to cause uterine contraction. The baby starts to move forwards, stretching the uterus more - this is an example of positive feedback. This causes the release of more oxytocin.
66
Where else does oxytocin act?
The magnocellular neurons project to other regions of the brain such as the hypothalamus, the olfactory region, the reward centres, the amygdala. There are oxytocinergic projects in the brain - not peripheral.
67
What is the function of oxytocin in the brain?
Social bonding - love hormone.
Mental health conditions are characterised by social impairment for example, anxiety, schizophrenia, autism. This shows the importance of oxytocin as a social hormone.
68
Tyrosine kinase mechanism and neurohormones (GH)
- GH induces the effect by acting on tyrosine kinase growth hormone receptors.
- Causes dimerisation of the receptors, subsequently recruiting tyrosine kinases (JAK2 or MAPK) which phosphorylates the target protein (STAT) to induce biological responses.
69
What happens if there is a mutation in the GH receptor gene?
It can result in defective hormone binding or reduced efficiency of receptor dimerisation -> GH resistance "Laron syndrome"
70
What is laron syndrome?
GH resistance
71
Examples of hormones that act on GPC receptors
TSH and ACTH
72
What happens when neurohormones bind to GPCR?
Results in a conformational change in the receptors.
This will lead to an exchange of GTP for GDP
Catalytic activation of adenylate cyclase - either stimulation or inhibition.
- Stimulation causes increased intracellular cAMP levels, activating pkA to phosphorylate target proteins (creb) to inititate biological responses.
73
What type of receptor does oxytocin and GnRH bind to?
It binds to Gq receptor.
74
Activating mutations of TSH receptor
Thyroid adenomas "constitutive ON"
75
Inactivating mutations of TSH receptor
resistance to TSH
76
What happens at a Gq receptors?
Stimulates phospholipase C. Converts PIP2 into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates the release of calcium from intracellular stores.
DAG activates PkC. These stimulate the phosphorylation of proteins and alter enzyme activity to initiate a biological response.
77
Loss of function mutations in GnRHR
Sex hormone deficiency and delayed puberty (hypogonadotrophic hypogonadism)
78
What are cytoplasmic/nuclear receptors? Examples of hormones that bind to them
They are intracellular. Steroid and thyroid hormones can diffuse across the plasma membrane of target cells and bind to the intracellular receptors. Cortisol is an example - binds to a nuclear receptor and translocates inside the nucleus binding to DNA to increase gene expression, inducing protein synthesis
79
What is important about cytoplasmic/nuclear receptors?
They function as hormone-regulating transcription factors, controlling gene expression. Nuclear receptors commonly share a transcriptional activation domain, a Zn2+ finger DNA binding domain and a ligand binding domain.
80
Pituitary adenoma
- When regulation goes wrong, either hypo or hyperthyroidism occurs
81
Hypothyroidism
- Too little thyroid hormone
| - If untreated, causes mental retardation, slow growth, cold hands and feet, lack of energy.
82
Common cause of hypothyroidism
Hashimoto's disease
- An autoimmune disease where the immune system makes antibodies to the thyroid.
- Worse in women and those with a family history of it
- Older people may occur following radioactive iodine treatment, thyroid surgery.
- Babies may be stillborn, or premature with lower IQ later in life
83
Hyperthyroidism or Graves' disease
- Induces anxiety
- An autoimmune disease where antibodies attach the thyroid gland and mimic TSH.
- Too much thyroid hormone.
- Occurs in women
84
Signs and symptoms of Graves' disease
- Enlarged thyroid gland
- Difficulty breathing, anxiety, irritability, difficulty sleeping
- Fatigue, rapid or irregular heartbeat, trembling fingers
85
Complications of Graves' disease
- Heart failure
| - Osteoporosis
86
Addison's disease
Adrenal insufficiency
- Occurs when the adrenals do not secrete enough steroids
- Most common cause is autoimmune
- Symptoms are fatigue, muscle weakness, weight loss, darkened skin on the face, neck and back of hands
87
Cushing's syndrome
- Excess cortisol secretion
- Exogenous factors such as patients taking cortisol-like mechanisms for treatment of other disorders
- Secondary feature - a sympton of something
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Cushing's disease
- Primary
| - Caused by pituitary tumours where too much ACTH is produced
89
Symptoms of Cushing's
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Weight gain
Rounded face
Extra fat on the upper back and above the clavicle
Diabetes
Hypertension
Osteoporosis
Muscle loss and weakness
Facial hair in women
Irregular menstruation
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