Neurohormones Flashcards
1
Q
What are neurohormones?
A
Neurohormones are neurotransmitters, released from brain neurons directly into the bloodstream
2
Q
How do neurohormones produce their effect?
A
Neurohormones circulate in the bloodstream and diffuse out of capillaries and act on their receptors to produce an effect
3
Q
How does neurohormone release directly into the blood stream affect their effects?
A
Point to point communication
- Fast, restricted
Neurons of secretory hypothalamus
- slow but widespread effect throughout body
Networks of interconnected neurons Autonomic Nervous System
- fast, widespread influence
Diffuse modulatory systems
- slower, widespread
4
Q
What are the 2 main control systems of the body?
A
- Endocrine system
- Nervous system
5
Q
Describe the endocrine system
A
Endocrine System
- Mediators travel within blood vessels
- Utilises chemical mediators (hormones)
- Slow communication
- Effects can be long-lasting
6
Q
Describe the nervous system and its effects
A
Nervous System
- Signalling along nerve fibres
- Transmission of electrical impulses
- Fast communication
- Effects are generally short-acting
7
Q
How are neurohormones produced?
A
Neurohormones are produced by specialised nerve cells called neurosecretory cells and released into the blood
8
Q
What is the significance of neurohormones?
A
Because they are defined as hormones, they are secreted into the blood and have their effect on cells some distance away, but the same compounds can also act as neurotransmitters or as autocrine (self) or paracrine (local) messengers.
=> endocrine and nervous system
A number of these peptides act as both hormones and neurotransmitters
Sometimes the endocrine and neural functions are linked in others they are not
9
Q
What are the principal endocrine organs of the body?
A
- Hypothalamus
- Pituitary gland
- Thyroid gland
- Parathyroid glands
- Adrenal gland
- Pancreas
- Ovary (F)
- Testes (M)
10
Q
What hormones are released from the Hypothalamus?
A
- TRH (thyrotrophin-releasing hormone)
- GnRH (Gonadotrophin-releasing hormone)
- CRH (Corticotrophin-releasing hormone)
- GHRH (Growth hormone releasing hormone)
- Prolactin-inhibiting factor (Dopamine)
- Somatostatin
11
Q
Which hormones are released from the anterior pituitary?
A
Anterior pituitary:
- TSH (thyroid stimulating hormone)
- LH (Luteinising hormone)
- FSH (Foliicle stimulating hormone)
- Growth hormone
- PL (prolactin)
- ACTH (adrenocorticotrophin)
12
Q
Which hormones does the posterior pituitary release?
A
The 2 important neurohormones released via the posterior pituitary are:
- Vasopressin (ADH)
- Oxytocin
13
Q
Which hormones are secreted from the adrenal cortex of the adrenal gland?
A
- aldosterone
- cortisol
14
Q
Which hormones are released form the adrenal medulla of the adrenal gland?
A
- epinephrine (adrenaline)
- norepeinephrine (noradrenaline)
15
Q
Which hormones are released from the pancreas?
A
Insulin, Glucagon and somatostatin
16
Q
Which hormones are released from the gonads?
A
Ovaries:
- Oestrogens, progesterones
Testes:
- Testosterone
17
Q
What are the different types of hormones?
A
- Protein and peptide hormones
- Amino acid derivatives
- Steroid hormones
18
Q
Outline the features of peptide and protein hormones
A
Protein & Peptide Hormones
- Vary considerably in size
- Can be synthesised as a large 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)
19
Q
Describe the features of amino acid derived hormones
A
Amino Acid Derivatives
- Mostly tyrosine derived
- Neurotransmitter that can also act as a hormone
E.g. epinephrine, norepinephrine, dopamine
20
Q
What are steroid hormones?
A
Steroid is a class of lipids derived from cholesterol
Include cortisol, aldosterone, testosterone, progesterone, oestradiol
21
Q
Where are neurohormones functionally required?
A
Neuropeptides (neurohormones) are functionally important transmitters in the Hypothalamo-pituitary axis
22
Q
What are the 2 components of the HPA axis?
A
The HPA has 2 components (anterior and posterior pituitary)
23
Q
How is the anterior pituitary connected to the hypothalamus?
A
Hypothalamus contains a network of blood vessels
The hypophyseal portal circulation connects to the adenohypophysis portal circulation in the anterior pituitary
⇒ project and release neurohormones into the portal capillary system, which activate their specific receptors, to induce further neurohormone release
24
Q
How does the hypothalamus connect to the posterior pituitary?
A
The posterior pituitary is connected to the hypothalamus via magnocellular neurons
25
Describe the release of GnRH from the hypothalamus to the anterior pituitary
GnRH is released from the hypothalamus into the anterior pituitary, via the portal system to activate release of FSH and LH → acts on gonads
GHRH is also released directly into the capillary system to stimulate release of growth hormone
26
How is CRH released to the anterior pituitary?
CRH is a peptide released directly into the portal system and acts on the anterior pituitary to release ACTH. ACTH stimulates cortisol release from the adrenal cortex
27
Describe the release of TRH from the hypothalmus
TRH released into portal circulation from hypothalamus onto the anterior pituitary to induce TSH release which acts on thyroid to stimulate thyroxine release
28
How are the posterior pituitary hormones released?
In the posterior pituitary, activated magnocellular neurons cause the release of 2 neurohormones (ADH, oxytocin)
29
Describe the effects of the posterior pituitary hormones
ADH acts on the kidneys, producing an antidiuretic effect and water retention
Oxytocin acts on the uterus to induce uterine contractions or on the mammary glands induces milk ejection
30
Describe the endocrine rhythms
Most, if not all, bodily activities show periodic rhythms or cyclic changes
Many of the hormones show periodicity
31
What are circadian rhythms?
Circadian Rhythms: based on a 24-hour cycle
| E.g. secretion of cortisol, GH, PRL
32
What are ultradian rhythms
Pulsatile (ultradian rhythms): periodicity of less 24 hours (usually every ½ - 2 hours)
33
What are infradian rhythms?
Infradian Rhythms: periodicity longer than 24 hours
| E.g. menstrual cycle
34
What is the significance of endocrine rhythms when sampling blood?
When sampling blood concentration of a hormone, you must consider the variability of hormone levels caused by the periodicity
35
Where is the pituitary located?
Pituitary lies in a bony cavity (sella turcica / pituitary fossa) in the sphenoid bone. The pituitary is connected to the hypothalamus by a stalk.
36
Where are hormones secreted from the hypothalamus towards the pituitary?
The hypothalamic hormones are secreted into the portal vein system at the median eminence
37
What is the significance of the pituitary stalk?
The delivery of these hormones is dependent on an intact pituitary stalk (infundibulum)
Any damage of the pituitary stalk will result in failure of gonadal, thyroid and adrenal function as well as misregulation of growth
38
Which hormones control the anterior pituitary?
The anterior pituitary contains specialised cells responding to these hypothalamic hormones:
Gonadotroph cells that secrete LH and FSH in response to GnRH
Somatotrophs that control GH secretion in response to GHRH
Corticotrophs that control ACTH secretion in response to CRH
Lactotrophs that control the secretion of prolactin in response to TRH, somatostatin & dopamine
39
Outline the hypothalamic neurohormones that stimulate hormone release in the anterior pituitary
Corticotropin Releasing Hormone (CRH): 41 amino acid peptide that controls the release of adrenocorticotropin (ACTH)
```
Thyrotropin Releasing Hormone (TRH): 3 a.a peptide, controls release of thyroid stimulating hormone (TSH)
and prolactin (PRL)
```
Gonadotropin Releasing hormone (GRH): 10 a.a peptide, controls release of luteinizing hormone (LH) and
follicle-stimulating hormone (FSH)
Growth Hormone Releasing Hormone (GHRH); 44 a.a peptide controls the release of growth hormone (GH)
Dopamine is a monoamine that inhibits PRL release
40
What is ACTH?
ACTH is a 39 amino acid peptide with a molecular weight of 4.5kDa
Belongs to a family of related peptide hormones derived from a large precursor glycoprotein, pro-opiomelanocortin (POMC)
41
What is the role of CRH?
Hypothalamic neurones release corticotropin releasing hormone (CRH) to stimulate pituitary corticotrophs to release ACTH into the circulation
42
What is the function of ACTH?
ACTH stimulates the production of glucosorticoid and sex hormones from the zona fasciculata of adrenal cortex
43
What is cortisol?
cortisol is a steroid hormone, more specifically a glucocorticoid.
Hydrocortisone is a name for cortisol used as medication
44
Describe glucocorticoid secretion in the body
Following changes in brain activity, plasma cortisol levels are highest first thing in the morning and decline during the day (reflecting the pattern of ACTH secretion by the anterior pituitary).
45
What should you consider about the circadian rhythm of glucocorticoid release when administering medication?
This circadian rhythm must be taken into account when considering cortisol replacement therapy as a clinical treatment. The pattern of cortisol secretion probably reflects the body’s response to low blood glucose after overnight fasting.
46
What is the function of TSH?
TSH acts on the thyroid to increase T4/T3 secretion. T3 is the most potent thyroid hormone and target tissues contain a deiodinase enzyme (DI) to convert T4 to T3.
The pituitary also expresses deiodinase to convert T4
to T3 to facilitate negative feedback.
47
What is the structure and function of prolactin?
Human PRL is a 199 amino acid protein with a molecular weight of 22kDa & contains three disulfide bonds
Released by the lactotrophs in the anterior pituitary
```
Stimulates mammary gland development during puberty
Maintains lactation (synergised by glucocorticoids, inhibited by oestrogen and progesterone - decrease of both after parturition)
```
48
How is prolactin release regulated?
Its regulation is under dominant negative control of dopamine
Increased during pregnancy and lactation
49
Where are the posterior hormones produced?
Synthesised in the supraoptic and paraventricular nuclei in the hypothalamus
Transported to the terminals of the nerve fibres located in the posterior pituitary
Structurally quite similar, yet have very different functions
50
How is ADH release mediated?
Release stimulated by changes in the activity of the osmoreceptor complex in the hypothalamus
51
What is the role of ADH?
Controls plasma osmolality by regulating water excretion and drinking behaviour
Stimulates vascular smooth muscle contraction in the distal tubules of the kidney to reduce water loss and raise BP
52
Outline how ADH secretion is stimulated
1. Kidneys secrete renin when BV / BP is low
2. Renin converts Angiotensinogen → Angiotensin I →
Angiotensin II
3. Angiotensin II is detected by the subfornical organ
4. Subfornical organ projects to ADH cells & neurons in
lateral hypothalamus
5. Increased vasopressin (ADH) production and thirst
53
When is oxytocin released?
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
It may also be involved in responses to stroking, caressing, grooming
54
What is the function of oxytocin?
Oxytocin regulates contraction of smooth muscles (e.g. uterus during labour, myoepithelial cells lining the mammary duct, contraction of reproductive tract during sperm ejaculation)
55
Describe how positive feedback mediates oxytocin release during labour
During labour, the baby starts pushing the uterus causing stretching. The stretching stimulates neurons which send signals to the magnocellular neurons to release oxytocin
Oxytocin is released into circulation and acts on its oxytocin receptors in the uterus to cause uterine contractions, moving the baby forwards → causing more stretching and induces a positive feedback
Oxytocin release is ceased once the baby is out, as stretching stops
56
Where else in the body does oxytocin have a role?
There are oxytocinergic projections from the hypothalamus to other regions of the brain such as:
Olfactory region of the brain
Reward centres of the brain (nucleus accumbens)
Emotional centres of the brain (amygdala in the septum)
57
What are the CNS effects of oxytocin?
- Hypnotic
- Antidepressant
- Antipsychotic
- Social cognition
- Induces trust
- anti-OCD
- Treatment of Autism
- Anxiolytic
58
How do peptide and protein hormones produce their effects?
Peptide and protein hormones bind to surface receptors and active intracellular signalling mechanisms that result in alteration of target protein and/or enzyme activities
59
Outline the molecular mechanism of insulin and GH
Binding of insulin and GH to its cell surface receptors leads to dimerisation of the receptors, subsequently recruiting tyrosine kinases (e.g. JAK2 of MAPK) which phosphorylate target proteins (e.g. STAT) to induce biological responses
60
What is the consequence of GH receptor defects?
Mutations in the GH receptor gene can result in defective hormone binding or reduced efficiency of receptor dimerisation
→ GH resistance ‘Laron Syndrome’
61
Outline the GPCR / AC pathway
GPCRs are the largest of the cell surface receptor groups with over 140 members.
GPCR has 7 transmembrane domains
Hormone binding causes conformational changes in the receptor, leading to GTP exchange for GDP and catalytic activation of adenylate cyclase
62
Which hormones activate GPCRs and AC pathways?
TSH and ACTH bind to cell surface GPCRs and activate G-proteins that stimulate / inhibit adenylate cyclase
63
Outline the effects of AC stimulation
Stimulation of adenylate cyclase increases intracellular cAMP levels → activate protein kinase A → phosphorylates target proteins (e.g. CREB) to initiate specific gene expressions and biological responses
64
What are the effects of TSH receptor mutations?
- Activating mutations of TSH receptor → thyroid adenomas ‘constitutive ON’
- Inactivating mutations of TSH receptor → resistance to TSH
65
Which hormones activate the IP3/DAG pathway?
Oxytocin and GnRH bind to cell surface GPCRs and stimulate phospholipase C to convert phosphatidylinositol bisphosphate (PIP2) → inositol triphosphate (IP3) and DAG
66
Outline the effects of the IP3 pathway
IP3 stimulates Ca2+ release from intracellular stores (esp. In the ER)
DAG activates PKC
> these stimulate the phosphorylation of proteins and alter enzyme activities to initiate a biological response
67
What does a mutation in GnRHR cause?
Loss of function mutations in GnRHR
| → sex hormone deficiency and delayed puberty (hypogonadotrophic hypogandism)
68
Which hormones bind to cytoplasmic / nuclear receptors?
Steroid and thyroid hormones can diffuse across the plasma membrane of target cells and bind to intracellular receptors in the cytoplasm / nucleus
69
How do cytoplasmic /nuclear receptors function?
These receptors function as hormone-regulated transcription factors, controlling gene expression
70
Describe the structure of nuclear receptors
Nuclear receptors commonly share a transcriptional activation domain (AF1), a Zn2+ finger DNA binding domain and a ligand (hormone) binding / dimerisation domain
There are more than 150 members of receptor proteins, the majority of which are ‘orphan’ receptors
71
What is the consequence of pituitary adenoma?
If this regulation goes wrong, either hypo or hyperthyroidism occurs
72
What causes hypothyroidism?
Hypothyroidism occurs if there is too little thyroid hormone.
Affects 1 in 4000 infants.
If left untreated, can cause mental retardation, slow growth, cold hands and feet, and lack of energy etc.
73
What is the most common cause of hypothyroidism?
Hashimoto’s disease: autoimmune disease in which the immune system makes antibodies to the thyroid.
More often in women and those with a family history of thyroid disease.
74
Why may older people present with Hashimoto's disease?
In older people it may follow radioactive iodine treatment, thyroid surgery or pituitary dysfunction; sometimes with goitre, heart failure, depression and slowed mental functioning, myxedema, birth defects.
75
What are the causes of hyperthyroidism?
Graves’ disease: autoimmune disease
Antibodies attack thyroid gland and mimic TSH => gland produces excess thyroid hormone (hyperthyroidism).
Often occurs in women (20 – 50; with a family history of thyroid disease).
76
What are the signs of hyperthyroidism?
Goitre (enlarged thyroid gland) ,Difficulty breathing, Anxiety, irritability,difficulty sleeping, fatigue, Rapid or irregular heartbeat, trembling fingers, Excess perspiration, heat sensitivity, Weight loss, despite normal food intake
77
What complications are associated with hyperthyroidism?
heart failure, osteoporosis. Pregnant women with uncontrolled Graves’ disease are at greater risk of miscarriage, premature birth, and babies with low birth weight.
Graves’ ophthalmopathy (occurs if untreated; bulging eyes, relatively rare)
78
What are the 2 aspects of adrenal pathology?
- Adrenal insufficiency (Addison’s disease)
| - Excessive secretion (Cushing’s syndrome)
79
What causes adrenal insufficiency?
Adrenal insufficiency (AI) occurs when the adrenals do not secrete enough steroids.
The most common cause of primary AI is autoimmune,
80
What are the symptoms of Addison's Disease?
Symptoms include fatigue, muscle weakness, decreased appetite, and weight loss, nausea, vomiting, and diarrhea, muscle and joint pain, low blood pressure, dizziness, low blood glucose, sweating, darkened skin on the face, neck, and back of the hands and irregular menstruation.
81
What causes Cushing's syndrome?
Results from having excess cortisol secretion
Exogenous Cushing’s syndrome occurs in patients Taking cortisol-like medications such as
Prednisone for the treatment of inflammatory disorders eg asthma and Rheumatoid arthritis or after organ transplant.
It can also occur with pituitary tumors produces too much ACTH (Cushing’s disease).
82
What are the symptoms of Cushing's syndrome?
Weight gain, rounded face and extra fat on the upper back and above the clavicles, diabetes, hypertension, osteoporosis, muscle loss and weakness, thin, fragile skin that bruises easily, purple-red
stretch marks, facial hair in women, irregular menstruation.
