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Neurophysiology > Neurohormones > Flashcards

Neurohormones Flashcards

1
Q

What is a neurohormone?

A

Hormone produced and released by neuroendocrine/neurosecretory nerve cell into the blood

  • circulated in blood and diffuse out of capillaries to act on complementary receptors
  • could potentially have widespread effect around body
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2
Q

What is the Speed of neurohormone communication?

A

slow as it takes time to release the hormone into the blood, circulate around the body, diffuse out of capillaries and activate the receptor

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3
Q

What is the Speed of neurone communication?

A

fast, however restricted as it only activates the neighbouring neurone and doesn’t have widespread effects

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4
Q

What are the Main control systems of the body?

A

Endocrine System

  • long lasting effects
  • slow communication

Nervous System

  • short lasting effects
  • fast communication
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5
Q

What are the different Types of Hormones?

A

Protein & Peptide Hormones

Amino Acid Derivatives

Steroid Hormones

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6
Q

Describe the structure of Protein/Peptide hormones.

A

> 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)

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7
Q

What are Amino acid derivatives?

A

> mostly tyrosine derived
neurotransmitter that can also act as a hormone
e.g. adrenaline, noradrenaline, dopamine

*serotonin (tryptophan derived)

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8
Q

What are Steroid Hormones?

A 
>steroid is a class of lipid derived from cholesterol
>e.g. cortisol, aldosterone, testosterone, progesterone, oestradiol
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9
Q

What is the Hypophyseal Portal System?

A

system of blood vessels that connects hypothalamus to anterior pituitary

Neurones project and release neurohormones directly into the portal system in the hypothalamus, and they are transported along the portal system to the anterior pituitary, where they act on receptors to release other neurohormones into the blood circulation. These neurohormones are circulated around the body and activate complementary receptors, having a widespread effect all around the body.

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10
Q

Which neurones project from the hypothalamus to the posterior pituitary?

A

magnocellular neurones

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11
Q

What is the Function of magnocellular neurones?

A

project from hypothalamus to posterior pituitary, releasing neurohormones (peptides- oxytocin & vasopressin) into the capillary network in posterior pituitary to be circulated around the body and activate complementary receptors

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12
Q

How are neurohormones released into the blood?

A

most follow a rhythmic pattern (not constant):

· Circadian Rhythms: based on a 24-hour cycle

Ø E.g. secretion of cortisol, GH, PRL

· Pulsatile (Ultradian) Rhythms: periodicity of less than 24 hours (usually every ½-2 hour)

Ø E.g. secretion of gonadotrophins in adults

· Infradian Rhythms: periodicity longer than 24 hours

Ø E.g. menstrual cycle

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13
Q

What are the key nuclei of neurosecretory cells in the brain?

A

Medial pre-optic nucleus
Arcuate nucleus
Paraventricular nucleus

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14
Q

How do hypothalamic neurohormones control the anterior pituitary?

A

Neurosecretory cells in the hypothalamus produce “releasing” and “release-inhibiting hormones” into the primary capillary plexus which are transported to the secondary capillary plexus to act on anterior pituitary receptors and induce the release of other hormones.

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15
Q

What are the Specialised cells in anterior pituitary responding to hypothalamic hormones?

A

· Corticotroph cells that control ACTH secretion in response to CRH

· Thyrotroph cells that regulate TSH secretion in response to TRH

· Gonadotroph cells that secrete LH and FSH in response to GnRH

· Somatotroph cells that control GH secretion in response to GHRH

· Lactotroph cells that control the secretion of prolactin in response to TRH, somatostatin and dopamine

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16
Q

What are the Hormones released by anterior pituitary and their respective functions?

A

FSH and LH
>Act on gonads

Growth Hormone (GH)
>Activates receptors in muscle and bone

Prolactin
>Stimulates mammary glands for milk production

ACTH
>Stimulates cortisol production in adrenal cortex

Thyroid Stimulating Hormone
>Binds TSH receptors in thyroid to produce thyroxine

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17
Q

What are the Hormones released by posterior pituitary and their respective functions?

A

Oxytocin (posterior pituitary)
>Stimulates mammary glands for milk production
>Induces smooth muscle contractions

Vasopressin (ADH) (posterior pituitary)
>Acts on kidney tubules to retain water

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18
Q

What is ACTH and what is it derived from?

A

39 amino acid peptide derived from a large precursor glycoprotein called proopiomelanocortin (POMC)

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19
Q

What is the Function of ACTH?

A

stimulates production of glucocorticoid (cortisol) and sex hormones from the zona fasciculate of the adrenal cortex

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20
Q

What are the Steps of Cortisol Synthesis?

A

1) Stress activates the hypothalamic-pituitary axis (HPA) by activating the hypothalamus to releasing CRH
2) CRH activates corticotroph receptors in anterior pituitary to release ACTH.
3) ACTH is released into the blood circulation and acts on ACTH receptors in the adrenal cortex to release cortisol.
4) Cortisol is then released into the blood circulation. Cortisol is important because it mobilises energy.

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21
Q

How do cortisol levels decrease?

A

via a negative feedback mechanism
-high cortisol detected by cortisol receptors in hypothalamus and pituitary, inhibiting the release of CRH from hypothalamus or ACTH from pituitary

22
Q

What does chronic stress cause?

A

hyper-stimulation of HPA axis, meaning increase in cortisol production, leading to high basal cortisol levels which eventually cause:

  • depression
  • anxiety related disorders
23
Q

Describe the Rhythm of Cortisol Secretion.

A

Circadian rhythm
-cortisol highest in the morning and decline during the day, reflecting the pattern of ACTH secretion from the anterior pituitary

*pattern of cortisol secretion probably reflects the body’s response to low blood glucose after overnight fasting

24
Q

What stimulates the production of TSH?

A

Thyrotropin releasing hormone (TRH) from the hypothalamus

25
Q

What is the Function of TSH?

A

stimulates thyroid gland to increase thyroxine (T4/3) secretion

26
Q

What is the most potent thyroid hormone?

A

T3 is the most potent thyroid hormone and targets tissues containing a deiodinase enzyme (DI) to convert T4 to T3

Pituitary also expresses deiodinase enzyme (DI) to convert T4 to T3

27
Q

How do thyroxine levels decrease?

A

via negative feedback mechanism:
-high thyroxine detected by thyroxine receptors on hypothalamus and pituitary, inhibiting release of TRH from hypothalamus and TSH from pituitary

28
Q

What is the effect of High thyroxine levels?

A

increased basal metabolic rate
tachycardia
anxiety (HPA important in behaviour)

29
Q

What is the effect of Low thyroxine levels?

A

weight gain
low energy
cognitive impairments/cretinism
depression

30
Q

What is prolactin?

A

199 amino acid protein with 3 disulphide bonds, released by lactotrophs in anterior pituitary

31
Q

What is the Function of prolactin?

A

Stimulates mammary gland development during puberty to produce milk

Maintains lactation (synergised by glucocorticoids, inhibited by oestrogen and progesterone- decrease of both after parturition)

32
Q

Describe the process of Prolactin regulation.

A
  • inhibited by dopamine.

- stimulated by thyrotropin releasing hormone (TRH) from hypothalamus

33
Q

What are oxytocin and vasopressin synthesised by and where?

A

Synthesised by magnocellular neurones in the supra-optic and paraventricular nuclei in the hypothalamus

then transported to the terminals of the nerve fibres located in the posterior pituitary

34
Q

What stimulates vasopressin release?

A

changes in the activity of the osmoreceptor complex in hypothalamus caused by:

  • dehydration
  • low blood pressure
35
Q

What are the Steps of Vasopressin Secretion?

A

Under these conditions (dehydration and low blood pressure):

1) Kidney releases an important enzyme known as renin
2) Renin cleavages an important molecule found in the liver called angiotensinogen into angiotensin I
3) Angiotensin I is converted to angiotensin II
4) Angiotensin II constricts blood vessels to increase blood pressure
5) Angiotensin II acts on the Subfornical organ in the brain, which signals for the release of vasopressin from the pituitary
6) Once vasopressin is released from the pituitary it induces thirst and also acts on kidneys to retain water in the distal tubules, increasing blood pressure.
7) Vasopressin also increases blood pressure by causing vasoconstriction

36
Q

What is the Function of Vasopressin (ADH)?

A

· Controls plasma osmolality by regulating water excretion and drinking behaviour (responds to thirst)
· Stimulates vascular smooth muscle contraction in the distal tubules of the kidney to reduce loss of water and raise blood pressure (water retention)
·Also has a vasoconstriction effect, raising blood pressure

37
Q

What stimulates oxytocin release?

A

Peripheral stimuli of cervical stretch receptors and suckling at breast for milk.

Also stroking, caressing, grooming

38
Q

What is the Function of oxytocin?

A

· Regulates contraction of smooth muscles (e.g. uterus during labour, myoepithelial cells lining the mammary duct, contraction of reproductive tract during sperm ejaculation)

39
Q

Describe the Levels of oxytocin.

A

usually undetectable, but elevated during parturition, lactation and mating

40
Q

Describe the process of Oxytocin Release During Labour.

A

During labour:

1) Baby is pushing against the uterus, and the uterus stretches, stimulating neurones
2) Neurones send a signal to magnocellular neurones to start releasing oxytocin
3) Oxytocin is released into the blood circulation and will act on oxytocin receptors in the uterus to cause uterine smooth muscle contractions
4) Baby is pushed forwards, causing more stretching, and causing for more oxytocin release via a positive feedback mechanism
5) This stops when the baby is delivered as there is no more stretching of the uterus

41
Q

What are the Social effects of oxytocin (peptide of love)?

A

There are also oxytocinergic projections from hyopthalamus to other brain regions e.g. olfactory region, amygdala, nucleus accumbens and septum etc. which have no peripheral effects and only social effects

found in animals that monogamy is due to high oxytocin receptors located in reward centres, confirming that oxytocin is extremely important for paired bonding behaviour and is seen as a pro-social hormone

42
Q

Describe Oxytocin as a psychoactive drug.

A

because it is important as a pro-social hormone, it has potential to be used as a psychoactive drug in behavioural treatments

43
Q

Describe the structure of the Insulin & Growth Hormone Receptor.

A

> Bind to cell surface receptors leads to dimerization of the receptors, subsequently recruiting tyrosine kinases (e.g. JAK2 or MAPK) which phosphorylate target protein (e.g. STAT) to induce biological responses.

Mutations in the growth hormone receptor gene can result in defective hormone binding or reduced efficiency of receptor dimerization, causing growth hormone resistance (Laron syndrome).

44
Q

Describe the structure of the TSH and ACTH Receptors.

A

G-protein coupled receptor/adenylate cyclase pathway (Gi & Gs):
-stimulation of adenylate cyclases increases intracellular cAMP, that activate PKA which phosphorylate target proteins (e.g. CREB) to initiate specific gene expressions and biological responses

Activating mutations of TSH receptor cause thyroid adenomas (constitutive ON)
Inactivating mutations of TSH receptor cause resistance to TSH

45
Q

Describe the structure of the Oxytocin and GnRH receptor?

A

G-protein coupled receptor (Gq)

  • PhospholipaseC converted to PIP2
  • PIP2 converted to IP3 and DAG
  • IP3 stimulates Ca2+ release from intracellular stores (ER)
  • DAG activates PKC, whcih stimulates phosphorylation of protein and alters enzyme activities to initiate a biological response

*loss-of-function mutations in GnRH causes sex hormone deficiency and delayed puberty (hypogonadotrophic hyopgonadism)

46
Q

Describe the structure of the Steroid and Thyroid Hormone Receptor.

A

Cytoplasmic/Nuclear Receptors

  • diffuse across plasma membrane of target cells and bind to intracellular receptors in the cytoplasm or the nucleus
  • these receptors function as hormone-regulated transcription factors, controlling gene expression
  • nuclear receptors commonly share a transcriptional activation domain (AF1), a Zn2+ finger DNA binding domain and a ligand (hormone) binding/dimerization domain
47
Q

What are the Effects of pituitary adenoma?

A
  • Loss of visual field (pressure on optic nerve)
  • Too much growth hormone, causing gigantism and acromegaly
  • Hypogonadism and infertility
  • Hypopituitarism (reduced pituitary function)
  • Too much ACTH secretion, causing excess cortisol secretion (Cushing’s syndrome)
  • Too much PRL (hyperprolactinaemia)
48
Q

What is Hypothyroidism (Hashimoto’s disease)?

A

Cause:

> Hashimoto’s disease, an autoimmune disease in which the immune system makes antibodies to the thyroid

> Seen more often in women and those with a family history of thyroid disease

Signs and Symptoms

> Induces decreased basal metabolic rate, increasing weight, bradycardia

> In terms of behaviour, induces cretinism, cognitive deficits, lethargy and depression

> In older people, it may follow radioactive iodine treatment, thyroid surgery or pituitary dysfunction

Complications

> goitre, heart failure, depression and slowed mental functioning, myxedema, birth defects

> Babies may be stillborn or premature with lower IQ later in life

> If left untreated, can cause mental retardation, slow growth, cold hands and feet, and lack of energy among other things

49
Q

What is Hyperthyroidism (Grave’s Disease)?

A

Cause

> Graves’ disease is an autoimmune disease where antibodies attack the thyroid gland and mimic TSH so the gland makes too much thyroid hormone

> Occurs in women (20-50; with a family history of thyroid disease)

Signs and Symptoms

> Goitre (enlarge 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

Complications

> heart failure, osteoporosis

> Pregnant women with uncontrolled Graves’ disease are at greater risk of miscarriage, premature birth, and babies with low birth weight

> If left untreated, causes Graves’ opthalmopathy (bulging eyes, relatively rare)

50
Q

What is Cushing’s Syndrome?

A

Cause

> Excess cortisol secretion

> Exogenous Cushing’s syndrome occurs in patients taking cortisol-like medications such as prednisone for the treatment of inflammatory disorders e.g. asthma and rheumatoid arthritis or after an organ transplant

> Cushing’s Disease is when pituitary tumour produces too much ACTH

Signs and Symptoms

> 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

> Huge increase in cortisol levels causes depression and anxiety-related disorders

51
Q

What is Addison’s Disease (Primary Adrenal Insufficiency)?

A

Cause

> Most common cause of primary adrenal insufficiency is autoimmune

Signs and Symptoms

> Fatigue, muscle weakness, decreased appetite, weight loss, nausea, vomiting, diarrhoea, muscle and joint pain, low blood pressure, dizziness, low blood glucose, sweating, darkened skin on the face, neck and back of the hands, irregular menstruation

Neurophysiology (10 decks)

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