Neurohormones Flashcards
What are neurohormones?
Neurohormones are neurotransmitters, released from brain neurons directly into the bloodstream Neurohormones circulate in the bloodstream and diffuse out of capillaries and act on their receptors to produce an effect.
Point to point to communication, neurones of secretory hypothalamus, network of interconnected neurones and diffuse modulatory systems
Describe the actions of these
A: Point to point communication
- Fast, restricted
B: Neurons of secretory hypothalamus
- slow but widespread effect throughout body
C: Networks of interconnected neurons Autonomic Nervous System
- fast, widespread influence
D: Diffuse modulatory systems
- slower, widespread
What are the 2 main control systems of the body?
> the body had 2 main control systems
• Endocrine system
• Nervous system
Describe the factors of the endocrine system
- Mediators travel within blood vessels
- Utilises chemical mediators (hormones)
- Slow communication
- Effects can be long-lasting
Describe the factors of the nervous system
- Signalling along nerve fibres
- Transmission of electrical impulses
- Fast communication
- Effects are generally short-acting
What are the principle endocrine organs of the body?
On image
What are the 3 types of hormones?
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)
Amino Acid Derivatives
• Mostly tyrosine derived
• Neurotransmitter that can also act as a hormone
• E.g. epinephrine, norepinephrine, dopamine
Steroid Hormones
• Steroid is a class of lipids derived from cholesterol
• Include cortisol, aldosterone, testosterone, progesterone, oestradiol
Where are neurohormones released from?
Neuropeptides (neurohormones) are functionally important transmitters in the Hypothalamus-pituitary axis
Describe the circulation of the hypothalamus and pituitary
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
What 2 hormones are released from the posterior pituitary gland?
- Vasopressin (ADH)
* Oxytocin
Describe the actions of TRH, ADH and oxytocin
- TRH released into portal circulation from hypothalamus onto the anterior pituitary to induce TSH release which acts on thyroid to stimulate thyroxine release
- In the posterior pituitary, activated magnocellular neurons cause the release of 2 neurohormones (ADH, oxytocin)
- 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
What are Circadian Rhythms?
Give some examples
Circadian Rhythms: based on a 24-hour cycle
E.g. secretion of cortisol, GH, PRL
What are Pulsatile (ultradian rhythms?
Give some examples
Pulsatile (ultradian rhythms): periodicity of less 24 hours (usually every ½ - 2 hours)
E.g. secretion of gonadotropins in adults
What are Infradian Rhythms?
Give some examples
Infradian Rhythms: periodicity longer than 24 hours
E.g. menstrual cycle
Describe the anatomy of the Hypothalamo-Hypophyseal System
Where does the pituitary gland lie?
Where are hormones released from in the hypothalamus?
- Pituitary lies in a bony cavity (sella turcica / pituitary fossa) in the sphenoid bone. The pituitary is connected to the hypothalamus by a stalk.
- The hypothalamic hormones are secreted into the portal vein system at the median eminence
- 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 mis regulation of growth
- A number of these peptides act as both hormones and neurotransmitters
- Sometimes the endocrine and neural functions are linked in others they are not
Describe the structure of Corticotropin Releasing Hormone (CRH)
41 amino acid peptide that controls the release of adrenocorticotropin (ACTH)
Describe the structure of Thyrotropin Releasing Hormone (TRH)
3 amino acid peptide that controls the release of thyroid stimulating hormone (TSH) and prolactin (PRL)
Describe the structure of GnRH
10 amino acid peptide that controls the release of luteinizing hormone (LH) and
follicle-stimulating hormone (FSH)
Describe the structure of Dopamine
A monoamine that inhibits the release of PRL
What specialised cells does the anterior pituitary contain and what do they secrete?
What do somatrophs release?
What do corticotrophs release
What does Lactotrophs release?
- 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
How big is the ACTH hormone?
What is it synthesised from?
What does ACTH release?
• 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)
• Hypothalamic neurones release corticotropin releasing hormone (CRH) to stimulate pituitary corticotrophs to release ACTH into the circulation
• ACTH stimulates the production of glucosorticoid and sex hormones from the zona fasciculata of adrenal cortex
cortisol is a steroid hormone, more specifically a glucocorticoid. Hydrocortisone is a name for cortisol used as medication
Describe the levels of cortisol throughout the day
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).
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.
How is TSH and thyroid hormone regulated?
- A good example of endocrine control is the regulation of TSH and thyroid secretion by negative feedback
- Thyrotrophic releasing hormone (TRH) from the hypothalamus stimulates the anterior pituitary 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 contain a deiodinase enzyme (DI) to convert T4 to T3.
- The pituitary also expresses deiodinase to convert T4
- to T3 to facilitate negative feedback.
Where is prolactin released from?
What does it stimuate?
What regulates it?
- 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)
- Its regulation is under dominant negative control of dopamine
- Increased during pregnancy and lactation
Where are oxytocin and vasopressin synthesised and transported?
- 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
What stimulates the release of vasopressin?
What does vasopressin control?
What does it stimulate?
- Release 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 water loss and raise BP
What 5 things occur when blood pressure and volume is low?
> communication between the brain and kidneys
When BV or BP is low, the kidneys secrete renin into the bloodstream.
Renin in the blood promotes angiotensin II synthesis which excites neurons in the subfornical organ
The subfornical neurons stimulate the hypothalamus, causing an increase in vasopressin (ADH) production and thirst
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
Describe the action of oxytocin
Where does oxytocin neurones project to in the brain?
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
Oxytocin regulates contraction of smooth muscles (e.g. uterus during labour, myoepithelial cells lining the mammary duct, contraction of reproductive tract during sperm ejaculation)
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
> oxytocin - hormone of love ; also released as a neuropeptide
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)
What are the CNS effects of oxytocin
- Hypnotic
- Antidepressant
- Antipsychotic
- Social cognition
- Induces trust
- anti-OCD
- Treatment of Autism
- Anxiolytic
What happens when protein and peptide hormones bind?
What happens when insulin binds?
> mechanism of action depends on the classes of hormones and their receptors
Peptide and protein hormones bind to surface receptors and active intracellular signalling mechanisms that result in alteration of target protein and/or enzyme activities
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
> mutations in the GH receptor gene can result in defective hormone binding or reduced efficiency of receptor dimerisation → GH resistance ‘Laron Syndrome’
Describe the GPCR pathway
How many transmembrane domains do they have?
What occurs when its activates
Give some examples of hormones that bind to GPCRs
What does an activating and inactivating mutation of the TSH receptor cause?
• 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
• TSH and ACTH bind to cell surface GPCRs and activate G-proteins that stimulate / inhibit adenylate cyclase
• 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
> activating mutations of TSH receptor → thyroid adenomas ‘constitutive ON’
> Inactivating mutations of TSH receptor → resistance to TSH
What happens when oxytocin and GnRH bind to receptors?
• Oxytocin and GnRH bind to cell surface GPCRs and stimulate phospholipase C to convert phosphatidylinositol bisphosphate (PIP2) → inositol triphosphate (IP3) and DAG
• 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
• Loss of function mutations in GnRHR
• → sex hormone deficiency and delayed puberty (hypogonadotrophic hypogandism)
Describe the action of cytoplasmic and nuclear receptors
Steroid and thyroid hormones can diffuse across the plasma membrane of target cells and bind to intracellular receptors in the cytoplasm / 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 / dimerisation domain
There are more than 150 members of receptor proteins, the majority of which are ‘orphan’ receptors
What is hypothyroidism?
What does it cause?
What is Hashimoto’s disease?
What problems does this cause?
- If this regulation goes wrong, either hypo or hyperthyroidism occurs
- Hypothyroidism occurs if there is too little thyroid hormone.
- This disease affects 1 in
- 4000 infants. If left untreated, it can cause mental retardation, slow growth, cold hands and feet, and lack of energy among other things.
- The most common cause is Hashimoto’s disease an autoimmune disease in which the immune system makes antibodies to the thyroid. It is seen more often in women and those with a family history of thyroid 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.
- Babies may be stillborn or premature with lower IQ in later in life.
- The brain mechanisms underlying these changes in function are not well understood
What does Hyperthyroidism - Grave’s Disease:
cause
signs and symptoms
complications
Cause:
• Graves’ disease is also an autoimmune disease
• Antibodies attack the thyroid gland and mimic
• TSH so the gland makes too much thyroid hormone (hyperthyroidism).
• It often occurs in women (20 – 50; with a family history of thyroid disease).
Signs and Symptoms:
• 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
Complications:
• 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)
What are the two types of adrenal pathology?
What is the cause of insufficney?
Once again there are 2 aspects of Adrenal pathology:
● Adrenal insufficiency (Addison’s disease)
● Excessive secretion (Cushing’s syndrome)
Adrenal insufficiency (AI) occurs when the adrenals do not secrete enough steroids.
Cause: The most common cause of primary AI is autoimmune,
Symptoms
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.
What is Cushing 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). Signs and symptoms of Cushing’s syndrome include: 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
