Neurohormones Flashcards

Question

Where are oxytocin and vasopressin synthesised and transported?

Answer 1

* 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

Answer 2

* 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

Answer 3

> 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

Answer 4

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)

Answer 5

* Hypnotic * Antidepressant * Antipsychotic * Social cognition * Induces trust * anti-OCD * Treatment of Autism * Anxiolytic

Answer 6

> 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’

Answer 7

• 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

Answer 8

• 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)

Answer 9

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

Answer 10

* 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

Answer 11

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)

Answer 12

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.

Answer 13

* 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