Module 8 Flashcards

Question

What are the interactions of TRs with DNA? | 3 pts

Answer 1

Thyroid hormone receptors bind to TRE on DNA **regardless of whether they are occupied by T3** * The biological effects of TRE binding by the unoccupied versus the occupied receptor are dramatically different * In general, binding of TR alone to DNA leads to **represssion of transcription**, wheas binding of the thyroid hormone-receptor complex **activates trancription**

Answer 2

Thyroid hormones generally **act permissively** * They cooperate with other hormones to exert physiological and behavioural effects * All cells in the body are targets for thyroid hormones!

Answer 3

1. Effects on metabolic pathways 2. Effects on cellular differentiation and development

Answer 4

Thyroid hormones stimulate diverse metabolic activities in most tissues, leading to an increase in basal metabolic rate * increase in O2 consumption and heat production by simulation of Na+, K+ ATPase (rate of ATP hydrolysis) = increase of body heat production * akin to blowing on a smoldering fire

Answer 5

1. Lipid metabolism * stimulate fat metabolization, leading to increased concentrations of fatty acids in plasma * enhance oxidation of fatty acids in many tissues * plasma concentrations of cholesterol and triglycerides are inversely correlated with thyroid hormone levels - one diagnostic indication of hypothyroidism is increased blood cholesterol concentration 2. Carbohydrate metabolism * stimulate almost all aspects of carbohydrate metabolism * enhancement of insulin-dependent entry of glucose into cells * increased gluconeogenesis and glycogenolysis to generate free glucose

Answer 6

1. Growth * necessary for normal growth in children and young animals (growth-retardation observed in thyroid deficiency) * growth -promoting effect of TH is intimately intertwined with that of GH (synegistic effect with GH and IGF-1 in target tissues) 2. Development * fetal Hyo-Pit-Thyroid axis functions at week 11 gestation in mammals * normal levels of TH are essential to brain development **(stimulates axonal growth and development)** * responsible for unique growth and differentiation in other vertebrates (metamorphosis)

Answer 7

1. Cardiovascular system * increase heart rate, cardiace contractility and cardiac output * promote vasodilation, which leads to enhanced blood flow to many organs 2. Central nervous system * decrease TH and the individual tends to feel mentally sluggish, while increase induces anxiety and nervousness 3. Reproductive system * reproductive behaviour and physiology is dependent on having essentially normal levels of TH * ypothyroidism in particular is commonly associated with infertility

Answer 8

1. alterations in the circulating levels of TH 2. impaired metabolism of TH in the periphery 3. resistance to TH actions at the tissue level

Answer 9

* Normal thyroid - euthyroid state: an individual whose thyroid function is normal * Inactive Thyroid * Hyperactive Thyroid

Answer 10

1. Insufficient synthesis of TH due to lack of iodine in the diet (1o hypothyroidism) * Fetal: hypothyroidism during early stages of development results in cretinism in humans (decreased mental capacity) * Adults: hypothyroidism in adults causes goiter (enlargement of the thyroid due to hypertrophy - excess TSH stimulation)

Answer 11

* retarded development + stunted growth * Mental retardation * puffy eyes, short jaw stature * altered timing of sexual maturation

Answer 12

* Lack of appetite, slow heart rate, dermatological disorders, redced fertility * First indication of iodine deficiency in a herd is goiter of newborn animals (mothers will oftern appear normal due to efficient uptake of iodine at expense of fetus)

Answer 13

2. Pituitary lesions on thyrotropes in AP - 2o hypothyroidism * results in decreased TSH release from anterior pituitary 3. Hypothalamic failure - 3o hypothyroidism 1o + 2o + 3o hypothyroidism all result in decrease T4 release from thyroid gland = hypofunction

Answer 14

* Very common cause of hypothyroidism (chronic, lymphocytic) * Autoimmune condition - immune system attacks normal follicles * Most common form of hypothyroidism in dogs * Hashimoto's Disease in humans (females 30-50 years) * Result of antibodies to TPO, TGB * Lab values - High TSH, Low T4 - Detection of TPOAb, TGBAb

Answer 15

Symptoms in animals due to decreased T4: * ↓ metabolic rate, O2 consumption = cold-intolerant, lethargy, obesity * ↓ protein synthesis = brittle nails, thinning hair, dry skin, slow bone growth in children/young animals, shorter stature * ↓ nervous system actions = slowed speech, reflexes and thought processes * ↓ cardiac output = slower heart rate, bradycardia

Answer 16

Diagnosis * Low T4, High TSH - 1 o à check for antibodies * Low T4, Low TSH - 2 o + 3 o à TRH stimulation test, imaging Treatment * Administration of synthetic T4: Synthroid * Treatment prevents bone loss, cardiomyopathy, myxedema

Answer 17

TSH receptors in thyroid gland attacked by thyroid stimulating immunoglobulins (TSI) - autoantibodies * causes the TSH receptors in the gland to be stimulated * autoimmune disease * ↑ TH production and release * clinical term = thyrotoxicosis (Graves Disease)

Answer 18

Symptoms due to** increased** T4 and T3: * ↑ metabolic rate, O2 consumption = warm-intolerant, warm + sweaty skin * ↑ protein catabolism and muscle weakness = weight loss * ↑ nervousness and excitability, sleeplessness (insomina), irritability * ↑ beta-adrenergic receptors in the heart = rapid heart beat and force of contraction * exophthalmos (bulging eyes): common symptom * diffuse goiter Diagnosis * Symptoms of hyperthyroidism * Low TSH, norm/high Free-T 4 , anti-TSH Ab (Graves Disease)

Answer 19

* Most common in middle-aged to old cats but also develops rarely in dogs * Cats: cause is thyroid adenoma (70%) * Dogs: thyroid carcinoma * Symptoms weight loss despite an increased appetite, nervousness, and tachycardia * Radioiodine therapy, thyroidectomy, chronic administration of an antithyroid drug, or lifelong nutritional therapy (iodine-deficient diet)

Answer 20

Goal of therapy is to decrease synthesis or release or activity of thyroid hormone by: 1. Removing all or part of thyroid gland * Surgical ablation: thyroidectomy * Radiation: ingesting radioactive iodine to cause destruction of tissue * Patients become hypothyroid and require exogenous thyroid hormone 2. Inhibiting the synthesis * Thioamide drugs: methimazole and propylthiouracil are main drugs * Methimazole is about 10X more potent with fewer adverse effects (liver damage) * Both drugs inhibit: * Iodination of tyrosines * Coupling of MIT and DIT to form T3 and T4 * PTU also inhibits deiodination in perhipheral tissues (less T3 formed from T4) 3. Blocking the release of THs * Pharmacologic dose of iodide prevent iodination as well as release of THs from thyroglobulin

Answer 21

* Metamorphosis: means change in form or transformation * Process in fishes and amphibians but is most pronounced in amphibians * Results in a changes in the ecological niche of the animal

Answer 22

* A major life stage transition in birds and other oviparous sauropsids is the hatching of the cleidoic egg * Transition from a relatively well-protected “aqueous” environment to a more hazardous and terrestrial life outside the egg à just like amphibians!!!

Answer 23

* in precocial birds, such as chickens and quail, the thyroid gland develops early in embryonic life * In altricial birds, thyroidal T4 content is very low throughout embryonic life, increases slightly during about the 1st week post-hatch * The peri-hatch period in precocial birds is characterized by peak values of blood THs * We don’t see this in altricial birds * Hatching is delayed or even inhibited when the circulating TH levels in precocial birds are experimentally prevented to rise, while altricial birds naturally hatch in the absence of high TH concentrations!

Module 8 Flashcards

(47 cards)