Lecture 16: Importance of Thyroid and Adrenal Hormones Flashcards
What is unique about thyroid hormones?
-Almost all cells have receptors except brain and heart
What is the thyroid gland?
-Located on both sides of the trachea, below the larynx
-2 lobes bridged by isthmus (a narrow passage ie trachea/esophagus)
-Heavily vascularized, it is the heaviest of pure endocrine glands (right by carotid)
-Composed of numerous follicles:
-Single layer of epithelial cells that release thyroid hormones
-Lumen filled with protein rich fluid (colloid)
-Between follicles, parafollicular cells (C-cells) secrete calcitonin
What is the synthesis of thyroid hormones?
- active uptake of iodine
-Iodine circulates I blood as iodide
-Actively transported through follicular cells (I/Na symport)
-Diffuses and accumulates in colloid as iodine (I2) - Iodination of thyroglobin (Tgb):
-Tgb, a glycoprotein with over 120 tyrosine residues, is released in the lumen
-Tyrosine peroxidase (TPO) binds I2 to tyrosine residues
-In colloid 10% of Tgb is iodinated
-Each tyrosine residue can be iodinated on possibly 2 sites: - I2 tyrosine= momoidodotyrosine
- I2 tyrosine= diiodotyrosine
- Tgb- I2 up-taken by endocytosis from colloid into cells, fused to lysosomes and split into third hormones
What happens after cleavage in follicular cell?
-When 2 diiodothyrosines are cleaved = tetraiodothronine or thyroxine (T4)
- 1 moniodityrosine + 1 diiodotyrosine = Triiodothyronine (T3)
-T3 and T4 represent 10 and 90% of thyroid hormones, respectively
-Lipophilic hormones –> diffuse across basal membrane into interstitial space then into blood capillaries
-In blood, binds to plasma proteins (carriers, TBG)
What is the difference between T3 and T4?
T4: inactive form, majority synthesized, need to be donated to become T3
T3: active form only about 10% of thyroid hormones, converted to T3 from T4 when the body needs it
What is the transport of thyroid hormone?
-TBG (thyroid binding globin) binds 70-80% of circulating thyroid hormones
-Remaining bound to other albumins
-Only 0.03% of T3 and T4 are free in blood and diffuse to tissues (only free hormone is active) thus there is several days of hormone available bound to TBG (small amount able to enter cell that is not bound to a carrier)
What are the actions of thyroid hormones?
-Main action os to increase basal metabolic rate by consuming O2 and glucose by:
-After diffusing in target cells, T4 is deiodinated to T3 (active form), binds to its nuclear receptor and actives gene transcription
-Affinity of receptor is higher for T3 than T4 (T4 5x more active)
-Thyroid hormones act on all cells of the body to increase basal metabolic rate, which will increase heat production and O2 consumption
-Areas where this doesn’t occur is the brain (doesn’t have storage), gonads (need specific temp for testes) and spleen
-During development thyroid hormones stimulate secretion of GH which is important for bone growth and tissue growth
-During the last phase of fetal development and early stage after birth, torpid hormones are caritas for normal maturation of brain function (lack of TH leads to cognitive problems)
-Thyroid hormones increase the number of adrenalin/noradrenalin receptors which boost sensitivity to Sympathetic system (reason why issues with hyperthyroid will cause a jumpy reaction in cats)
-Essential for gonadal normal function (lack results in reduced sperm production, irregular cycle)
-Increase nerve conduction velocity (faster reflexes)
Important piece* lots of receptors that are important for different results and almost all have TH receptors except a couple organs. The most important ones above are the BMR and the SNS effected by stress and enhances sensitivity)
How are Thyroid hormones metabolized?
-Deionization to reverse T3 in target tissues results deactivation
-After deactivation, diffuses out of target cell and is degraded in the liver (main organ for detoxification and deionization)
-The I2 release during metabolism can be recycled to the thyroid
How is TH regulated?
-TRH from HYPOTHAL increases TSH secretion form the ANTERIOR P
-TSH binds to its G-coupled receptor on membrane of follicular cells, stimulates cAMP pathway which in turn stimulates the endocytosis (bringing in more) of Tgb-I2 and the synthesis of TH (we can only control the synthesis)
-TH exert a negative feedback on both the pituitary and hypothalamus
-Exposure to cold for long period increase TRH release (bc BMR will create internal heat)
-If metabolites decrease (fasting) rapid decrease in TH (T3 and T4)
What are some thyroid pathologies?
-Hypothyroidism
-Goiter
-Hyperthyroidism
What is hypothyroidism?
3 different ‘types/causes’:
1. Primary hypothyroidism= In dogs most cases results from autoimmune disorder that destroy follicular cells (follicular cells destroyed)
2. Secondary hypothyroidism= low secretion of TSH, mainly due to injury to pituitary or hypothalamus (thyroid is fine but issue higher up chain with TSH or hypo)
3. Third hypothyroidism: Iodine deficiency
Most cell types affected by hypothyroidism:
-Reduced heat production and tolerance to cold
-Sluggish animal not feeding BUT gaining weight
-Impaired reproduction, constipation
Treatment: Thyroxine for the rest of life
What is Goiter?
-Enlarged thyroid gland
Several causes:
-Deficiency in iodine
-Tumor
-Inflammation
What happens: Lack of thyroid hormones increase TRH and TSH (problem with new feedback bc not hormones) stimulating multiplication (hyperplasia) and volume (hypertrophy) of follicular cells
-In costal areas good source of iodine, inland goitre more frequent in animals
What is hyperthyroidism?
-Over production of thyroid hormones
-Frequent in cats cause unknown
-Many target organs
Symptoms:
-Big appetites associated with weight loss (very skinny), excitable and nervous (increase response to catecholamines ie SNS), increase heart rate, increase respiration, increase digestive passage
Treatment: Surgery, radioactive I2 to destroy follicular cells
What is the structure of the adrenal gland?
adrenals= paired organs capping the kidneys
Consists of 2 layers:
-outer cortex: makes up 90% of the adrenal glands mass and has 3 layers
-inner medulla: part of the ANS (equivalent to a ganglion, but with post ganglion cells secreting catecholamines ie epinephrine/norepinepherine) that diffuse in the blood
What are the 3 areas of the cortex on the adrenal gland?
Cortex is composed of 3 layers:
1. Zona glomerulosa: outer most layer= secretes mineralcorticoids
2. Zona fasciculata: middle layer= secretes glucocorticoids
3.Zona reticularis: inner most layer= secretes androgens