The Thyroid Metabolic Hormones 2 major hormones

o Each thryoglobulin contains tyrosine

a.a.+ I2, to form the TH, w/c form w/in the thyroglobulin mol. and remain part of it even afterward as stored hormones in the follicular colloid o Each thyroglobulin mol. contains 1-3 T4 mol. and an ave. of 1 T3 mol. for every 14 mol. of T4. In this form, the TH are stored in the follicles the amt sufficient to supply the body for 2 to 3 months. When synthesis of thyroid hormone ceases, the effects of deficiency are not observed for several months o 93% of total thyroid hormone secreted is T4 and the remaining 7% is T3. However, almost all the T4 is eventually converted to T3 in the tissues, so that both are impt. functionally. In the next few days, most of the T4 is slowly deiodinated to form additional T3. Therefore the hormone finally delivered to and used by the tissues is mainly T3, a total of about 35 ug of T3 per day TRANSPORT OF T4 & T3 to TISSUES o

T4 or Thyroxine (90%) converted to

T3 when need arises - majority of T4 bound to plasma proteins - <1% of total TH will circulate in free form: T4 0.03% T3 0.3% (more potent) T4 thyrotoxicosis - T4; N T3 - T3 thryotoxicosis - T3; N T4 - T3 rises earlier than T4 Calcitonin hormone also secreted necessary for calcium metabolism TSH (thyroid Stimulating Hormone) secreted by AP w/c controls thyroid secretion -TRH TSH/thyrotropin TG to prod. T3 & T4

T3 or Triiodothyronine (10%)

o o o

proteins, transport proteins, and other substances) Impt types of Inc. Cellular metabolic activity Inc. in the basal metabolic activity of almost all tissues of the body. BMR can increase to 60 to 100% above normal when large quantities of the hormones are secreted. Inc. rate of food utilization needed for energy Inc. rate of protein synthesis w/ inc rate of protein catabolism also Inc. growth rate of young people, mental processes are excited, and activity of most of the endocrine glands is inc.

Decreases triglycerides, cholesterol, phospholipids Inc. free fatty acids o Decreased Thyroid Hormone

Inc triglycerides, cholesterol

phospholipids Excessive deposition of fat in liver Effect on Vitamin metabolism o A relative vitamin deficiency occurs when excess TH is secreted, unless at the same inc quantities of vitamins are available Effect on Basal Metabolic Rate: inc BMR Effect on Body Weight o Inc TH: decreased body wt. o Dec. TH : inc body wt. (these effects do not always occur because TH inc. the appetite and this may overbalance the change in metabolic rate) Effect on Cardiovascular System o Inc. tissue metabolism greater release of metabolic end products VASOLIDATATION inc. blood flow inc. cardiac output o Inc. excitability of the heart inc. heart rate o Inc enzymatic activity caused by inc. thyroid prod. Causes inc. strength of heartbeat o Inc. bld vol probably due in part to vasodilatation o Mean arterial pressure is unchanged

Hypothyroid: the rate of growth in

young children is retarded

Hyperthyroid: excessive skeletal

growth occurs, causing the child to become considerably taller at an earlier age . However, the bones mature more rapidly and the epiphyses close at an early age, so that the duration of growth and eventual height of the adult may actually be shortened. o Promote growth and development of the brain during fetal life and the first few years of postnatal life. If the fetus does not secrete enough quantities of TH, growth & maturation of the brain both before birth and afterwards are greatly retarded and the brain remains smaller than normal. This needs immediate thyroid therapy after birth or else the thyroid gland will remain deficient throughout life. EFFECTS of TH on SPECIFIC BODILY MECH - Organs unaffected by TH: *brain cells *retina *spleen *testes *lungs - Carbohydrate metabolism: o Enhanced glycolysis, gluconeogenesis, rate of GIT absorption, insulin secretion o Cause: overall inc. in cellular metabolic enzymes - Fat metabolism o Enhanced fat metabolism. Lipids are mobilized from fat tissues inc. free fatty acid conc. In plasma o Accelerates free fatty oxidation by cells - Effect on plasma and liver fat o Increased Thyroid Hormone

HypoTH TH, TSH (more

sensitive)

HyperTH TH, TSH Physiologic Significance complete lack of thyroid secretion basal metabolic rate falls to 40 to 50% below N extreme excesses of thyroid secretion BMR to rise to 60 to 100% above N FORMATION AND SECRETION of TH T4 and T3 are the same in quality but differ in rapidity and intensity T3 is 4x more potent than T4 but is present in the blood in smaller qty. and persist in shorter time than T4

Blood all except 1% of T4 & T3 combine immed. w/ several of the plasma proteins. T3 & T4 + thyroxine-binding globulin (TBG) combine with thyroxine-binding prealbumin & albumin T4 more strongly bound to plasma proteins thatn T3 o 70% globulin

o o -

20% prealbumin 10% albumin

o Inc. metabolism leads to inc utilization of

O2 with formation of CO2. These effects activate all mechanisms that inc the rate and depth respiration o GIT: inc appetite and food intake; inc rate of secretion of digestive juices and GIT motility. Diarrhea often results. Lack of TH causes constipation o CNS: inc rapidity of cerebration in general. Hyperthyroidism leads to extreme nervousness and psychoneurotic tendencies, such as anxiety complexes, extreme worry and paranoia o Skeletal: mild inc in TH makes muscle react w/ vigor; excessive levels muscle weakness due to excess protein catabolism

Diet (1 mg iodide/week) absorbed in GIT then into the blood most secreted by the kidney while 5% is selectively removed by cells of the thyroid gland and used for TH synthesis Iodide from diet peroxidase-> I2 + Tyrosine (Organification of thryoglobulin) 1) Monoiodotyrosine 2) Diiodotryosine

Mono + Diiodo = T3

Diiodo + Diiodo= T4

Iodide forms T3 & T4 & converts T4 to T3 (conc of iodide in the thyroid cell- 30x higher than blood level is called iodide trapping) Production of T4 and T3 in thyroid o Thyroglobulin- large glycoCHON secreted by ER and Golgi apparatus secrete into thyroid follicles

Slow release of T4 to the tissues. This is due to the high affinity of the plasmabinding CHONS for TH Half of the T4 in blood is released every 6 days Half of the T3 is released to the cells in 1 day T4 & T3 in tissue cells bind with intracellular proteins, with T4 binding more strongly than T3. Therefore they are again stored, but this time in the functional cells themselves, and they are used, slowly over a period of days or weeks GENERAL EFFECTS OF TH on TISSUES TH increase the transcription of large number of genes. The net result is a generalize increase in the functional activity throughout the body. (increase number of protein enzymes, structural

Most char. Of hyperthyroidism is fine

muscle tremor.

o Sleep: because of the exhausting effect of

TH on musculature & CNS, the hyperthyroid has a constant feeling of

tiredness, and because of excitable effects of the hormone on the synapses, it is difficult to sleep. Extreme somnolence is characteristic of hypothyroidism. o Sexual Func. Normal hormone: normal sexual func Lack of hormone: lack of libido in men and menorrhagia(excess menstruation) and polymenorrhea in women (excessive and frequent) Great excess: causes impotence in men and oligomenorrhea (reduced bleeding) to even amenorrhea in women. * amenorrhea - / TH Cause: direct metabolic effects on the gonads and excitatory and inhibitory feedback effects working thru the anterior pituitary hormones that control sexual func.