BICD 150 Sp 14 Fortes 4 4 22 14 1 of 8 Lecture 7 TRH is the smallest peptide hormone 3amino acids long Main effect is stimulation of thyrotrophs in ant pituitary Can also stimulate prolactin release in high concentrations TSH LH and FSH are all protein dimers with the same alpha subunit and different beta subunits TSH Receptor GPCR Both Gas and Gaq coupled will increase both Ca and cAMP in follicular cells Can be targeted by antibodies of the immune system Ab o TSH R Stimulating antibody binds to receptor and acts as if it is TSH seen Graves Disease hyperthyroidism o TSH R Blocking Ab Hashimoto s Thyroiditis hypothyroidism o TPO thyroid peroxidase Ab hypothyroidism o TGB thyroglobulin Ab hypothyroidism Effects of TSH Increased growth of thyroid cells including volume and vascularity cause the growth of a Goiter Increased Iodide uptake and transport Increase NIS and Pendrin transporter protein synthesis Page 1 of 8 Stimulate TPO synthesis and activity iodination and coupling of tyrosine Stimulate synthesis and secretion of TGB Stimulate pinocytosis of iodinated TGB back into the follicle from the colloid Increase number of lysosomes increase TGB digestion increase in T3 T4 release Thyroid receptors TR mainly bind T3 are in the nucleus and are inactive bound to corepressors not HSPs T3 T4 diffuses into cells and are transported into the nucleus T3 binds to TR T4 is converted into T3 before binding TR will dissociate from its co repressor and bind co activator TR complex will bind DNA and will affect transcription Physiological effects of thyroid hormones Essential for development of the fetus both growth and development of CNS o Deficiency of thyroid hormones in a developing baby will have permanent problems Cretinism o Cretinism Mental retardation lack of growth dwarfism o If identified early babies are now tested for TSH levels after birth babies can be supplemented to prevent the disease Metabolic effects o Increase metabolism o Increase O2 consumption o Increase heat generation biochemical reactions are exothermic and release heat o Increase Na K ATPase activity transporters located in all cells and are the main consumers of ATP and therefore O2 o Increase Ca ATPase activity o Increase Lipolysis o Increase of mitochondria Increase O2 consumption o T3 T4 can uncouple oxidative metabolism thyroid hormones were prescribed to lose weight bad idea Page 2 of 8 Cardiovascular effects o Increase fast myosin o Increase B1 adrenergic receptors which are Gas coupled increase hear rate and Contractility complaint of hyperthyroidism is heart palpitation increase HR Intestinal Effects o Increase motility particularly in the colon hyper defecation 2 or 3x a day in hyperthyroid Opposite in hypothyroid Hematopoietic effects o Increase red blood cell and hemoglobin production hypothyroid is often anemic o Increase growth of bone and Ca deposition o Increase resorption of bone bone turnover Muscular Effects o Pulmonary Effects o Increase in fast myosins hyperthyroid tend to have faster reflexes jitter or tremor Maintain ventilation hypothyroid tend to have hypoventilation Increased Sympathetic responses in general Lack of dietary iodine can cause hypothyroidism problem solved in the US by adding it to table salt Decreased T3 T4 synthesis increased TRH and TSH High TSH will stimulate growth of thyroid goiter can scavenge the blood for iodide more effectively and can even bring hormonal levels back to normal Hyperthyroid Either an excess of TRH TSH or excessive function of thyroid gland itself high T3 T4 Primary hyperthyroidism Thyroid gland overproduces T3 T4 Secondary hyperthyroidism Pituitary Gland overproduces TSH Hyperthyroidism Symptoms Weight loss Page 3 of 8 Heat intolerance Nervous increased reflexes tremors Tachycardia Hyper defecation Goiter Exophthalmos in the case of Graves disease antibody reacts with some antigens around the muscles behind the eyes causing them to bulge out of their sockets Treatment of hyperthyroidism Inhibit TPO with drugs Radioactive iodine to destroy the thyroid patients would have to be supplemented for life afterwards Hypothyroidism Hashimoto s Thyroiditis is the most common cause Constipation Weight gain Lethargy Page 4 of 8 BICD 150 Sp 14 Fortes 4 4 24 14 5 of 8 Lecture 8 Hypothyroidism Dry skin Weight gain rarely more than 50lbs Swelling Malaise No such thing as giving little bit of thyroid hormone as a treatment The dose you give will shut down endogenous the body s normal production via negative feedback Given dose needs to be large enough for them to live normally on for their lifetime Subclinical hypothyroidism Normal T4 levels but elevated TSH Sign of a failing thyroid gland Decision to treat may be difficult depends on severity of symptoms Estrogen or birth control pill can raise Thyroid binding globulin TBG levels Will look like levels of free T4 are low because more of it is bound to TBG Hyperthyroidism Graves disease most common Page 5 of 8 lose weight Sweaty Nervous Tired too active too much of the time Goiter Eye bulging Exophtalmus Treated by Anti thyroid drugs that decrease thyroid hormone made Radioactive iodine Goiters can be caused by either hyper or hypothyroidism Iodide deficiency can cause the growth of the thyroid as it scavenges the blood for iodide as discussed earlier Overstimulation of thyroid gland by antibodies seen in Graves disease can also cause the growth of a goiter Male endocrinology Penis Contains erectile tissues corpus cavernosum and corpus spongeosum fill with blood when there is vasodilation causing erection Urethra extends from urinary bladder It will pass through the prostate gland Accessory structures Seminiferous tubules where sperm cells divide and develop Epididymis is where sperm are stored Vas deferens transport sperm where it will form the ejaculatory duct which joins into the urethra Seminal vesicles provide fluid and substrates like fructose to the sperm cells Prostate gland also secretes things like buffers to the semen Page 6 of 8 The penis and prostate both require dihydrotestosterone DHT a very potent androgen low DHT during development will cause no development of penis and instead the formation of female external genetalia Prostate continues to grow with age this can compress the urethra and urinary bladder which runs through it and can make It difficult to urinate Bulbourethral gland provide a small amount of lubricating fluid Both the testes and ovaries will develop from the same precursor organs in