signaling pathways of endocrine hormones Flashcards
What factors use the intrisnic tyrosine kinase pathway?
insulin, IGF-1, FGF, PDGF, EGF. unifying theme: MAP kinase pathway. think about GROWTH FACTORS
What hormones use the cGMP pathway?
think about vasodilators: NO, atrial naturietic pathway
What are surprising (to me) hormones that use the steroid pathway?
vitamin D, T3/T4 (also aldo, cortsiol, estrogen, testosterone, progesterone)
What hormones use the receptor-associated tyrosine kinase pathway?
JAK/STAT pathway. this are the acidophiles (prolactin and GH) and the immunomodulators (cytokines, IFN)
What factors use the cAMP pathway?
most of the others: ACTH, FSH, LH, TSH, hCG, CRH, ADH, MSH, PTH, calcitonin, GHRH, glucugon.
I’m not going to worry about this list, as long as I understand FSH, LH, TSH, hCG, ADH, and glucugon, everything else is icing on the cake
What is sex hormone binding protein, and what is its clinical importance?
steroids must float about bound to specific binding globulins. in men, high sex hormone binding protein lowers free testosterone and causes gynecomastia. in women, low sex hormone binding protein raises free testoserone and causes hirsutism. OCPs and pregnancy increase SHBG (free estrogen levels remain unchanged)
What are the functions of thyroid hormones
bone growth, CNS maturation. increases beta 1 receptors in the heart to incr. CO, HR, SV, contractility.
incr. basal metabolic rate via Na/K/ATPase activity –> increases O2 consumption, RR, body temp.
incr. glycolysis, gluconeogenesis, lipolysis
(4 Bs: brain maturation, bone growth, beta adrenergic effects, increased basal metabolic rate)
regulation of thyroid hormones
TRH (hypothalamus) stimulates TSH (pituitary), which stimulates follicular cells. negative feedback by free T3 and T4 to anterior pituitary decreases sensitivity to TRH.
thyroid stimulating antibodies (graves disease) stimulate the follicular cells directly.
How do follicular cells function? ie. basic physiology of the thyroid gland
follicular cells make T3 and T4. T4 is the major thyroid product, and in many ways it is a prohormone. It can be converted to T3 in the periphery; T3 is much more potent (enzyme may be 5’ deiodinase).
thyroid gland has follicles filled with colloid containing thyroglobulin (made in RER by the follicular cells).
To make T4, the body must have iodine. Iodine is taken up from the blood at the base of the follicular cell. It is then oxidized to iodide by thyroid peroxidiase and released into the follicular lumen. tyrosine residues on the thyroglobulin are iodinated, resulting in MIT and DIT (also done by thryoid peroxidase). To release T3/T4, the thyroglobulin/MIT/DIT type stuff is taken up into the follicular cell, undergoes proteolysis, and is released as T3/T4.
Wolff-Chiakoff effect
excess iodine temporarily inhibits thyroid peroxidase, causing decreased iodine organification and decr. T3/T4 production
thyroid binding globulin
protein that binds most T3/T4 in the blood. only free hormone is active. decrease in TBG is seen in hepatic failure; increase in TBG is seen in pregnancy or OCP use because estrogen promotes release of TBG.
what drugs are used to treat hyperthyroidism? side effects? differences?
propylthiouracil and methimazole
propylthiouracil inhibits both peroxidase and 5’-deiodinase (peripheral conversion of T4 to T3). propylthiouracil is also safe in pregnancy
methimzaole inhibits peroxidase only. It is a teratogen that can cause apalsia cutis in the fetus (missing skin).
Toxicity of both methimazole and propylthiouracil: agranulocytosis (rare), aplastic anemia, hepatotoxicity (propylthiouracil).
What drugs are used for thyroid hormone replacement? Toxicity?
levothyroxine, triiodothyronine.
used for hypothyroidism and myxedema.
can cause tachycardia, heat intolerance, tremors, arrhythmias.
use of GH
GH deficiency, Turner syndrome. could cause insulin resistance
demeclocycline
ADH antagonist (member of tetracycline family). this would be used in SIADH. toxicity: nephrogenic diabetes insipidus, photosensitivity, abnormalities of bone and teeth.
