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225 Cards in this Set
- Front
- Back
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How does the hypothalamus signal to the pituitary?
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Via blood vessels in the pituitary stalk
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What is the hypothalamic/hypophyseal portal system?
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From the hypothalamus to the anterior pituitary
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How many hormone producing cells are in the anterior pituitary?
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6
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What type of neurohormones does the hypothalamus secrete to act on the anterior pituitary?
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Releasing or inhibiting hormones
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What are the glycoproteins?
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FSH,LH, TSH, HCG
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What are the steroids?
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Aldosterone, Cortisol, Estradiol, Progesterone, Testosterone, Vitamin D
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What are the amines?
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Epinephrine, Thyroxine, Triiodothronine, Melatonin
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What is the other type of hormone?
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Polypeptide
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What is an example of a non-hormonal feedback mechanism?
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Increased calcium levels act on the parathyroid glands to stop them from releasing PTH- which results in a decrease in Ca.
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What is an example of a hormonal feedback mechanism?
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Cortisol acts on both the hypothalamus to stop CRH secretion, and the anterior pituitary to stop ACTH secretion which ultimately leads to lower cortisol
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What type of tissue, histologically is that of the adenohypophysis?
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Endocrine
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What type of tissue, histologically is that of the neurohypophysis?
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Neural
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What are the six adenohypophysis hormones?
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ACTH, GH, Prolactin, TSH, FSH/LH
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What are the two neurohypophysis hormones?
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Vasopressin (ADH) and Oxytocin
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Where are vasopressin and oxytocin synthesized?
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In two hypothalamic nuclei, the supraoptic nuclei and and paraventricular nuclei)
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Where are vasopressin and oxytocin secreted and how do they get there?
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They are transported via carrier molecules called neurophysins down the pituitary stalk to the posterior pituitary.
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What are the two functions of oxytocin?
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Parturition (increase uterus contraction in pregnancy) and milk ejection
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What are the two structural components of the thyroid gland?
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The follicle and the parafollicular cells
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What is in the follicle?
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Colloid
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What is colloid?
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Colloid is a major component of thryoglobulin
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What does thyroglobulin contain?
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The thyroid hormones
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What are the thyroid hormones?
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T3 + T4
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What controls the synthesis of thryoglobulin?
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TSH, released from the anterior pituitary
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What do the parafollicular cells release?
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Calcitonin
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What is throxine (T4) made of?
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Two diiodotyrosines (DIT)
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What is triiodothronine made of? (T3)
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One monoiodotyrosine (MIT) and one diodotyrosine (DIT)
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What type of feedback does T3 and T4 exert?
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They exert a negative feedback by stopping the synthesis of hypothalamic hormone TRH and the anterior pituitary hormone TSH
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How does TSH act to promote T3 and T4 synthesis?
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Induces activity of adenyl cyclase and the production of cAMP
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How is a non-toxic goiter formed?
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Iodine difficency, T3, T4 decrease, therefore no negative feedback on TSH, and the thyroid cells are stimulated- enlarged thyroid
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How do T4 and T3 influence metabolism?
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They increase the BMR (Basic metabolic rate)- increasing the breakdown of carbs, proteins and fats
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How do thyroid hormones influence growth?
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Without these, growth hormone cannot act to stimulate growth
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What is thyroid required for with the CNS?
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Brain development, stimulate synthesis of NGF( Nerve growth factor)
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What are the three mechanisms by which thyroid hormones act?
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Nuclear- effect proteins synthesis
At the inner mitochondrial membrane- increase O2 consumption At plasma membrane, increase up take of aa's |
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What is Myxedema?
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Primary hypothyroidism
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What are some causes of PRIMARY hypothyroidism?
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Atrophy of the thyroid
Autoimmune disease- Hashimoto Non-toxic goiter |
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What is secondary hypothyroidism?
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No synthesis of TSH by the anterior pituitary
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What is tertiary hypothyroidism?
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No TRH synthesis by the hypothalamus
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What is infantile hypothyroidism?
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No thyroid- dwarfism and cretinism similarities
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What is Graves diseases?
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A type of primary hyperthyroidism. It is when a TOXIC goitre is formed.
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How is the toxic goitre formed?
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It is an autoimmune disease where lymphocytes produce LATS (Long Acting Thyroid Stimulator) which mimic TSH
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What is the second type of primary hyperthyroidism?
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Thyroid cancer, where thyroid hormones are synthesized without TSH stimulation
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What is secondary hyperthyroidism caused by?
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No negative feedback of T3/T4- TSH synthesiszed. Pituitary tumor
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What is tertiary hyperthyroidism caused by?
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No negative feedback of T3/T4- TRH synthesized. Hypothalamic tumor
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What is propylthiouracil?
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It is an antithyroid drug that blocks the addition of iodine to thyroglobulin, can treat hyperthyroidism
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What is PTH?
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Parathyroid hormone, produced by the parathyroid glands increases the circulating levels of calcium
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What does calcitonin do?
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Lowers the circulating levels of calcium
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What does Vitamin D do?
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It increases the circulating levels of calcium
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Where is calcium absorbed?
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In the duodenum and jejeunum of the digestive tract
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How does calcitonin decrease circulating levels of calcium?
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Increases calcium deposition in bone
Increases kidney excretion of calcium into the urine |
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What is parathyroid hormone secreted from?
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Parathyroid chief cells
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Where are parathyroid glands located?
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There are 4 on the back of the thyroid
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How does PTH increase body calcium?
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Promoting bone demineralization, Increasing Ca reabsorption in the PCT,
Stimulate conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (ACTIVE FORM) Facilitate absorption of Ca from Gut |
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What controls PTH release?
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Circulating levels of calcium
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What type of mechanism does PTH use?
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Second messenger (adenyl cyclase activation and production of cAMP)
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What are some symptoms of HYPOPARATHYROIDISM?
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Hypocalcemia, low production of active VD3, Tetany and convulsions
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What are some symptoms of HYPERPARATHYROIDISM?
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Besides obvious,
kidney stones Severe: cardiac arrythmias, depressed neuromuscular excitability, calcium deposition on blood vessel walls, and cartillage |
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Why is Vitamin D not technically a vitamin?
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It is synthesized from a cholesterol metabolite
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What are the four steps to Vitamin D?
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1- UV light combines with 7-dehydrocholesterol
2-25-hydroxylation in the liver 3- 1-hydroxylation in kidney 4- 1,25-dihydroylation by PTH |
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What are some functions of Vitamin D?
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Increase Ca absorption in intestine, antinflammitory, anticancer
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What is Rickets?
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A form of Vitamin D diffiency, resulting in deficient bone mineralization. Can be caused by a lack of access to UV
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Why is Rickets more severe in darker skinned people?
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They have a skin pigment, melanin, that blocks UV.
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What is osteomalacia?
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Soft bone, can be caused by renal failure
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Why would renal failure result in Vitamin D difficiency?
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Decreased 1-hydroxylation in the kidney
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Where are the adrenal glands located?
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Adjacent to the upper surface of the kidneys
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What are the two types of adrenal gland tissue?
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The cortex and the medulla
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What does the cortex look like?
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Large, lipid containing epithelial cells
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What does the medulla look like?
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Chromaffin cells- fine brown granules when stained with potassium bichromate
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What is the cortex derived from?
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Mesoderm
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Where is the medulla derived?
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Neural Crest
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What does the cortex?
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Steroid hormones:
glucocorticoids, mineralcorticoids, and progestins |
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What does the medulla produce?
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Catecholamines epinephrine and norepinephrine and some peptide hormones (enkephalin, dynorphin, and atrial natriuretic peptide)
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What are the three layers of the Adrenal Cortex?
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Zona glomerulosa
Zona fasciculata Zona reticularis |
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What does the zona glomerulosa produce?
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Mineralcorticoids
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What does the zona fasciculata produce?
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Glucocorticoids (cortisol)
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What does the zona reticularis produce?
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Glucocorticoids, progestins, androgens, and estrogens
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Which areas of the adrenal cortex does ACTH control?
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Zona fasciculata and zona reticularis
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What is 18-alpha-hydroxylase present and what does it do?
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Zona glomerulosa- key in synthesis of aldosterone (mineralcorticoid)
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Where is 17-alpha-hydroxylase present and what does it do?
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It is present in the zona reticularis and fasciculata- it is responsible in glucocorticoid synthesis
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What does aldosterone do?
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It increases the reabsorption of Na by the kidney
Affects loss of K+ and H+ which balance the reabsorption of Na |
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What do glucocorticoids do?
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They have an effect on salt retention, protein and carb metabolism, and lipid metabolism, anti-inflammatory, immunosuppresive, lose calcium from bone leading to osteoporosis
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How does glucocorticoid secretion lead to increased blood glucose levels?
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Promotes gluconeogenisis by stimulating the release of gluconeogenis enzymes in hepaocytes. They also decrease glycolysis (glucose breakdown) and decrease cell glucose uptake
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What type of diabetes can excess glucocorticoids lead to?
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Adrenal diabetes
and eventually beta cell destruction leading to diabetes mellitus |
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What is propiomelanocortin?
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Precursor to ACTH
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What is congenital adrenal hyperplasia?
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No cortisol production, ACTH is not inhibited by negative feedback- too much
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How does ACTH perform its action on the adrenal glands?
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Binds to a specific receptor on the membranes of the zona fasciculata and the zona reticularis- adenyl cyclase and cAMP production
Activates steroidogenic enzymes |
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What is the diurnal rhythm of ACTH and cortisol secretion?
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The levels are minimum at midnight and maximum in the morning
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Which disease can destroy this diurnal rhythm?
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Cushing's disease
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How does stress effect glucocorticoids?
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Increase in release of CRH, Cortisol and ACTH
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What is Addison's disease?
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Hypofunction of the Adrenal cortex
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Which disease can result in this hypofunction?
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Tuberculosis
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What is Cushing's diseased?
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Hyperfunction of the Adrenal cortex
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What is Cushing's diseased caused by?
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Increased circulating levels of ACTH resulting in adrenal cortex hyperplasia
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What is the percentage of the pancreas that is ENDOCRINE?
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1%
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What are the two cell types in the islets of langerhaans?
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60% Beta cells and 25%alpha cells, detla cells, etc..
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What do beta cells produce?
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Insulin
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What do alpha cells produce?
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Glucagon
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What do delta cells produce?
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Somatostatin
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What is insulin?
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It is a hormone that works to DECREASE blood glucose
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What is diabetes mellitus?
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When beta cells are destroyed- glucose accumulates due to the inefficiency of most cells to take up glucose without insulin
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What is used as an energy source?
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Fat
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What is the problem with using fat as an energy source?
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Oxidation of free fatty acids are incomplete.
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What is increased in circulation due to this incomplete free fatty acid production?
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Acetoacetic acid, B-hydroxybutyric acid, and acetone
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What is type II diabetes?
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Hyporesponsiveness to insulin
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What is a hypoglycemic coma?
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Availability of glucose for the brain is not sufficient, blood glucose is only 20-30 mg/100mL
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Which type of diabetes is associated with obesity?
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Type 2. If you overeat, prolonged high insulin levels decrease the number of receptors in a process known as downregulation
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What would the glucose tolerance test be like for a normal person/person with diabetes?
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A person with diabetes has a lower glucose tolerance. After administering glucose to a NORMAL individual, levels return to normal after 2-3 hours. A diabetic individual will have a higher increase in glucose and it will take longer for the blood glucose level to go back to normal.
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What are some body mechanisms to ensure proper levels of body glucose?
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Beta cells sense body glucose levels
Gastrin and vagal impulses act to increase insulin before the meal even causes a rise in blood glucose. |
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What does glucagon do?
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Raise blood sugar by promoting gluconeolysis and gluconeogenisis
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Where is growth hormone produced?
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In the anterior pituitary
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What does growth hormone stimulate in the liver?
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Somatomedins
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What are somatomedins?
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IGF 1 and 2. Can bind to insulin receptors also.
Increases growth and stimulates protein synthesis |
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Which two hormones regulate GH?
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Growth hormone releasing hormone- stimulates release
Somatostatin- inhibits release |
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What is gigantism?
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Excess of GH in YOUTH
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What is acromegaly?
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Excess of GH later in life (adulthood)
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What are some symptoms of acromegaly?
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many bones are LONGER and HEAVIER
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What are the primary reproductive hormones in the male?
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Gonads, testes
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What are the primary reproductive organs in the female?
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Ovaries
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What are the two functions of gonads?
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Gametogenisis (production of reproductive cells, gametes)
Secretion of sex hormones |
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What are the gametes in the male and female?
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Spermatazoa in males
Ova in females |
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What are the sex hormones produced?
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Testosterone- male
Estrogen and Progesterone in female |
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What stimulates development of gametes and secretion of sex hormones?
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Gonadotropin releasing hormone is released in the hypothalamus and goes to the anterior pituitary where follicle stimulating hormone and lutineizing hormone are released.
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What is a non-reproductive function of estrogen?
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Prevents osteoporosis
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What produces inhibin and what does it do?
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Gonads- negative feedback on anterior pituitary
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When does the male produce his gametes?
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Constantly renewing the pool throughout his life to keep it constant
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Where does spermatogenesis take place?
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The seminiferous tubules of the testes
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Where are Leydig cells located and what are they responsive to?
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Outside the seminiferous tubules, and they are responsive to LH
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Where are Sertoli cells located and what are the responsive to?
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Within the seminiferous tubules, and they are responsive to FSH
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What do Leydig cells synthesize?
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Androgens
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What do the Sertoli cells synthesize?
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Androgen Binding Protein and inhibin
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What is the dependence of spermatogenisis on androgen concentration?
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In the seminiferous tubules, the concentration must be approximately 10 times higher than in circulation.
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What does ABP do?
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Ensures that this high concentration of androgens is attained in the seminiferous tubules
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What is the hypothalamic-pituitary-leydig cell axis?
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GnRH stimulates LH+ FSH- stimulate androgen release
Androgen inhibits GnRH, LH and FSH |
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What is the hypothalamic-pituitary-seminiferous-tubules axis?
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inhibin inhibits FSH release ONLY
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What are the functions of the ovary?
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Production of mature oocytes and secretion of sex hormones
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Do females continually produce oocytes like males continually produce sperm?
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NO. At birth, ovary contains 2 million immature ova which are the whole lifetime supply.
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How much ova are left at puberty?
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400,000
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What are oocytes surrounded by?
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A single layer of granulosa cells, and a basement membrane
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What are these oocyte/layer combinations called?
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Primordial follicles
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After an unknown initiating event, what do primordial follicles become?
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Primary follicles
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What is the growth of primary follicles controlled by?
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Gonadotropins and steroid hormones
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What is atresia?
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Degeneration of follicles
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What is the first layer that grows around the oocyte?
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The Zona pellucida
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What is characteristic about the formation of primary follicles?
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The granulosa cells divide and increase in layer number
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What are FSH and estrogens important for in this step?
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Influencing the granulosa cells division
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What is estrogen involved in?
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Expression of LH receptors on the surface of granulosa cells
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What is the difference between a primary follicle and a secondary follicle?
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Secondary follicle has receptors for LH, FSH, and estrogen. It has an antrum which contrains the secretions of the granulosa cells
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What happens to form the preovulatory follicle?
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Granulosa cells elaborate follicular fluid. This is the mature follicle
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What are theca cells?
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Steroid producing cells that are formed from stroma surrounding the follicle differentiating.
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What do these theca interna cells do?
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Collaborate with granulosa cells to increase the synthesis of estrogen
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Why does follicular atresia take place?
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So that only one oocyte will ovulate per cycle
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What is ovulation?
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Follicular rupture and release of oocyte
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What is a ruptured follicle transformed into?
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The Corpus Luteum
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What does the corpus luteum secrete?
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Progesterone
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What would prevent the dropping off of huge levels of estrogen and progesterone production by the corpus luteum?
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Implantation of fertilized ovum
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If implatation occurs, what is the corpus luteum transformed to?
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The corpus luteum of pregnancy?
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What is the corpus luteum of pregnancy responsible for?
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Synthesis of progesterone and estrogens and proper endocrine environement for pregnancy until this role is taken over by the placenta
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What induces luteal regression and how?
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Prostaglandins may play a role. They do this by decreasing LH binding.
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What does luteal regression result in?
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A decrease in plasma estrogen and progesterone which could stimulate the next reproductive cycle
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What happens before the first day of the menstrual cycle?
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The endometrium (lining of uterine cavity) proliferates due to the presence of estradiol
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What does progesterone induce?
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Appearance of glycogen secreting glands
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What happens at Day 1?
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First day of detectable vaginal bleeding- deterioration of uterine endometrium
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What are the levels of estradiol and progesterone when bleeding begins?
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Low
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What do these low levels lead to?
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Increased levels of FSH release from anterior pituitary
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What do normal levels of estradiol do?
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Block FSH release
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What also contributes to the rise of FSH during the 5 days of bleeding?
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Decrease in inhibins
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What does the increased FSH do?
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Follicles develop. FSH stimulates the granulosa cells to proliferate
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What does this proliferation of granulosa cells lead to?
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Estrogen
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What happens at day 8?
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1 follicle is dominant, others degenerate by atresia
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What does the increased estrogen cause?
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Uterine endometrium proliferation
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What is the endometrium like at day 13?
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Very thick
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What happens at this point under the influence of estradiol?
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Induction of progesterone receptors into the endometrium
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What does moderate estradiol do?
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Negatively feedback on FSH release
Stimulate LH synthesis Block LH release Increase pituitary sensitivity to GnRH |
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What do elevated estradiol concentrations do at day 14?
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Stimulate LH release- resulting in an LH surge (LH had built up in pituitary area because it had been blocked from release)
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What are the two feedback mechanisms that estrogen is involved in?
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Negative on LH release
Positive on GnRH sensitizing resulting in a higher LH synthesis |
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What does the LH surge cause?
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Follicle to rupture and ejection of ovum
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How do oral contraceptives work?
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They maintain moderate levels of estrogen and progesterone suppress release of LH and FSH and thus follicle maturation and ovulation
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What happens to the endometrium under the influence of progesterone?
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It becomes glandular, it is ready to receive the embryo
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What happens in the luteal phase?
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14 days- luteolysis occurs, if no implantation, steroid hormone levels drop, endometrium degenerates menstruation begins
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At ovulation, what happens to the unfertilized egg?
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It is taken by the fimbria of the oviduct (fallopian tube) and is propelled towards the lumen of the uterus
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How does fertilization occur?
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Sperm will travel in the fallopian tube and will fertilize the egg.
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What happens to the fertilized egg as it is transported from the oviduct to the uterine lumen?
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It develops to the blastocyst stage
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What does the blastocyst differentiate into?
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The trophoblast and the inner cell mass
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What will the trophoblast become?
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The placenta
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What will the inner cell mass become?
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The embryo
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What does the trophoblast secerete around the time of implantation?
|
Human chorionic gonadotropin
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What does HCG do?
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It has LH like properties and stimulates the corpus luteum to continue secreting hormones
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What happens at the 12th week of pregnancy?
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The placenta takes over the endocrine function of the corpus luteum
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What is the fetoplacental unit?
|
The fetus + placenta form this
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What does the fetal liver acquire?
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Important function in estrogen synthesis
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What does the placenta produce?
|
Human chorionic somatotropin, relaxin and progesterone
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What forms the basis of the pee test for pregnancy?
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HCG- appears quickly in the urine after impregnation
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What is lactation?
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The secretion of milk by the breast
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What is progesterones role in lactation?
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Stimulation of alveoli formation
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During pregnancy, what hormones influence the formation of ductal and alverolar structures?
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Estrogen, progesterone, prolactin and human placental lactogen
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What hormones are responsible for mammary gland growth?
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GH, cortisol and thyroxin
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What is responsible for milk production in pregnancy?
|
Prolactin
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What is responsible for preventing milk ejection during pregnancy?
|
High estrogen levels
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What is lactational amenorrhea?
|
During nursing, FSH and LH secretion is inhibited and the entrance of the reproductive cycle is blocked.
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What is menopause?
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The loss in steroid hormone production
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What causes this?
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Depletion of follicles
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What causes the high release of FSH and LH in pregnancy?
|
The stopping in steroid hormones eliminates the negative feedback loop that is normally placed on FSH + LH
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Can fertility be restored by hormone replacement therapy?
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NO. Primary reason for menopause is the depletion of follicles
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What are some substances that use nuclear signalling?
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Small lipophillic molecules and glucose
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Which substances use membrane receptors that result in nuclear signalling?
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Peptide hormones, small hydrophillic molecules
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How do nuclear receptors exert their effects?
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Regulating transcription of genes, leading to a change in protein levels
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What is PXR used to screen for?
|
The capacity of small molecule drug candidates to activate their own metabolism and the metabolism of other drugs
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What happens to drugs that potently activate PXR's?
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They are eliminated from development. You don't want drugs to metabolzie themselves
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What do PPAR's do?
|
Control lipid metabolism and adipogenisis
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What are the three PPAR receptors?
|
alpha beta and gamma
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What does PPAR stand for?
|
Peroxisomal proliferator activator receptor
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Where PPARalpha receptors most highly expressed?
|
In tissues that display high rates of fatty acid metabolism
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What do PPARalpha receptors bind?
|
Fatty acids and their metabolites
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How can fatty acids control their own metabolism?
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Through PPARalphas, by inducing the expression of genes encoding metabolic enzymes required for fatty acid catabolism (breakdown)
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Where are PPARgamma receptors most highly expressed?
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Adipose tissue, intestine, and spleen
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What is a high affinity ligand for PPARgamma
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thiazolidinedione
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What type of drugs were TZD's initially developped for?
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Anti-diabetic drugs
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What is the real essential function of PPARgammas?
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Apidogenisis
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How then, do PPARgammas stimulation allow TZD's to be anti diabetic?
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They remove free fatty acids, therefore forcing the cells to rely on glucose for metabolism
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What does FXR control?
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Bile acid metabolism
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How is cholesterol metabolism controlled?
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Feedforward mechanism, production of CYP7A, enzyme to convert to bile acids
Feed back- elevated levels of bile acids inhibit bile acid synthesis |
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Where is FXR orphan receptor most highly expressed?
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Liver and intestine
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What is FXR activated by?
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The primary bile acid chenodeoxycholic acid
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Why are bile acids important?
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They represent solubulized excreted forms of cholesterol
They are both fat and water soluble, they function to facilitate absorption of fats and fat soluble vitamins in the small intestine |
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What are two pieces of evidence that FXR is a bile acid receptor?
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1- bile acid bound FXR represses CYP7A synthesis- demonstrates feedback mechanism
2- FXR activates expression of intestinal bile acid binding protein |
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What are some diseases that have demonstrated north-south gradients?
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Colon + prostate cancer, Crohn's disease, MS (autoimmune diseases), infectious diseases
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