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76 Cards in this Set

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What is the primary bound protein storage form of thyroid hormones?
Thyroglobulin
How to epithelial thyroid cells respond to TSH?
They enlarge and change from squamous to cuboidal in shape.
What symptoms result from iodide deficiencies?
Mental and growth impairments (Cretinism), increased infant morbidity and mortality
What is the world's most common endocrine problem?
Iodide deficiency.
Name the two thyroid hormones.
Which is more active?
Thyroxine (T4) & Tri-Iodothyronine (T3)
T3 is the active form.
rT3 is also formed but is an inactive product.
Describe "Iodide Trap."
The active symport of Na+ and I- by an iodide carrier protein linked to Na/K ATPase on the basal membrane.
List the inhibitors of Iodide symport.
Anions like thiocyanate, perchlorate, and pertechnetate competitively inhibit active symport. Litium also inhibits symport.
Describe Thyroid Autoregulation.
Increases in iodide intake (high serum iodide) decreases the thyroid iodide uptake and hormone synthesis (Wolff-Chaikoff effect) and vice versa.
Describe the thyroid gland regulation.
The hypothalamus releases TRH which signals the anterior pituitary to secrete TSH to the thyroid. The hormone products, T3 and T4, inhibit the TSH secretion and the T3 inhibits TRH.
Hypothalamic Dopamine and Somatostatin exert tonic inhibition of TSH release.
What are the two subunits of TSH?
α-subunit: identical to FSH, LH, hCG
β-subunit: confers the biological activity
What enzyme couples and organifies the thyroglobulin to T3 and T4?
Thyroid Peroxidase
What do drugs for hyperthyroidism target?
Propylthiouracil (PTU) inhibits thyroidperoxidase, the enzyme necessary for iodination and coupling of T4/T3.
Describe the cause of Graves' disease.
TSH receptor antibodies are formed which mimic TSH and stimulate thyroid hormone production and growth of the thyroid gland. This is a common cause of hyperthyroidism.
To what proteins are most thyroid hormones bound?
Thyroxine binding globulin (TBG) mainly
Albumin
Thyroxine-binding prealbumin (TBPA) limited amts
What are the % secretions of thyroid hormones?
90% T4
5% T3
5% rT3
What enzyme converts T4 to T3?
5'-deiodinase
How does T3 function in a cell?
T3 acts as a steroid hormone and binds to the TR within the nucleus of the target cell. The activated TR binds heterodimerically with a retinoic acid receptor and allows a coactivation complex to bind and acetylates and activates gene transcription.
Is a TR without T3 bound active?
Yes, the TR-RXR heterodimer still forms and binds to a co-repressor complex which has a histone de-acetylase and represses the gene transcription near the TRE.
What are the causes of hyperthyroidism?
65-80% - Graves' disease
Others: thyroiditis, toxic thyroid adenoma, multinodular goiter, exogenous stimulants
What is the best way to test the thyroid state?
Indirect measure of T3/T4 through serum TSH levels because these levels change logarithmically compared to the arithmetic hormone levels.
What is Hashimoto's Thyroiditis?
An autoimmune disease with antibodies directed to the thyroid resulting in destruction of the thyroid and hypothyroidism.
What are another name for the anterior pituitary?
Adenohypophysis
What are two other names for the posterior pituitary?
Neurohypophysis and Pars nervosa.
What is the embryological origin of the anterior pituitary (adenohypophysis)?
The ectoderm of the roof of the primitive mouth forms Rathke's pouch which extends upwards.
What is the embryological origin of the posterior pituitary (neurohypophysis)?
The neuroepithelium of the diencephalon grows downwards.
Describe the blood supply to the anterior pituitary.
Hypophyseal Portal System:
Superior hypophyseal artery forms Primary Capillary Plexus in median eminence from hypothalamus.
Capillaries drain into the hypophyseal portal veins that deliver blood to the Secondary Capillary Plexus in Pars distalis.
Describe the blood supply to the posterior pituitary.
Inferior hypophyseal artery supplies it
What hormones are secreted by the chromophils of the anterior pituitary?
Basophilic (10%): FSH, LH, ACTH, TSH
Acidophils (40%): GH, Prolactin
What are the three regions of the anterior pituitary?
Pars Distalis
Pars Intermedia
Pars Tuberalis
What are the five types of chromatophils of the anterior pituitary?
somatotrophs (GH)
gonadotrophs (LH/FSH)
mammotrophs (Prolactin)
thyrotrophs (TSH)
corticotrophs (ACTH)
What two cell types are in the anterior pituitary?
chromatophils & chromatophobes
What are the hypothalamic releasing/inhibiting hormones secreted by the hypothalamic nuclei of the median eminence?
SRH (somatostatin/GH)
PRH (prolactin)
GRH (gonadotropins)
TRH (thyrotropins)
CRH (corticotropin)
What kind of capillaries are in the pituitary?
Fenestrated with diaphragms and a continuous basal lamina.
What is the Pars Tuberalis?
A region of the anterior pituitary which surrounds the infundibulum and secretes some LH/FSH.
What is the Pars Intermedia?
A region of the anterior pituitary which is the remnant of Rathke's pouch and separates the anterior and posterior pituitary. It produeces POMC.
Where are the hormones released in the posterior pituitary formed?
Within the nuclei of the hypothalmus:
Supraoptic forms ADH
Paraventricular forms Oxytocin
How are the hormones released in the posterior pituitary?
The hormones are formed by the secretory neurons of the hypothalamus and are transported down the unmyelinated axons to the Herring bodies. Pituicytes support these cells.
What kind of capillaries are in the adrenal glands?
Fenestrated with diaphragms and a complete basal lamina.
What is the embryological origin of the adrenal cortex?
coelomic intermediate mesoderm from the ridge which forms the gonads.
What is the embyrological origin of the adrenal medulla?
ectoderma neural crest cells
Describe the Adrenal Portal Blood Supply.
The superior, middle, and inferior suprarenal arteries enter the adrenal cortex which continue after a capillary plexus into venules in the medulla. This causes the steroid hormones formed in the cortex to go directly into the medulla.
What are the three distinct regions of the adrenal cortex (from the capsule to the medulla) and what hormone(s) does each secrete?
Zona Granulosa: mineralcorticoids (aldosterone)
Zona Fasiculata: glucocorticoids (cortisol)
Zona Reticularis: androgens (DHEA, DHEA sulfate, androstenedoine)
What are the histological characteristics of the zona glomerulosa?
~15% of the cortex, arranged in cords just below the capsule
What are the histological characteristics of the zona fasciculata?
~65% of the cortex, arranged in long cords with a "spongy" appearance due to the presence of many lipid droplets.
What are the histological characteristics of the zona reticularis?
~15% of the cortex, irregular cells forming irregular cords with some lipid droplets. May contain some lipofuscin and lies next to the medulla.
What is Conn's syndrome?
The overproduction of aldosterone.
What are three diseases associated with the adrenal cortex?
Cushing's syndrome: overproduction of glucocorticoids
Conn's syndrome: overproduction of aldosterone
Addison's disease: adrenocortical insufficiency
What are the characteristics of the cells of the adrenal medulla?
Considered to be modified sympathetic postganglionic neurons which have lost their dendrites and axons.
What unique histological chemical reaction occurs in the adrenal medulla?
The catecholamines (NE more than Epi) react with chromium salts and turn brown in color.
What is within the granules of cells of the adrenal medulla?
Catecholamines: Epi>NE
Chromogranins: bind catecholamines
Dopamine-beta-hydroxylase: converts dopamine to norepinephrine
What kind of capillaries supply the Islets of Langerhans?
fenestrated capillaries with diaphragms
What four cell types are found within the endocrine clusters, Islets of Langerhans, of the pancreas and what do they secrete?
α-cell: glucagon (20%)
β-cell: insulin (65%)
δ-cell: somatostatin (10)
f-cell: pancreatic polypeptide (5%)
What is the embryological origin of the pancreatic endocrine cells?
The same endodermal tissues as the exocrine pancreas, except a reticular network makes them a distinct entity.
What are the histological characteristics of a hypoactive thyroid follicle?
Squamous follicle epithelium with abundant, homogenously stained colloid.
What are the histological characteristics of a stimulated thyroid follicle?
Cuboidal/Columnar follicle epithelium with less colloid inside and regions (bubbles) lacking the colloid stain entirely.
What type of capillaries surround the follicles of the thyroid?
Fenestrated capillaries and lymphatics.
What are the characteristics of the Parafollicular "C" cells of the thyroid and what do they produce?
Cells with clearer cytoplasm located next to follicular epithelium cells. They do not touch the colloid. They form calcitonin to suppress osteoclasts and lowers blood calcium.
What two cell types make up the parathyroid glands and what do they secrete?
Chief cells (small basophilic): PTH
Oxyphil cells (larger acidophilic): unknown function
What is the embryologic origin of the pineal gland?
Derived from neural ectoderm.
What cells/structures make up the pineal gland and what do they form?
Pinealocytes: produces melatonin
Neuroglial cells: ie. astrocytes and microglia
Brain sand: calcified deposits which increase with age
What is hormone sensitivity?
The hormone concentration at which 1/2 of the max response is given.
It can be changed by altering the receptor affinity, the receptor number, or the specific rate-limiting post receptor events.
What are the three main classes of hormones?
amino acid derivatives
peptides and proteins
derivatives of cholesterol
How does cAMP activate PKA?
cAMP binds to the regulatory subunits on PKA which then release the active catalytic subunits to perform the PKA activity by phosphorylating serine and threonine residues.
How is PKA localized in the cell?
bound to specific sites via the regulatory subunits bind to A-kinase anchoring proteins (AKAP)
What enzymes initiate the conversion of arachidonic acid to prostaglandins and thromboxanes?
cyclooxygenases (COX1 and COX2)
How do tyrosine kinase associated receptors function?
They are similar to tyrosine kinases, however they cannot autophosphorylate. Rather, a non-covalently bound tyrosine kinase (JAK) will phosphorylate themselves and activate the residues.
What are STAT proteins?
They are TFs which when activated by tyrosine kinases will dimerize and activate or inhibit gene transcription.
What is body fuel homeostasis?
Constant internal environment maintained by physiologic mechanisms. Overall energy balance and constant body weight.
What is the caloric equivalent of carbohydrates and how much is stored?
4.2 kcal/gram
1% of caloric stores
What is the caloric equivalent of fats and how much is stored?
9.4 kcal/gram
76% of caloric stores
What is the caloric equivalent of proteins and how much is stored?
4.3 kcal/gram
23% of caloric stores
What are the three fundamental processes of body fuel homeostasis?
fuel storage and mobilization
maintenance of fuel levels in circulation
fuel uptake and use for the body's energy needs
What is the role of the peptide leptin in energy store regulation?
Plasma leptin levels increase with high adipose tissue and stimulate sympathetic neural activity to decrease food intake and increase metabolic rate, activity, body temp, and other hormones. These all work towards decreasing adipose tissue.
What is extracellular fuel homeostasis vs. intracellular?
Extracellular: maintenance of circulating fuel levels to provide for the necessary body functions.
Intracellular: use of the correct fuels by the correct tissues to provide the most efficient and necessary fuels for the running of the cell.
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