Endocrine 2 Flashcards
What are the endocrine hormones?
Thyroxine(T4)
Triiodothyronine (T3)
The thyroid hormones play key roles in the regulation of the body development and govern the rate at which metabolism occurs in individual cells
These hormones are not essential for life but without them, cellular housekeeping moves at a slower pace, eventually influencing the ability of individual cells to carry out physiologic functions
What are the sources of iodine?
- fish(such as cod and tuna), seaweed, shrimp, and other seafood, which are generally rich in iodine
- Dairy products (such as milk, yogurt, and cheese) and products made from grains (like breads and cereals)
- fruits and vegetables contain iodine, although the amount depends on the iodine in the soil where they grew and in any fertilizer that was used.
- Iodized salt (table salt). Processed foods, however, such as canned soups, almost never contain Io sized salt
Give an overview of the thyroid
To maintain normal thyroid hormone secretion, 150 ug of iodine is the minimal intake necessary
- functional unit of the thyroid is the follicle
- lumen is filled with thyroglobulin which contains large number of thyroid hormone molecules
- surrounding the lumen are follicle cells, which function to both synthesize and release thyroid hormone
Explain thyroid hormone synthesis
- Iodine transport- iodine uptake is via a Na/K+-ATPase powered Na/I-symporter on the basal membrane
- This pump can raise the concentration of I- within the cell as much as 250 times that of plasma
- Along the apical membrane, the I- is transported into the lumen by a sodium-independent transporter called pendrin - Thyroglobulin synthesis- high molecular weight protein is synthesized in ribosomes, glycosylated in the endoplasmic reticulum and packaged into the vesicles in the Golgi apparatus
- Oxidation of I- to I^o
- The enzyme thyroperoxidase(TPO), which is located at the apical border of the follicle cell, catalyzes the oxidation
Note: TPO also catalyzes Io donation and coupling
- Iodination- As thyroglobulin is extruded into the follicular lumen, a portion (20%) of its tyrosine residues are iodinated
- The initial products of iodination are mono and diiodotyrosine (MIT & DIT) respectively, with the latter form predominating - Coupling- when two DITs couple, tetraiodothyronine (T4) is formed
- When one DIT and one MIT combine, triiodothyronine(T3) is formed. - Storage of thyroid hormone- enough hormones is stored as iodinated thyroglobulin in the follicular colloid to last the body fir 2-3 months
Note: when iodine is abundant, mainly T4 is formed but when iodine becomes scarce the production of T3 is increases
Explain stimulation of thyroid hormone release
Hypothalamic regulator:
Thyrotropin- releasing hormone(TRH) is released in response to thermoreceptor, metabolic signals and circulating levels of T4 and T3
- In the peripheral tissues, T4is converted to T3 by 5’-deiodinase
- Free T4 and T3 inhibit the synthesis and release of TSH by thryptrophs of the anterior pituitary
Note: because the main circulating firm is T4, it is T4 that is responsible for most of the negative feedback
Summarize thyroid hormone release
Hypothalamic nuclei secrete thyrotropin-releasing hormone (TRH) into portal vessels stimulating thyrotrophs of anterior pituitary to secrete TSH
This stimulates the thyroid gland, causing thyroids to secrete T4(50) and T3(1)
Within the thyrottoph, thyroid hormones decrease the sensitivity of the thyrotroph to TRH, thereby decreasing TSH secretion
Explain the hypothalamic pituitary thyroid axis
Thyrotropin releasing hormone (TRH) stimulates and somatostatin(SRIIF) inhibits thyroid-stimulating hormone(TSH) release by acting directly on the thyrotroph. The negative-feedback loops shown in blue inhibit TRH secretion and action on the thyrotroph, causing a decrease in TSH secretion. The feedback loops shown in red, stimulate somatostatin secretion, causing a decrease in TRH secretion. SRIF, somatostatin of somatotropin release-inhibiting factor
What are the overall effects on the thyroid by TSH?
Rapidly induced TSH effects
TSH tends to rapidly increase (minutes to hours) all steps in the synthesis and degradation of thyroid hormone, including:
- Iodide trapping
- Thyroglobulin synthesis and exocytosis into the follicular lumen
- Pinocytotic reuptake of iodinated thyroglobulin back into the thyroid follicular cell
- Secretion of T4 into the blood
Slowly induced T4 into the blood
Changes that occur more slowly (hours to days) in response to TSH include:
- Increased blood flow to the thyroid gland
- Increased hypertrophy/ hyperplasia of the thyroid cells, which initially leads to increased size of the gland
What is the physiologic action of the thyroid hoemone on metabolic rate?
Metabolic rate
- thyroid hormone increases metabolic rate, as evidenced by increased O2 consumption and heat production
- Increases activity of Na+/K+-ATPase in many tissue
- Thyroid hormone are necessary for brain maturation and essential for normal menstrual cycle
Note: hypothyroidism leads to menstrual irregularities and infertility
How does thyroid hormone affect carbohydrate metabolism?
Increases rate of glucose absorption from the small intestine
How does thyroid hormone affect lipid metabolism ?
- Accelerates cholesterol clearance from the plasma
- Required for the conversion 9f carotene to vitamin A
Note: hypothyroid individuals can suffer from night blindness and yellowing of skin
What are the cardiovascular effects of thyroid hormone?
- Have positive inotropic and chronotropic effects on the heart
- Cardiac output is increased, and both heart rate and stroke volumes are elevated
- Thyroid hormone in the normal range are required for optimum cardiac performance
What are the effects of thyroid hormone on growth and maturation ?
Thyroid hormones act synergistically with growth hormone and somatomedins to promote bone formation
-Without adequate thyroid hormone during the perinatal abnormalities rapidly develop in the nervous system leading to mental retardation (cretinism-a form of dwarfism with mental retardation)
What are the additional effects of Thyroid hormone?
- Maintains the ventilatory response to hypoxia increase erythropoieti, increase gut motility and bone turnover
- primary hypothyroidism is associated with increased prolactin
Note: TRH in excess amounts will stimulate prolactin
What is calcitonin?
Calcitonin is a peptide hormone secreted by a para follicular cells of the thyroid gland
Calcitonin lowers plasma calcium by decreasing activity of osteoclast, thus decreasing bone Reabsorption
Note: Calcitonin is not a major regulator of plasma calcium. No disease has been associated with excess or deficiency of this hormone
How does increased calcium affect bone reabsorption ?
- Increased plasma calcium leads to parafollicular cells which increase CT secretion. This leads to increased CT
- Increased CT secretion, then increases plasma CT which decreases bone Reabsorption which then decreases calcium release. Calcium release, decreases plasma calcium
- Increased plasma CT caused decreased phosphate Reabsorption in the kidneys, which leads to increased urinary excretion of phosphate. This results results in decreased plasma phosphate
- increased plasma CT results in decreased calcium Reabsorption in the kidneys. This leads to increased urinary excretion of calcium which also leads to decreased plasma calcium
What is the role of thyroid hormones for development of CNS?
- Inhibit nerve cell replication
- Stimulate growth of nerve cell bodies
- Stimulate branching of dendrites
- Stimulate rate of axon myelinization
What is the role of thyroid hormones on body growth?
Stimulate expression of gene for growth hormone in somatotrophs
Stimulate synthesis of many structural and enzymatic proteins
Promote calcification of bones
What is the role of thyroid hormones for basal energy economy of the body?
Regulate basal rates of oxidative phosphorylation, body heat production, and Cygwin consumption (thermogenic effect)
What is the role of thyroid hormone on intermediatory metabolism?
Stimulate synthetic and degradative pathways of carbohydrate, lipid, and protein metabolism
How do thyroid hormones affect TSH secretion?
Inhibit TSH secretion by decreasing sensitivity of thyrotrophs to thyrotropin releasing hormone
Describe parathyroid hormone secretion
Is a peptide hormone released from the parathyroid glands (chief cells) in response to low plasma Ca2+
Note: free Ca2+ in the plasma is the primary regulator of PTH
- The negative feedback relationship between plasma calcium and PTH secretion is highly sigmoidal, with steep portion representing the normal range of plasma free calcium. Free calcium is precisely regulated.
- to sense the free calcium, the parathyroid cells depend on high level of expression of calcium sensing receptors(CaSR)
How does parathyroid hormone regulate calcium homeostasis?
The actions of parathyroid hormone (PTH):
- Increase Ca2+ reabsorption in the distal tube
- Inhibits phosphate Reabsorption in the proximal tubule of the kidney
- Stimulates the 1-alpha-hydroxylase enzyme in the kidney, converting the inactive vitamin D to its active form [1, 25 di-OH D3]
- Causes bone resorption, releasing Ca2+ and Pi into the blood
What are the functions of 1,25-(OH)2Cholecalciferol (calcitriol)
Under normal conditions, Vit. D acts to raise plasma Ca2+ and phosphate. Thus, vitamin D promotes bone deposition. This is accomplished by:
- Calcitriol increases the absorption of Ca2+ and phosphate by the intestinal mucosa by increasing the production of the Ca2+ binding protein calbindin. The details of this pr9cess are poorly understood
- The resulting high concentrations of Ca2+ and phosphate in the Extracellular fluid exceed the solubility product, and precipitation of bone salts into bone matrix occurs.
- Calcitriol enhances PTH’s action at the renal distal tubule
Explain the regulation of Calcitriol secretion
-Vtiwmin D2 (ergocalciferol) is a vitamin and normally obtained from diet. It can be considered a prohormone.
A slightly different form D3 (cholecalciferol) is synthesized in the skin
After its conversion to 25-OH vitamin D3 in the liver, it can be stored in fat tissue
Note: 25-OH vitamin D3 represent the best measure of body stores of vitamin D, when a deficiency is suspected
Most of the 25-OH form, which is the immediate precursor for 1,25-OH vitamin D.
Ultraviolet light also evokes skin tanning, decreasing penetration of UV light and thus decrease the subsequent formation of D3.
