Lecture 4 Flashcards by Sara Richmond

_______________ made by parvocellular neurons of the paraventricular nucleus (PVN)

Thyrotropin releasing hormone (TRH):

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______________________

: produced by thyrotrope cells in the anterior pituitary

Thyroid stimulating hormone (TSH)

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Thyroid follicle cells make ______________________ ______________

tetraiodothyronine or thyroxine (T4) and triiodothyronine (T3)

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________________ are protein secreting cells that line a lumen filled with a fluid called colloid. These make T4 and T3

Follicular cells

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__________________ contains thyroglobulin, a large glycoprotein molecule secreted from follicular cells that acts as a store for thyroid hormone

Colloid

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_______________ make the hormone calcitonin

C/clear/parafollicular cells

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Thyroid hormone is stored on the _______________

thyroglobulin molecule in colloid

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Each thyroglobulin molecule contains ___________________

70 tyrosine residues

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________________ is secreted into the lumen and iodonated

Imported by ____________when the follicle is stimulated

Thyroglobulin

phagocytosis

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_____________ is a pool for thyroid hormone

Colloid/thyroglobulin

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______________

increased thyroglobulin (Tg) phagocytosis
increased production of T3/T4

Acute TSH stimulation:

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_____________

increased iodide uptake
increased Tg synthesis
follicular cell proliferation

Chronic TSH stimulation:

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____________is the primary secretory product from follicular cells in the thyroid

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__________ is considered the active form of T4 • (3-4x more potent than T4)

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• Multiple tissues convert ____________ • (e.g. liver, kidney, brain)

T4 to T3

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A precursor hormone that is converted to an ______________in another tissue or cell.
a precursor hormone Usually has no effects or weaker effects
• Applies to protein and steroid hormones

active hormone

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• A large peptide/protein precursor that is cleaved to form _________________

a shorter active peptide.

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A steroid that is converted to another steroid at the target tissue
• If there are three steps____________________

, then pre-pro-hormoneàpro-hormoneàactive hormone.

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• Which thyroid hormone is the prohormone? What other hormones could be pro- hormones?

pro hormone: T4

Active hormon T3

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How does circulation of a prohormone allow for regulation of thyroid hormone effects?

allows for thyroid regulation when binding site is plentiful

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_____________or iodide transporter scavenges and traps ingested iodide in thyroid follicular cells
>90% of all retained iodide is in the thyroid

Iodide trap

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Na+ gradient set up by an _________________

ATP-dependent sodium potassium transporter

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_____________ moves I- into cell along with Na+, which is moving down its concentration gradient
Voltage-gated K+ channel restores potassium balance

Sodium-iodide symporter:

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___________ –thyroid, liver, kidney, pituitary

Preferred substrate: rT3

D1 or Dio1

_________________ – thyroid, brain, pituitary, brown adipose tissue, placenta, innate immune cells Preferred substrate: T4

D2 or Dio2

_____________– placenta and brain primary role: inactivating

D3 or Dio3

__________________ are similar to conversion of cortisol or cortisone in the brainàinactivation

Conversion to rT3 or T2

__________________ requires active transport in and out of cells

Thyroid hormone

Use two families of transporters, __________________-________________________

monocarboxylate transporters (MCT) and L-amino acid transporters (LAT)

Specific cells use different ___________________

transporters (MCT8 in thyroid)

Carrier proteins in the circulation

Thyroxin-binding globulin: major carrier • Albumin • Transthyretin: transports thyroxine and retinol

________________ modulate transcription through thyroid response elements (TRE)

Nuclear receptor transcription factors:

______________ Thyroid hormone increases basal metabolic rate, body heat production, fat mobilization, and glucose in the blood

Metabolism:

_______________-Thyroid hormone regulates _________________, as evidenced by the growth-retardation observed in thyroid deficiency

Growth:

________________: High thyroid hormone levels increased heart rate, cardiac contractility and cardiac output

Cardiovascular system

_________________: Low thyroid hormone levels lead to feelings of mental sluggishness, high levels induce anxiety

Central nervous system

______________: Hypothyroidism is commonly associated with infertility

Reproductive system

_______________ • Insufficient daily iodide intake • T3 and T4 levels fall à TSH levels rise à follicle cell proliferation (hypertrophy) • Compensatory adjustments by follicle cells can limit impact • Higher T3:T4 ratio with incomplete iodonation • Thyroid function not necessarily compromised

Endemic Goiter

Thyroid-stimulating immunoglobulin (TSI) hyperstimulates the thyroid gland *autoimmune-mediated hyperthyroidism*

Graves Disease

Symptom of graves disease

Exophthalmos (puffy, bulging eyes) caused by cellular autoimmune response to TSH-R on adipocytes in orbit of eye

- Most common cause of hypothyroidism in the US - Antibodies attack thyroid follicle cells - Chronic inflammation of the thyroid gland

Hashimoto’s Disease

Hashimoto's disease causes

Impairs ability to make thyroid hormones

_____________ Insufficient daily iodide intake - Reduced negative feedback leads to follicle cell proliferation - Enlarged thyroid - Thyroid function not necessarily compromised

Endemic goiter:

_______________: Autoimmune-mediated hyperthyroidism - Hyperstimulation of the thyroid gland - Enlarged thyroid - Thyroid function not necessarily compromised

Graves Disease

_____________Autoimmune-mediated hypothyroidism - Reduced negative feedback leads to follicle cell proliferation - Enlarged thyroid - Failure at the level of the thyroid gland

Hashimoto’s Disease:

It is critical to maintain_____________within a tight normal range. Deviations above or below the normal range frequently lead to serious disease.

blood calcium concentrations

_________________ low blood calcium concentration can lead to increased neuromuscular excitability and include muscle spasms, tetany (involuntary muscle contractions), and cardiac dysfunction.

Hypocalcemia:

_______________high blood calcium concentration can lead to diffuse precipitation of calcium phosphate in tissues, leading to widespread organ dysfunction and damage.

Hypercalcemia:

______________ Intracellular free calcium concentrations fluctuate greatly, 100 nM to 1 uM, due to release from cellular stores or influx from extracellular fluid. These fluctuations are integral to calcium's role in intracellular signaling, enzyme activation, and muscle contractions.

Intracellular calcium:

_____________ The concentration of ionized calcium in blood and ECF is approximately 1 mM, far higher than the concentration within cells.

Calcium in blood and extracellular fluid:

____________: A vast majority of body calcium is in bone. Within bone, 99% of the calcium is tied up in the mineral phase, but the remaining 1% is in a pool that can rapidly exchange with extracellular calcium.

Bone calcium

Calcium Sources • The ________ is where dietary calcium is absorbed from the diet •________ is the largest reservoir of calcium. • The __________ can reabsorb almost all of the calcium that enters glomerular filtrate back into blood to preserve blood calcium levels

small intestine Bone kidney

_______________ of the parathyroid gland make parathyroid hormone (PTH)

chief cells

__________of the thyroid gland make calcitonin (CT) | Hormonal Regulation of Calcium

c cells

Express Calcium Sensing Receptors (CaSR)

Chief cells and C cells

G-protein coupled receptor that binds free calcium, signals through ____________

cAMP

++++suppresses PTH production and release | ++++++++ control CT production and release

In chief cells: | In C cells:

-Increases blood concentrations of calcium • Produced in response to hypocalcemia • Facilitates mobilization of calcium and phosphate from bone. • Maximizes tubular reabsorption of calcium within the kidney. This activity results in minimal losses of calcium in urine • Stimulates the kidney to produce the biologically-active form of vitamin D, which facilitates absorption of calcium from the small intestine

Parathyroid hormone (PTH) effects

___________- • Made by C cells of the thyroid gland • Produced in response to hypercalcemia • Enhances excretion of calcium into urine • Inhibits bone resorption, leading to less calcium from bone into blood

Calcitonin (CT)