Lecture 25: Endocrine System II

thymus

site of maturation for T cells (immune defense); undergoes involution with age

hormones secreted by thymus

-thymopoietin
-thymosin
-thymulin

functions of hormones secreted by thymus

lymphatic organs development; regulate the development and activity of T cells

shape of thyroid gland

it is shaped like a butterfly wrapped around the trachea, with 2 winglike lobes usually joined inferiorly by a narrow bridge of tissue (the isthmus)

follicle

sac of the thyroid gland; each is filled with a protein-rich colloid lined by a simple cuboidal epithelium of follicular cells and parafollicular cells

what protein makes up the colloid of the thyroid gland?

thyroglobulin (Tg)

what do follicular cells of thyroid gland secrete?

thyroid hormone (TH)

parafollicular cells of thyroid gland

AKA clear (C) cells; located between the follicles; they secrete calcitonin

what are the two forms of thyroid hormone?

-T4: tetraiodothyronine
-T3: triiodothyronine

what does the number in T4 and T3 refer to?

the number of iodines in the molecule

what are the two main components of T3 and T4

iodine and tyrosine

steps in TH synthesis and secretion - 1

iodine from the diet is transported from the bloodstream into the colloid by sodium/iodide symporters (movement of iodine against concentration gradient)

steps in TH synthesis and secretion - 2

iodine (I2) forms through oxidation of iodide (I-) by thyroperoxidase

steps in TH synthesis and secretion - 3

Iodine binds tyrosine residues on thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT); this process is AKA "organification of iodide"

steps in TH synthesis and secretion - 4

When the follicle cells receive TSH, they absorb droplets of thyroglobulin by pinocytosis

steps in TH synthesis and secretion - 5

Endosome fuse with lysosomes which contain hydrolytic enzymes that digest thyroglobulin, thus releasing free thyroid hormones

steps in TH synthesis and secretion - 6

Free thyroid hormone diffuses into the blood

steps in TH synthesis and secretion - 7

TH is hydrophobic, so when it is released into the blood it binds to transport proteins (mainly thyroxine-binding globulin: TBG)

____% of TH that diffuses into the blood is thyroxine (T4)

80%

____% of TH that diffuses into the blood is triiodothyronine (T3)

20

what does TSH do?

binds to and activates the TSH receptor (TSHR), on the surface of thyroid follicular cells

how does TSH stimulate thyroid hormone secretion?

enhances iodide uptake, thyroglobulin synthesis, and thyroperoxidase activity

where does tyrosine come from?

thyroglobulin (Tg); a tyrosine-rich protein synthesized by thyroid follicular cells

MIT

monoiodotyrosine; one iodine molecule attached to a tyrosine in thyroglobulin

DIT

diiodotyrosine; 2 iodine molecules attached to a tyrosine in thyroglobulin

what is iodination?

when thyroperoxidase add iodine molecules to the tyrosine molecules of the thyroglobulin protein

what is conjugation?

process where MITs and DITs mix; can form T3 or T4

how does trioodothyronine (T3) form?

forms when an MIT mixes with a DIT

how does tetraiodothyonine (T4) form?

when two DITs join together

other names for thyroperoxidase

thyroid peroxidase; TPO

T or F: hormones remain anchored to thyroglobulin in the follicles and wait for stimulation by TSH

T

functions of thyroperoxidase

-iodide oxidation
-thyroglobulin iodination
-MIT and DIT coupling

what kind of receptor is the thyroid hormone receptor (TR)?

nuclear receptor; it is in the nucleus

T3 is the active/inactive form of TH

active

T4 is the active/inactive form of TH

inactive

what enzymes convert T4 into T3?

deiodinases 1 and 2 (D1 and D2)

what does deiodinase 3 (D3) do?

inactivates TH (T3 and T4)

what does the thyroid hormone transporter do?

transports T4 and T3 from the blood into the nucleus of cells

what is the amino acid precursor for the synthesis of thyroid hormones?

tyrosine

what is the main transport (carrier) protein of Th in blood?

thyroxine-binding globulin (TBG)

what is one example of a reaction that the enzyme thyroperoxidase catalyzes?

thyroglobulin iodination

in peripheral tissues, T4 is converted to T3 by _____ or _____

D1 or D2

what is the element and protein needed for the synthesis of TH?

iodine thyroglobulin

which transporter is responsible for the transport of iodine into the thyroid cells against the concentration gradient?

Na+ I- symport

physiological effect of TH on metabolism

increases basal metabolic rate (the amount of energy that is expended at rest)

physiological effect of TH on temperature

increased heat production (calorigenic effect)

how does TH influence other hormones?

TH has a permissive effect on catecholamines; there is an increase in beta receptors which causes an increase in HR, stroke volume, cardiac output, and contractility

TH effect on respiratory centers

increase oxygenation; this ensures adequate blood and oxygen supply to meet the increased metabolic demand

what is a consequence of increased temperature after TH secretion?

increased gene expression of Na+ and K+ ATPase; this leads to increased oxygen consumption, respiration rate, and body temp

TH affects on body organ systems

what are the 2 most common thyroid disorders?

hypothyroidism and hyperthyroidism

what is hypothyroidism?

underactive thyroid; not enough thyroid hormone

what is hyperthyroidism?

overactive thyroid; too much thyroid hormone

what results would you expect from a patient with hypothyroidism?

high TSH and low T4

what results would you expect from a patient with hyperthyroidism?

low TSH and high T4

_______ should be the first test to be performed on any patient with suspected thyroid disfunction

TSH

what does primary hypothyroidism and hyperthyroidism indicate?

the dysfunction is at the level of the thyroid gland

what does secondary hypothyroidism and hyperthyroidism indicate?

the dysfunction is at the level of the hypothalamus or the pituitary gland

what are the two main causes of thyroid disorders

-from birth (e.g. congenital hypothyroidism)
-acquired

how are infants tested for thyroid disorder?

blood spot screening

types of acquired thyroid diseases -autoimmune

-Hashimoto's disease
-toxic goiter (Graves disease)

what is Hashimoto's disease?

hypothyroidism; formation of antithyroid antibodies that attack the thyroid tissue and destroy thyorid cells; most common antibody is anti-TPO (and also anti-Tg); this condition is most often seen in middle-aged women

what is toxic goiter (Graves disease)?

hyperthyroidism; antibodies act like TSH and overstimulate the thyroid

types of acquired thyroid diseases -pituitary

problems in the pituitary gland (like tumors) can cause thyroid disorders

types of acquired thyroid diseases - nodules

growth of abnormal tissue

types of acquired thyroid diseases - side effects

side effects of surgery and drugs can cause thyroid disorders

types of acquired thyroid diseases - iodine deficiency

dietary iodine deficiency can cause Goiter; this is an enlarged thyroid gland caused by a lack of thyroid hormone (due to low supply of iodine). This causes excess TSH secretion by the pituitary which enlarges the gland.

function of parathyroid gland

secretes parathyroid hormone (PTH) which regulates calcium level in the blood; directly monitors blood composition and secretes PTH when calcium level dips too low (not regulated by the pituitary)

effects of PTH on bone

-inhibits osteoblasts
-stimulates osteoclasts
-bone is broken down, releasing calcium ions into bloodstream (calcium resorption)

structure of parathyroid gland

4 ovoid glands (some people can have more), partially embedded in the posterior surface of the thyroid

effects of PTH on kidneys

-PTH stimulates kidney tubule cells to recover waste calcium from the urine (decrease calcium loss from urine)
-PTH stimulates kidney tubule cells to release calcitriol

what structures make up the adrenal gland?

the adrenal cortex (superficial) and the adrenal medulla (deep)

what are the 3 zones of the adrenal cortex (from superficial to deep)?

-zona glomerulosa
-zona fasciculata
-zona reticularis

what steroid hormone does the zona glomerulosa produce?

mineralcorticoids (Aldosterone)

what steroid hormone does the zona fasciculata produce?

glucocorticoids (cortisol)

what steroid hormone does the zona reticularis produce?

androgens (mostly DHEA)

which steroid hormones are known as corticosteroids?

mineralcorticoids (Aldosterone) and glucocorticoids (Cortisol)

what do androgens (mostly DHEA) require to activate sex steroids?

peripheral conversion

chromaffin cells

sympathetic postganglionic neurons, without dendrites or axons; these are neuroendocrine cells; they release epinephrine and noepinephrine (catecholamines); found in adrenal medulla

what is a benign tumor of the chromaffin cells in the adrenal gland called?

pheochromocytoma; continuously overproduces catecholamines

adrenal medulla function

releases hormones into the bloodstream; produces 3/4 epinephrine, 1/4 noepinephrine, and dopamine

main function of aldosterone

stimulates kidneys to retain sodium; water is retained with it by osmosis; this increases the circulating volume and therefore increases BP

main function of cortisol

it is the major glucocorticoid and increases in response to stress; it suppresses the immune system (basis for immunosuppressive drug therapy with glucocorticoids)

effects of cortisol on metabolism

-increases protein catabolism by breaking amino acids into glucose
-increases gluconeogenesis (process that transforms non carbohydrate substances into glucose)
-decreases glucose uptake (peripheral)
-increases fat deposition (increased abdominal fat and lipolysis in peripheral fat)
*all of these effects contribute to hyperglycemia

main function of zona glomerulosa

aldosterone retains sodium; SALT

main function of zona fasciculata

produces cortisol which causes glucose release into bloodstream and can lead to hyperglycemia; SUGAR

main function of zona reticularis

produces androgens; SEX

3 steps in cortisol production

1. hypothalamus secretes CRH
2. pituitary gland produces ACTH
3. adrenal gland produces cortisol

_________ regulates both adrenal androgen and cortisol secretion

ACTH

functions of DHEA - fetus

prenatal development of male reproductive tract

functions of DHEA - at puberty

increased growth of pubic and axillary hair and their associated apocrine sweat glands (in both sexes)

____________ occurs years before ___________

adrenarche; gonadarche

what is adrenarche?

secretion of adrenal androgens

what is gonadarche?

secretion of gonadal sex steroids

T or F: Adrenal androgens seem to play a major role in the fully androgenized adult man

F: Adrenal androgens don't seem to play a major role in the fully androgenized adult man

what are the main adrenal androgens

dehydroepiandrosterone (DHEA) and DHEAS (which have low biological activity); these are converted to their more potent forms testosterone and dihydrotestosterone

virilization

excessive adrenal androgens production in women; causes them to develop masculine physical traits

estradiol

the main adrenal estrogen; plays a role after menopause because the ovaries no longer function to produce estrogen so only the adrenals secrete estrogen

Conn's syndrome (primary hyper aldosteronism)

caused by hypersecretion of the adrenocortical hormone aldosterone; increases BP because more sodium and water are retained in the body

secondary hyper aldosteronism

caused by hypersecretion of the adrenocortical hormone aldosterone