Endocrine System (Part 2)

Thyroid hormone

Thyroid hormone

body's major metabolic hormone; composed of 2 hormones containing iodine; binds to intracellular receptors

2 components of thyroid hormone

thyroxine and triiodothyronine

Thyroxine (T4)

major product secreted by thyroid follicles; has 4 iodines

Triiodothyronine (T3)

most will be formed at the target tissue by conversion from T4; has 3 iodines

Thyroid gland

only endocrine gland that stores hormone extracellularly and keeps ~2-3 months of hormone available

synthesis of thyroid hormone

process starts when TSH from anterior pituitary binds to receptors on thyroid follicular cells; as T3 and T4 are released, colloid restocking begins

Metabolism

All of the chemical reactions that occur within an organism

Calcitonin

the "other" thyroid hormone; made by parafollicular cells of the thyroid gland; no well-established physiological role in humans

Calcitonin in non-human animals

released in response to a rise in blood Ca2+, opposing the effects of parathyroid hormone (PTH)

If you have thyroid gland removed

don't need to medically replace calcitonin, but must replace thyroid hormone

Calcitonin as a pharmacological entity

given to treat Paget's Disease and in some circumstances osteoporosis; inhibits osteoclasts????; can stimulate uptake of Ca2+ into bone; in other animals, briefly reduces Ca2+ in blood

Parathyroid glands

small set of jelly bean-shaped glands associated with the thyroid; produce parathyroid hormone

Parathyroid hormone

released when blood calcium is low; increases calcium in the blood

hypocalcemia

low blood calcium

Mechanisms by which parathyroid hormone increases blood calcium

increase osteoclast activity to break down osseous material and release Ca2+; increase Ca2+ reabsorption in kidney tubule; increase activation of vitamin D by kidney --> increase Ca2+ absorption from food in small intestine

adrenal glands (suprarenal glands)

sit on top of the kidneys; adrenal glands are enclosed by a protective fibrous capsule and fat 'cushion'; 2 sections: medulla and cortex both produce hormones

oxyphil cells of parathyroid

we don't know what they do! science is HUMAN

Adrenal medulla

inner-most structures; less like glandular tissue and more like a collection of nervous tissue; part of the sympathetic nervous system

adrenal cortex

outer-most, superior layer; encapsulates the medulla; proper glandular tissue

3 layers of the adrenal cortex (superficial to deep)

zona glomerulosa, zona fasciculata, zona reticularis

Adrenal cortex hormones

produces over 2 dozen known steroid hormones (building block is cholesterol); cortical region of adrenal glands is very lipid-rich

Mineralocorticoids

hormones (ex: aldosterone) that control balance of minerals and H2O

glucocorticoids

metabolic hormones (gluco - sugar), help to keep blood glucose levels fairly constant

gonadocorticoids

adrenal sex hormones

zona glomerulosa, zona fasciculata, zona reticularis

3 layers of cortex, superficial to deep

zona glomerulosa

most superficial layer of cortex beneath capsule, produces mineralocorticoids (e.g. aldosterone)

zona fasciculata

middle layer of cortex, cells are organized into distinctive linear cords, produces glucocorticoids

zona reticularis

innermost layer, sits adjacent to adrenal medulla, produces small amounts of gonadocorticoids

Aldosterone

regulates electrolytes (specifically Na+ and K+) in extracellular fluids, comprises ~95% of all mineralocorticoids

aldosterone effects on Na+

single most abundant cation in ECF; amount of Na+ determines ECF volume; changes in Na+ with change both blood volume and pressure; regulation of Na+ alters levels/activity of other ions (K+, H+, HCO3-, Cl-)

Na+/K+ relative levels

key to resting membrane potential, very carefully controlled levels, related to kidneys

Aldosterone effects on K+

sets resting membrane potential!!; Determines how easily action potentials are generated

CRH

corticotropin releasing hormone

inhibitory effects of aldosterone

blocks the renin/angiotensin pathway - blood pressure drops

aldosterone functions on kidney

cells of juxtaglomerular complex are activated and make renin; renin cleaves a protein (angiotensinogen) to produce angiotensin II

gluconeogenesis

synthesis of glucose from lactic acid and non-carbohydrate sources; making glucose from fats & proteins; energy metabolism

cortisol, corticosterone, cortisone

3 types of glucocorticoids

cortisol

aka hydrocortisone, main glucocorticoid produced in humans

cyclic daily pattern of glucocorticoids

spikes before waking up, drops before and shortly after falling asleep, acute stress disturbs pattern and levels and can drive an increase in blood sugar levels

weak androgens

male sex hormones, converted to testosterone at target tissue cells, small amounts will get converted to estrogen; Amounts made are insignificant compared to what is made by the gonads

androstenedione and dehydroepiandrosterone (DHEA)

two main types of gonadocorticoids

Role of adrenal sex hormones is not clear but in women seems to play a role in

development of axillary (armpit) and pubic hair, sex drive, most of the estrogen made after menopause

Epinephrine and norepinephrine

Two main products of adrenal medulla

Adrenal medulla hormones

Produces two main products (catecholamines made in chromaffin cells), epinephrine & norepinephrine, released during fight-or-flight response but everyday hormones, both molecules has similar effects

epinephrine

~80% of catecholamine release

Pineal gland location

hangs from the roof of the third ventricle in the diencephalon

pineal gland function

secretes melatonin

Pinealocytes

make melatonin

brain sand (pineal sand)

between pinealocytes, dense, Ca2+-containing salts; radiopaque: pineal gland is very obvious on an X-ray of the brain

Pancreas, gonads, placenta

Endocrine Glands that Also Have Other Functions

Adipose Tissue, GI tract, heart, kidneys, skeleton, skin, thymus

Hormone-Secreting Cells in Other Organs

Adipose tissue

can be very metabolically active, not dull or inactive

Pancreas

accessory organ to digestion, has both endocrine and exocrine gland cells

Acinar cells and pancreatic islet cells

endocrine active cell types

Endocrine

dump hormones directly into body fluids (do not have ducts)

exocrine

gland that secretes its products through ducts or channels

Acinar cells

digestive function, make up most of the gland, produce pancreatic juice that is carried to the small intestine via ducts (exocrine)

Pancreatic islet cells (islets of langerhans)

two types: alpha cells and beta cells, together act as sensors to help balance blood sugar levels

alpha cells

glucagon producing, hyperglycemic (increase blood sugar)

beta cells

insulin producing, hypoglycemic (decrease blood sugar)

Glucagon

extremely potent hyperglycemic, one glucagon molecule can lead to the release of 100 million glucose molecules

Major target of glucagon

liver cells

major actions of glucagon

conversion of glycogen -> glucose (glycogenolysis); synthesis of glucose from lactic acid and non-carbohydrate sources (gluconeogenesis); release of glucose to blood

glycogenolysis

breakdown of glycogen to glucose

Insulin regulation and activity

hypoglycemic, two linked amino acid chains, proinsulin: cleaved to produce functional form, also influences metabolism of fats and protein, important roles in brain development (brain is a MAJOR user of sugar)

insulin lowers blood glucose in 3 ways

1. increases transport of glucose and other sugars into cells

2. inhibits glycogen -> glucose conversion

3. inhibits amino acid or fat -> glucose conversion

ovaries

female gonads, release ova and produce estrogens and progesterone

estrogens

maturation of reproductive organs, development of secondary sex characteristics (collection of 3 hormones)

progesterone (working with estrogen)

breast development and changes in uterine mucosa

Testes

male gonads, main hormone: testosterone

testosterone

maturation of the reproductive organs, development of secondary sex characteristics, normal sperm production

Placenta

temporary endocrine organ (short and sweet); Makes estrogen and progesterone and human chorionic gonadotropin

gigantism

excessive height, caused by too much growth hormone in childhood

acromegaly

too much GH after epiphyseal plates have closed, overgrowth of bone in face and extremities

dwarfism

too little GH in childhood; if detected early, can be treated with GH

hypothyroidism (myxedema)

lowers the metabolic rate

hyperthyroidism

Most common form: Grave's Disease; Autoimmune disorder; increases metabolic rate; symptoms: sweating, irregular heartbeat, weight loss, protruding eyes

diabetes

emerging health crisis, becoming more common

Type I diabetes

aka: insulin-dependent, juvenile; generally diagnosed before 15 years of age; autoimmune disease; body attacks its beta cells; several susceptibility genes have been ID'd; molecular mimicry: viral infection looks so similar to beta cells that virus and cells are attacked

Treatment for Type I diabetes

insulin via injection or pump; difficult to control sugar levels; no 'artificial pancreas' exists

Type II diabetes

non-insulin dependent or adult-onset; insulin is produced but insulin receptors can't respond; insulin resistance; incidence increases with age and obesity; ~12 million Type II diabetics in the US

Causes of type II diabetes

Genetics: 25-30% of all cases; lifestyle

Gestational diabetes

high blood sugar levels that develop during pregnancy; pregnancy/placental hormones may interfere with insulin binding to insulin receptor (typically temporary)

Risks of gestational diabetes

pre-eclampsia, depression, baby of large size, underdeveloped newborn lungs

Diabetes statistics

100M people in US are diabetic (~325M people in US), two of every 5 people are expected to develop a form of diabetes in their lifetime