Adrenal medulla

"independent" endocrine gland, NOT part of the HPTO axis

produces epinephrine, norepinephrine

Adrenal gland blood supply

abdominal aorta-->vena cava

glomerulosa

outermost layer of adrenal cortex

produces aldosterone

fasciculata

middle layer of adrenal cortex

produces cortisol

reticularis

innermost layer of adrenal cortex

produces androgens

structural relationship between aldosterone and cortisol

so similar that can bind (relatively weakly) to each other's receptors

physiological impact

parallel pathways of steroid hormone synthesis

there are multiple paths to the synthesis of each steroid hormone, dependent on MANY different enzymes

ACTH

adrenocorticotropic hormone

released from ant pituitary stimulated by CRF(corticotropin-releasing factor) from hypothalamus

acts on adrenal cortex, stimulates release of cortisol and stimulates production of enzymes needed for steroidogenesis (in zona fasiculata)

ACTH trophic effects

stimulates cell growth/proliferation in adrenal cortex

deficiency-->reduce in hormone production, atrophy of adrenal cortex (-->affects aldosterone)

neg feedback of cortisol (3 places)

ACTH-->neg feedback on hypothalamus

cortisol-->hypothalamus and ant pit

Diurnal rhythm of cortisol driven by mechanism in hypothalamus

Actions of cortisol

modulate inflammatory/immune response

stress response

counter-regulates insulin, maintains blood glucose level

mineralocorticoid effects in high conc (salt/water balances)

stimulus for release of aldosterone

increase in plasma [K⁺] & increase in angiotensin II (low [Na+] and low blood volume)

actions of aldosterone

alters number and activity of Na and K transport proteins in cell memb

kidney: aldosterone-->increase in Na⁺ resorption and loss of K⁺

at very high conc, can mimic cortisol actions (can bind to cortisol receptors)

cortisol inhibitors

no direct inhibitors

cortisol transport

cortisol-binding globulin (CBG) aka transcortin transports cortisol in bloodstream

lack of cortisol

death

cortisol and muscle

maintain muscle function, dec muscle mass

cortisol and bone

decrease bone formation, inc resorption

cortisol and connective tissue

decrease connective tissue

cortisol and brain

modulate emotional tone, wakefulness

cortisol and kidney

increase glomerular filtration and free water clearance

cortisol and fetus

facilitates maturation of fetus

cortisol and immune system

inhibits inflammation and immune response

cortisol and CV system

maintain cardiac output, inc arteriolar tone, decrease endothelial permeability

Cushing's syndrome

hypercortisol secretion:

central obesity, fatigue, hypertension, hirsutism (excessive hair), menstrual irregularity, depression, muscle wasting, edema, bone thinning, glucose intolerance, thinning of skin

adrenal insufficiency

*aldosterone and adrenal androgens also dec

weakeness, hyperpigmentation of skin, weight loss, anorexia/nausea/vomiting, hypotension (orthostatic), salt craving, syncope (fainting)

aldosterone inhibitor

Atrial netriuretic protein (ANP)

aldosterone transport

bound to plasma proteins (minimal)--aldosterone-binding globulin (ABG), most transported in solution

aldosterone removal

liver degrades, kidneys excrete

half-life=20 min

aldosterone mechanism of action

enters nucleus, alters gene transcription

also has extra-nuclear (non-genomic) effects via activation of second messengers

hyperaldosterone

centripetal obesity, fatigue, hypertension, hirsutism, amenorrhea, personality changes, peripheral myopathy, edema, Na retention, K/H loss, water retention, alkalosis

hypoaldosterone secretion

weakness, hyperpigmentation of skin, weight loss, anorexia/nausea/vom, hypotension, salt craving, syncope, dec blood vol, hyperkalemia (hi K levels), acidosis

chromaffin cells

adrenal medulla cells synth and secrete catecholamine hormone, innervated by sympathetic nervous system

adrenal medulla hormones

catecholamine, epinephrine, norepinephrine

tyrosine precursor

final enzyme (PNMT) promoted by cortisol

catecholamine actions

reg of blood glucose conc

act on sites innervated by sympathetic portion of autonomic nervous system

catecholamine release stimulus

stimulation of sympathetic pre-gangionic neurons

catecholamine inhibitors

no direct inhibitors

catecholamine blood transport

free in solution, some bound to albumin

catecholamine removal

Epi: metab'd by MOA

Norepi: metab'd by COMPT

excreted by kidney

1/2 life very short

catecholamine mechanism of action

bind to adrenergic receptors in cell memb

hypersecretion of epi/norepinephrine

pheochromocytoma--adrenal gland tumor

sustained hypertension, sweating, palpitations, hyperglycemia, glucosuria

hyposecretion of epinephrine

secondary to lack of cortisol, and therefore reduced PNMT

orthostatic hypertension

where thyroid hormone is produced

follicular cells, simple cuboidal epithelium in spherical form filled with colloid

hormones released by thyroid gland follicular cells

thyroxine and triiodothyronine (T3/T4), tyrosine derivatives

synthesis of T3/T4

requires uptake of iodine (I^-) by NIS transporter (sodium-iodine symporter)

Na⁺ enters cell down conc grad, and I^- enters against

dependent on Na-K ATPase to maintain Na⁺ gradient

NIS transporter-->30:1 conc gradient for iodide

T3

biologically active form of TH

some T4 is converted to T3 in peripheral tissues (liver and kidneys)

stimulus for release of TH

TSH Thyroid-Stimulating Hormone

inhibitors of TH release

none

TH transport in blood

not water soluble

plasma proteins:

70% thyroid-binding globulin (TBG)

30% transerythrin

.03% T4 in solution

.3% T3 in solution

TH removal

by liver, kidneys, and skeletal muscle

half life T4: 6-7 days

half life T3: 18 hrs

TH mechanism of action

enters cell by energy-dependent process, enters nucleus where it alters gene transcription-->enzyme levels

TH action

affects growth

controls basal metabolic rate

interacts with (reinforces) activity of sympathetics

TSH originates from:

HPTO axis

TH inhibits/stimulates:

 inhibits: TSH and TRH release

stimulates: hypothalamic release of somatostatin (which inhibits TSH release)

long loop feedback ONLY (TSH does not inhibit hypothalamus)

Aside from controlling TH synthesis, TSH also:

controls growth of thyroid cells and thyroid gland

T4-->T3 conversion

de-iodination

T4 in cell:

NOT biologically active, must be converted to T3 after uptake by the cell

TH hypersecretion

CNS hyperexcitability

heat intolerance

increased sweating

weight loss

diarrhea

muscle weakness

fatigue

lack of sleep

tremor