ENDO 1

what are the two body regulatory systems

nervous and endocrine

endocrine

autocrine

paracine

endocrine -hormone released in bloodstream

autocrine -hormone released in extracellular fluid and acts on same cell that secreted it

paracine -released tissue and acts within organ of production

which two hormones effect almost all cells

GH and thyroid

different types of cells can secrete the same horomone (T/F)

T

ex. somatostatin :(intestine to slow digestion and reduce acid, pancreas to inhibit B and a cells, and hypothalamus to inhibit pituitary from GH secretion)

5 main amine hormones

T4, T3, adrenaline (epinephrine), noradrenaline (norepinephrine), melatonin

what hormoes does thyroid secrete?

T4, T3 (amines with iodine) and calcitonin (peptide with no iodine)

what hormones secreted by adrenal medulla?

adrenaline and noradrenaline (both neurotransmitters and hormones)

what hormone is produced by pineal gland?

melatonin

what is melatonin synthesized from?

5-HT (5-hydroxytryptophan)

where are peptide/protein hormones made? what are they initially made as, what are they cleaved into?

on ER ribosomes in endocrine glad- initially made as preprohormones, then cleaved to prohormones.

prohormones are then secreted by _________ and cleaved to _________+__________

golgi vesicles, final hormone(s) + peptide(s)

two hormones can come from the same prohormone (T/F)

T

ex. ACTH (adrenocorticotropic hormone) and MSH (melanocyte stim hormone) are cleaved from the same prohormone (implications in addisons disease discussed later)

peptide hormones can also be neurotransmitters (T/F)

T

what stimulates exocytosis of a hormone?

an increase of extracellular Ca2+ (can be due to nerve signal, other hormone or other depolarization)

what are all steroid hormones derived from?

cholesterol

(some glands make their own cholesterol, others get it from a plasma lipoprotein from liver)

cholesterol → _______→ _________

cholesterol→ pregnenolone → progesterone

where is progesterone secreted?

corpus luteum of ovary (structure formed after egg release)

(in testes) progesterone → __________ → ____________→(in ovaries)→ ________

(in arenals) progesterone→ ___________

(in testes) progesterone→ andosterone→testosterone →(in ovaries)→ estradiol-17B

(in adrenals) progesterone→cortisol (hydrocortisone)

soluble hormones (adrenaline, noradrenaline, peptides) move through blood how?

insoluble hormones (steroid, thyroid) move through blood how?

freely in dissolved state

attached to carrier proteins (often HSA-human serum albumin)

protein hormones are secreted as heterodimeric isoforms with N glycosilation sites. what are main ooligosaccharides added in glycosylation?

sialic acid carbs (sialation)- mostly, and sulphated carbs (sulphanation)

how are glycoproteins inactivated?

deglycosilation and proteolysis

deglycosilation and proteolysis of protein horomones occurs how?

plasma glycosidases- remove sialic acid

hepatic cells- recognize exposed bonds and destroy

more acidic proteins last longer (T/F)

T

more acidic/ more glycosylated proteins have a longer half life in circulation

why do peptide/ protein hormones secrete in bursts?

to ensure that tissue sensitivity to them is not lost

types of rhythyms of release

circadian (24hr)

eposodic (pulsatile)

phasic (surge)

4 inputs that control secretion of endocirne cells

change in plasma mineral concentrations

change in plasma organic nutrient concentrations

neurotransmitters released act on cell

hormones released act on cell

hormone receptor proteins are :______, _______ and _______

specific, high affinity, and low capacity (saturable)

more receptors = (more/less) sensitive tissue rxn

more

hormones with PM receptor-

hormones with cyt→nuclear receptor-

hormones with nuclear receptor-

hormones with PM receptor- peptide, catacholamine

hormones with cyt→nuclear receptor- steroid

hormones with nuclear receptor- T3, T4

what are the two parts of the pituitary gland (hypophysis) - give both names for each part

anterior (adenohypophysis)- glandular (pars distalis and pars tuberalis)

posterior (neurohypophysis)- nervous tissue (pars nervosa)

what part of the pituitary is not found in adults?

pars intermedialis

what connect sthe pituitary gland to the hypothalamus (three names of structure)

pit stalk/hypophyseal stalk/infundibulum

what are the 6 hormones released by the anterior pituitary gland?

GH

ACTH

TSH

prolactin

FSH

LH

describe target and function of each ant-pit hormone:

GH

ACTH

TSH

prolactin

FSH

LH

GH- most tissues- inc growth and protein synth

ACTH- adrenal cortex- inc glucocorticorid secretion

TSH- thyroid- inc thyroid hormone secretion

prolactin- mammary glands- inc milk production

FSH- gonads- inc gametes (and estrogen production in F)

LH- gonads- inc sex hormones (ovulation in F and testosterone in M)

what are the horomones secreted by the posterior pit gland?

oxytocin

ADH (vasopressin)

describe target and function of each ant-pit hormone:

oxytocin

ADH (vasopressin)

oxytocin-uterus and mammary gland- inc contaction in parturation and inc milk ejection in lactation

ADH (vasopressin)- kidney-inc water retention

what types of things stimulate the hypothalamus?

pain, olfactory, exciting and depressing thoughts, blood ions, etc…

how does the hypothalamus control the ant and post pit differently?

ant: controlled by hypothalamic horomones and factors (made in hypothalamic neurons) released by median eminence and transported through hypothalamic-hypophyseal portal vessels

post- controlled by hypothalamic nerve signals through hypothalamo-hypophyseal tract

factor vs hormone

a factor is an uncharachterized/ non purified substance that acts as a hormone

3 mainly discussed hypothalamic inhibitory/release factors

TRH

CRH (cortocopin release hormone)

GHRH & GHIH

what does each hypothalamic inhibitory/release factor do to ant pit?

TRH

CRH

GHRH

GHIH (somatostatin)

TRH- causes release of TSH

CRH- causes release of ACTH

GHRH- causes release of GH

GHIH (somatostatin)- inhibits GH release

how does GH act in liver, adipose and muscle?

liver→ IGF1→ cartilidge and bone growth

liver-gluconeogenesis and glycogenolysis

adipose- lipolysis (FA release)

muscle- decreased glucose usage and switch to FA metabolism

GH deficency can occur at any time (T/F)

true, can be congenital, slow onset or rapid onset

anterior pituitary hormone defiecency is often associated with what condition?

dwarfism

what is height of dwarfs, what specific hormone deficency casues small height?

<4’10, GH

when dwarfs have general anterior pituitary deficency, what is another side effect besides small height?

lack of puberty due to low gonadotropic hormones (LH, FSH, prolactin)

what fraction of dwarfs can sexually reproduce?

1/3

giganitsm caused by

excess GH due to tumor or hyperplasia of ant-pit BEFORE bone epiphyses fuse with shaft of long bones

symptoms associated with gigantism

taller, longer limbs, hyperglycemia

why does gigantism cause hyperglycemia, and what percent of people with gigantism also have diabetes mellitus?

GH acts similar to glucagon in that it raises blood sugar, so overproduction of GH overstimulates B cells of pancreas. 10% of people with gigantism have diabeties.

if a tumor forms causing excess GH secretion after long bone epiphyses have fused, what condition develops? what symptoms?

acromegaly, soft tissue and bone thickness increase.

large hands/feet, cranium, hunch back, enlarged tongue, liver and kidney

describe GH effects on protein synthesis, FA mobilization and glucose usage:

protein synthesis- increased AA into cells, increased protein synthesis- over 24-48 hrs increased DNA transcription, decreased cell catabolism of proteins (maybe due to inc FA supply)

FA mobilization- increased FA from adipose used to make acetyl COA so switch from glucose to FA metabolism. excess GH can cause excess fat and acetoacetic acid in liver-ketosis and fatty liver

glucose usage- decreased due to now being on FA metabolism, glucose cannot be used so glucose→glycogen in cells, in 30-60 mins can get hyperglycemia THAT IS NOT RESPONSIVE TO INSULIN THERAPY, and can become an issue burning out B cells and leading to diabetes.

describe generally how long bones grow

GH stimulates cartlidge at epihyseal plates and produces more chondrocytes that can calcify to bone on each end of bone- causing bone to get longer, when cartlidge is used up fusion of shaft and epiphysis occurs and bone can no longer grow

GH stimulates (osteoclasts or osteoblasts) in periosteum and bone cavities

osteoblasts (deposit new bone)

when deposit>removal, bone grows

GH works with _______that it stimulates to be produced in liver

IGF-1 (somatomedian-c)

what does IGF1 do?

works with GH to stimulate growth

chondrocytes secrete and become responsive to IGF1 in differentiation and IGF1 locally stimulates mitosis. IGF1 has _________ functions (autocrine, endocrine, paracrine)

autocrine, paracrine and autocrine

what types of dwarfs cant create IGF1

african pygmy and levi lorain

adult vs child GH levels (ng/mL)

adult- 1.5-3ng/mL

child 6ng/mL

when does GH peak?

early sleep (22:00-02:00)

GH rate can rapidly change (T/F)

T (response to stress, excitement, trauma, exersize)

how do long term nutrient deficencies effect GH levels?

how do childhood nutrient deficiencies effect IGF1 levels?

inc GH

dec IGF1 even if GH normal

what hypothalamic hormones regulate GH secretion of ant-pit?

GHRH

GHIH (somatostatin)

region of hypothalamus that controls GHIH or GHRH secretion also responds to blood glucose levels- what does this imply?

signals that initiate feeding may also stimulate GH secretion

in thyroid regulation:

hypothalamus secretes ______ to ant pit

ant pit secrets _______ which stimulates thyroid

TRH, TSH

follicular epithelial cells in thyroid gland (thyrocytes) create assemble in rings to form follicles, and secrete ______ into follicular space

colloid

what is colloid?

mostly made of glycoprotein thyroglobulin

thyroglobulin is rich in what AA?

what purpose does this serve?

Tyr (~70)

serve as site for iodine to bind and create thyroid hormones

iodine in food is absorbed by intestine in to blood and is then ionized into _______ which moves to thyroid

iodide

what is the process of accumulating iodide in folicular epithelial cells called?

iodide trapping (cell conc can be 30x blood conc)

explain the process of thyroglobulin organification in follicular epithelial cells

iodide oxidized by peroxidase to iodine

iodine attaches to tyrosine of thyroglobulin facillitated by iodinase

where is peroxidase enzyme found?

follicular cell apical border where thyroglobulin enters folicle

MIT and DIT and what they produce

MIT- monoiodotyrosine, DIT-diiodotyrosine

MIT+DIT= T3

DIT+DIT= T4

is T3 or T4 secreted in larger amounts?

80% of throid hormone secreted is T4

is T3 or T4 used in cells?

T3 (mostly)

each thyroglobulin molecule stores __ T4 and _ T3

30 T4 and 3 T3

how much of a supply of thyroid hormone do you have stored at a time?

several months

thyroid hormones are lipophillic, how are they moved in plasma?

plasma carrier proteins

thyroid hormones (increase or decrease) growth and metabolism

increase

what hormone is most important regulator of metabolism (basal metabolic rate)

T3 and T4

calcitonin works in body to do what?

increase bone desposition (decrease blood Ca2+) in young- little adult effect

calcitonin effects are oppisite that of ____

PTH

hyperthyroidism symptoms

heat intolerance, weight loss, weakness, neurosis, fatigue, low sleep, tremor, exophthalmia (protruding eyes), enlarged thyroid

• graves disease, thyrocotoxicosis, toxic goitre

hypothyroid symptoms

tired even when sleeping excessively, weakness, slow HR, low cardiac output, low blood volume, increased weight, constipation, mental decline, low hair growth, dry skin and voice, edema in throat (myxedema), atherosclerosis (due to increased cholesterol-liver met too slow)

thyroid disease are autoimmune diseases (T/F)

T

how would you differentiate hyperthyroid vs excessive TSH production

hyperthyroid usually has low-no TSH in bloodstream due to negative feedback, rather hyperthyroid is caused by antibodies that mimic TSH, or occasionally due to a tumor of the thyroid gland (normal cells respond to neg feedback and stop secreting, but tumor cells do not)

explain the two main causes of hypothyroidism

1. autoimmune disease where antibodies destroy thryroid gland (small thryroid)

2. iodine deficency preventing T4 and T3 production, but thyroglobuin is still released and TSH not inhibited (no neg feedback) (enlarged thyroid)

thyroid (increases/decreases)

met rate, endocrine activity, mental activity

number and size of mitochondria in cell

Na+K+-ATPase

protein use and production

increases

what can be caused due to lack of iodine (low thyroid production) in fetus/infant?

mental impairment- cretinism

hypothyroid effect on growth

hyperthyroid effect on growth

decreased growth

excess growth but early closure of epiphyses so lower overal height

why is thyroid # determinant of metabolic rate

influences enzyme/protein synthesis

thyroid effect on:

carb metabolism

adipocytes

vitimins

oxygen requirement

HR

carb metabolism- inc glucose uptake, gluconeogenesis, absorption in gut and insulin secretion

adipocytes- releases free FA and accelerates B oxidation of free FA

vitimins- increased need for vitimins

oxygen requirement- increased O2 requiement (vasodialation, inc blood flow, thermoregulation

HR- increased HR and force

how does hyperthyroidism effect heart

actually depresses heart muscle due to excess protein catabolism causing nervousness, exhaustion and anxiety

why does thyroid reduce cholesterol, phospholipid and triglycerides in plasma?

increases cholesterol secretion in bile by increasing LDL receptors on liver

an increased metabolic rate can lead to weight loss but often doesnt, why?

increased appetite

explain effects of hypo an dhyper thyroid on male vs female

male

hypo- low libido

hyper- impotence

female

hypo- mennorhagia, polymennorhea, amenorrhea

hyper- oligiomennorhea , amennorhea

4 ways in which TSH increases T3 and T4 secretion by thyroid

1. increase thyroglobin proteolysis

2. increase iodine trapping in glandular cells

3. increase iodination of tyrosine ad coupling to form thyroid hormones

4. increase size, number and activity of thyroid cells

cold exposure (inc/dec) thyroid production, why?

increase (higher met rate to warm up)

when T3 and T4 are released, negative feedback tells the hypothal to stop secreting TRH and also provides feedback to the ant pit to _____

reduce number of TRH receptors on TSH releasing cells

vasopressin (ADH) regulates water expression in kidney by increasing ________ permeability so more water is reabsorbed

collecting duct