PGY 206 Exam 2 ENDOCRINE UKY

What are hormones?

chemical messengers secreted by the ductless endocrine glands

Where do endocrine hormones travel?

in the blood to reach and communicate with target cells

Comparison of bodies 2 two communication systems

The nervous system: POINT TO POINT and min- to-min rapid but short- lived controls. Neurotransmitters

The endocrine system: BROADCASTNG ( blood vessels reaching every corner of the body) and slow but sustained controls. Hormones

what determines hormone effect?

hormone concentration in plasma

Hydrophilic polar hormones

a) Catecholamine hormones

b) Peptide/protein hormones

Stored, travel free of proteins in plasma

bind and activate their specific trans-membrane (integral) receptor

Hydrophobic non-polar hormones

a) Thyroid hormones

b) Steroid hormones

c) vitamin D

Made on demand/Not stored

a lot are associated with proteins

Catecholamine Hormones

Circulate freely with short half-life

Secreted by neurons and adrenal medulla:

epinephrine, norepinephrine, dopamine to bind GPCRs

Synthesized via enzymatic reactions, from amino acid tyrosine.

Rate limiting enzyme: Tyrosine Hydroxylase

peptide and protein hormones

Circulate freely with short half-life

Synthesized through transcription, translation

Stored in secretory vesicles & secreted in response to stimuli

Examples: Insulin, Prolactin

Peptide and protein hormone targets

A.) GPCRs: Glucogon-R, ACTH-R

B.) Receptors with intrinsic kinase activity: Tyrosine kinase R, IGF-1-R, Insulin-R

C.)JAK Kinase associated receptors: GH-R, Leptin-R PRL-R

thyroid hormones

T3 & T4

-synthesis involves enzymatic incorporation of iodide onto tyrosine

-not stored, made on demand

-bind intracellular receptors, ligand-induced transcription factors

-slow cellular response involving changes at transcription-translation

-metabolized for increased solubility and excreted

Steroid Hormones

-synthesis involves enzymatic reactions from cholesterol. P450 is rate limiting enzyme

-secreted by ovaries, testes, adrenal glands

-not stored, made on demand

-bind intracellular receptors, ligand-induced transcription factors

-slow cellular response involving changes at transcription-translation

-metabolized for increased solubility and excreted

Vitamin D

-synthesis involves enzymatic activation to 1,25-dihydroxy-vitamin D

-not stored, made on demand

-bind intracellular receptors, ligand-induced transcription factors

-slow cellular response involving changes at transcription-translation

-metabolized for increased solubility and excreted

T3 and T4

T3 is the active form, most potent

T4 is pro hormone , most stable and abundant form

HYDROPHOBIC hormones in diff places

IN PLASMA:

bind liver-produced binding globulins, long half-life

IN TARGET:

bind their specific intracellular receptor proteins, hormone-bound receptors bind the specific DNA sequences & alter transcription

IN LIVER:

modified, become hydrophilic & excreted

Max response

related to the

number of functionally available

receptors.

Up-regulation

target cells form more receptors in response to low hormone levels

Down-regulation

target cells lose receptors in response to high hormone levels

Physiological dose vs Pharmacological dose

PHYS: normal/typical concentrations in the body, that leads to normal effects.

PHARM: abnormally high concentrations that leads to abnormal effects that are not observed with

physiological doses.

Sensitivity

[H] that elicits the half-maximal response... the sensitivity is linked to genetics, inhibitors, or activators.

Insensitivity

could be caused by the low number of the receptor or de- sensitized receptors

requiring more [H] for the same response

Hypersensitivity

could be caused by the high number of the receptors or hyper-sensitized receptors

requiring less [H] for the same response

Permissiveness

HormoneA cannot exert its full effects in the absence of hormone B (has no effect by itself)

Catecholeamine pro-hormone example

NE-> E

Norephinepherine to epinephrine

Peptide pro hormone example

A polypeptide hormone

(pro-insulin) -> a shorter hormone (insulin) + a copeptide (C-peptide)

Steroid pro hormone example

testosterone -> estradiol

testosterone -> dihydrotestosterone (DHT)

Thyroid pro-hormone example

Thyroxine T4 -> T3

Vitamin D pro-hormone example

25-(OH)-VitD -> 1,25-(OH)2-vitD

What 3 organs Store and Release Energy Substrates during Fed and Fasting States?

Liver, Skeletal muscles, fat

Carbohydrates

- stored as glycogen in liver & muscle

- about 1 day's needs

glycogenesis: glucose->gycogen

glycogenolysis: glycogen->glucose

*gluconeogenesis: de novo synthesis of glucose

Fats

- stored as triglyceride in adipocytes

- MOST ABUNDANT

- MOST EFFICIENT energy reserve

lipogenesis: FFA and glycerol -> TG (fat)

*lipolysis: TG->FFA + glycerol

ketogenesis: FFA -> ketone

Protein

- stored in muscle

- major source of blood glucose in LONG-FASTING

protein synthesis (proteogenesis): a.a. -> protein

proteolysis: protein -> a.a.

genesis vs lysis

genesis- makine

lysis- breaking down

Genesis generally happens during FED STATE

except for gluconeogenesis and keptgenesis

Lysis generally happens during FASTING STATE

Absorptive phase ( < 4Hs: FED)

High glucose -> High Insulin, Low Glucagon

Promotes ANABOLISM, inhibits CATABOLISM

How does insulin work at the liver ?

Glucose enters the liver through insulin independent transporters, GLUT2 (this happens with or without insulin)

BUT

Insulin ↑ the activity of glucokinase which stimulates glycolysis inside the cell; this helps to maintain the glucose concentration in the liver cells very low, which allows more glucose diffuse in.

How does insulin work at skeletal and fat?

Glucose enters these cells by insulin-dependent glucose transporter 4 (GLUT4)

Insulin stimulates GLUT4 to do this

Post Absorptive phase (>4hrs : FASTING)

Low glucose -> low insulin & high glucagon

CNS cells preferentially use glucose.

Promotes CATABOLISM

Low insulin results in catabolism

LIVER:

glycogen -> glucose

gluconeogenesis and ketogenesis

SKELETAL MUSCLE:

glycogen -> pyruvate & lactic acid

protein -> Amino Acids for long term fasting

FAT TISSUES:

Fat/TG -> glycerol & FFA

diebetes mellitus

Lots of sweet urine

Uncontrolled blood glucose levels

Elevated blood glucose and decreased glucose tolerance

3p symptoms of diabetes

Polyuria- excessive urination

Polydipsia- excessive thirst

Polyphagia- excessive hunger

characterized by hunger, fatigue, and weight loss

Other symptoms of diabetes

some develop fast (associated with insulin deficiency, type I)

others develop slowly (associated with insulin insensitivity, type II)

Type 1 (insulin dependent)

-Autoimmune genetic components

-caused by destruction of beta cells

-Rapid onset

-Triggers: cold weather/viruses

-associated with ketoacidosis

-insulin therapy

Type 2 (insulin independent)

-Majority of diabetes is this type

-Insulin insensitivity

-Strong genetic component, associated with obesity

-often times develop type 1 as well

Why is physical exercise helpful for diabetes ?

induces intracellular signals that increase and thus enhances glucose uptake from

plasma- could alleviate symptoms associated with hyperglycemia. INCREASES BODYS INSULIN SENSITIVITY

Complications of exercise with diabetes

For an individual who relies on an insulin pump, insulin doses should be lowered for when intense excersice is happening

The anterior pituitary gland

-derived from the roof of the mouth- endocrine tissues

-Receives hypothalamic RH & IH

-secretes: FSH, LH, TSH, ACTH, GH, PRL

blood supply from hypothalamic portal vessel

posterior pituitary gland

-derived from the embryonic brain tissues- neural tissues

-secretes ADH and oxytocin which are made in the soma/cell body in the hypothalamus, packaged, transported to the PP and stored in the PP

-blood supply from arterial

Arterial blood supply of pituitary

Posterior Pituitary: YES

Anterior pituitary: NO, receives blood from hypothalamus

Prolonged elevation in an AP hormone

overstimulates the target gland -> enlarges the target gland (hypertrophy)

Prolonged deficiency in an AP hormone

understimulates the target gland -> shrinks the target gland (atrophy)

Ectopic hormones.

hormones produced by tumors of tissues that are not normally engaged in the production of that hormone

Panhypopituitarism

Loss of all anterior pituitary function

Destruction of the gland

blood clots in the portal vessel leading to a total loss of blood supply to the anterior pituitary

Treatment? Lifelong hormone replacement therapy

Kallmann's syndrome

fetal GnRH neurons fail to migrate due to defective KAL-1

no GnRH -> deficiency of LH & FSH -> hypogonadism

Excess of one hormone

Often caused by a pituitary tumor; The pituitary gland is surrounded by bone; Tumors of the gland may compress the retina-hypothalamic track causing headaches and/or impaired vision

Acromegly

Hypersecretion of GH after long bone growth has ended

ADH

stimulates water re-absorption by the kidney

Too little ADH or impaired ADH receptors?

Diabetes insipidus (a lot of urine with no taste)

Oxytocin

stimulates smooth muscle contraction and modulates neuronal activities

Thyroid hormone synthesis requires

iodine supplied in diet

-if radioactive iodine is ingested, you will see more or less selective uptake of radioactive iodide by the thyroid gland.

Thyroid follicular cell

actively takes up Iodide(I-) from plasma->colloid

makes everything necessary for making thyroid hormones

(e.g., enzymes, thyroglobulin etc)->colloid

Colloid

Iodination of tyrosine and coupling of iodinated residues of thyroglobulin -> formation of a large T3:T4:thyroglobulin (T3 & T4 still attached to thyroglobulin)

Thyroid follicle

Hydrolysis of the endocytosed T3:T4:thyroglobulin

Free T3 and T4 -> diffuse to plasma -> bind to carrier proteins

Free T3

diffuses into target cells, binds and activates nuclear T3R (TR) for modulating transcription.

3 functions of free T3

a) Increase BMR (calorigenic effects) by stimulating mobilization of energy substrates, O2 consumption, & Na/K ATPase GENERATES HEAT

b) Potentiate sympathetic responses (b-adrenergic responses)

c) Required for complex processes:

neuron development, proper reflexes

Goiter

Happens when chronically stimulated by TSH/TSH like substances when TSH receptors are chronically activated),

HYPERthyroidism

overactivity of the thyroid gland,

SWEATING, FINE TREMOR, TACHYCARDIA

HEAT INTOLERANCE

WEIGHT LOSS

Graves disease -> widened eyes

HYPOthyroidism

underactivity of the thyroid gland caused by iodine deficiency

GROWTH STUNT, BRADYCARDIA

COLD INTOLERANCE

WEIGHT GAIN

Hashimoto's thyroditis: Autoimmune destruction of follicles -> Eventually leading to hypothyroidism

Thyroid storm

a rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis/hypERthyroidism

Myxedema coma

a medical emergency with a high mortality rate, stemming from

severe hypOthyroidism

Parathyroid glands

PTH targets bones and kidneys directly and guts indirectly, in order to maintain plasma calcium levels

Critical for life ( reason for skillful surgeons for thyroidectomy)

This modified amino acid is an example of a catecholamine.

epinephrine

This hormone is derived from cholesterol.

Aldosterone, cortisol

This hormone's receptor leads to the changed production of cAMP

Epinephrine, TSH

This hormone is carried in plasma by liver-produced binding globulins.

Aldosterone, cortisol, thyroid hormone

This hormone is not a steroid but acts on intracellular receptors.

thyroid hormone

This hormone's receptor is a transcription factor.

Aldosterone, cortisol, thyroid hormone

This hormone is hydrophilic and circulates free in plasma

Insulin, Epinephrine, prolactin, TSH

True or False.. An estrogen priming which increases the synthesis of the receptor for progesterone is required for progesterone effects. This is known as additive effects.

F

True or False.. A prolonged presence of a hormone at a high concentration may decrease its receptors in target cells.This is known as down-regulation

T

Compared to a normal subject, a patient with type II diabetes mellitus has lower sensitivity to insulin and requires

more insulin for the same response

The hypothalamic regulatory factor that is NOT a peptide hormone.

DA

The hypothalamic regulatory factor that inhibits growth hormone secretion.

Somatostatin

This hormone is produced by anterior pituitary cells that also produce FSH.

LH

The only pituitary hormone that is under tonic inhibitory control.

PRL

This anti-thirst hormone is a product secreted by a neuron.

ADH

This hormone is secreted from the posterior pituitary in response to suckling.

OXY

True or False.. Oxytocin is produced in the posterior pituitary.

F

True or False.. ADH secretion by the posterior pituitary is stimulated when the ADH neuronal soma in the hypothalamus is stimulated and triggers the generation of action potential.

T

True or False.. Infertilty in the female can originate from dysfunction at the level of the hypothalamus, pituitary, or ovaries.

T

Compared to a normal subject, a patient with cortisol-secreting adrenal tumor would have ___ (higher, lower, similar) levels of plasma ACTH.

lower

The compression of the hypothalamic-pituitary portal vessel would lead to _____ (increase, do not change, decrease) secretion of ACTH.

decrease

The rate-limiting enzyme of the production of any steroid hormone.

P450SCC

The major mineralocorticoid secreted by the adrenal cortex.

aldosterone

The steroid with the greatest effect on increasing blood glucose levels.

cortisol

Autoimmune destruction of the adrenal cortex is the cause of this disease.

Addison's

Primary Cushing's leads to ___ (higher, normal, lower) levels of plasma cortisol and ___(higher, normal, lower) levels of plasma ACTH

Higher, lower

T/F T4 is the chief circulating form of thyroid hormone.

T

T/F T4 is the most active form of thyroid hormone.

F

T/F Both free T3 and T4 are stored in colloid droplets.

F

T/F TSH receptors are steroids.

F

T/F A goiter develops only in the case of hyperthyroidism.

F

T/F A long-term Iodine-deficient diet will cause a goiter.

T