Hormones

Chemical messengers

Hormones can only elicit a response in cells

That have an appropriate receptor for that hromone

Three different classes of hormones

Biogenic amines
Protein/peptide hormones

<100 amino acids

Peptide hormones

>100 amino acids

Protein hormones

Biogenic amines

Epinephrine

Rough Endoplasmic reticulum

Produces pre-hormones

Pre-hormones are cleaved into pro-hormones in the

Golgi apparatus for packaging and further refinement

Prohormones cleaved into active hormones by enymes in the

golgi apparatus or secretory vesicle

Steroid hormones cannot be stored and must be produced on demand because

They can pass through the cell membrane

Steroids are derived from

cholesterol

Steroids are stored within lipid droplets in the cytoplasm

and can be rapidly produced when needed

Steroid hormones cannot be stored and must be produced

on demand

Progesterone, DHEA, androgesterdione

stimulated by ACTH in adrenal cortex, causing cleavage enzyme to break cholesterol into hormones

Aldosterone synthase

final enzyme that converts corticosterone to aldosterone

16 a hydroxygenase

important for converting corticosterone to cortisol

21a hydroxylase

important enzyme

cells have receptors for hormones that act as

a molecular trigger that turns specific functions on or off

Response of target cells can include

opening or closing ion channels
Synthesis of enymes or proteins
Acctivation ro deactivation
secretion of a cellular product
Stimulation of mitosis

Degree of response is not just determined by presence of receptor but also by

Concerntration of hormone,
Number of receptors
Affinity of hormone to the receptor
presence or absence of

Hormone

Sender

Receptor

sites that can trigger response

Upregulation

Increase cell receptors

Downregulation

Decrease receptors

Synergistic hormones

Work together to produce response that may be additive or complementary

Additive effect

2+2+2 = 7 effect

examples of additive hormones

Glucose, epinephrine, cortisol.

All 3 of these together get large dynamic increase in glucose

Complementary

means each hormone produces a different response that is part of a bigger complete picture. Coorperative effects of hirmones required to achieve desired end state

Cortisol

Adrenal glands release during distress during sickness to help you deal with distress

Permissive effect

A hormone enhances the responsiveness of the target cecll to a second hormone or increases the activity of the second hormone

Antagonistic hormones

Have opposing effects on the same tissue

Oxytocin and prolactin

Baby suckles, stimulates oxytocin, oxytocin causes uterine contraction and milk release.

Estrogen stimulates progesterone in endometreum

Endometrial lining increases response to endometrium and increases chances of implantation

Insulin and glucagon

Antagonistic hormones

Somatostain opposes both insulin and glucagon

Helps to maintain normal range

Hormone receptor interactions

How cell communicates with that hormone

Water soluble

Can travel easily in plasma, cannot get across cell membrane easile

Lipid soluble

Easily makes it across cell membrane, struggles in cytoplasm without carrier protien

Lipid soluble hormones have receptors

within cytoplasm or nucleus of target cell that activates genes and protein synthesis directly

Amino acid based hormones are water soluble and have target receptors on

Cell membranes

Amino acid based hormones are usually working with

second messengers

Common second receptors for hormone receptors are

Cyclic AMP (cAMP)
Inositol triphosphate (IP3)
Diacylglycerol (DAG)

Most common signaling pathways are

cAMP and PIP2-Calcium pathways

cAMP signaling pathways involve 3 components of plasma membrane that trigger intracellular cascade

Hormone receptor
G protein
Adenylate cyclase

Hormone binds to receptor

first membrane

Receptor activates g protein and the hormone travels inside cell membrane and binds to adenylate cyclase

adenylate cyclase converts ATP into cAMP and tow inorganic phosphates cAMP=second messenger

Protein kinases are enzymes that phosphorylate proteins(enzymes)

triggers cascade of chemical reactions within cell

PIP2 calcium mechanism

uses GPCR

Activation of Gprotein splits phospholipid into two 2nd messenger

IP3 7 DAG

Like cAMP, DAg activates protein kinase which triggers cascade of reactions

inside the cell

some receptors use cGMP instead of cAMP

still work similaryl

insulin and IGF-1 use

tyosine kinase instead of cAMP

Receptor is an enzyme called

Tyrosine-kinase

Bindinger causes dimerization and autophosphorylation of the receptor which triggers

traslocation of GLUT4

Steroid hormones in serum

attach to carrier proteins because they are insoluble

on arrival at target cell, hormone deteaches from carrier protein

binds to receptor inside the ccell

once inside steroid binds to receptor inside cell and binds to DNA

Thyroxine

Bind of the complex to the DNA initiates transcription of gene with mRNA

need to know second messengers wrk with Gprotein

moving a enyme to allow for message to make it into cell

level in blood reflects

how much it is being secreted

hormones shouldnt accumulate in blood because they are used by target cells and

turned off by negative feedback

half lives for hormones can be

minutes to days

effects of a hormone on target cells are dependent on concentration of hormone and

receptors

secretion of the hormone is triggered by a stimulus after which the plasma levels of the hormone increases

secretion is inhibited by cell change or release of product by target cell. This is negative feedback

endocrine cell, target cell, response

simple negative feedback.
Ca low
PTH increases, liberates ca from bone
ca increases, PTH is turned off

complex negative feedback (most common)

releasing hormone
target gland
Stimulating hormone
Target tissue

secretion by 3 mechanisms

Humoral
neural
Hormonal

Humoral refers to

blood

Glucose, Ca, Na, K

Hormonal control

Most common via releasing hormones via hypthalamic pituitary axis (HPA), and pituitary tropic hormones

tropic means

stimulates another gland to release its hormones

Neural control involes

neuro-endocrine interface

epinephrine would be an example of

neural control

parasympathetic

lots of GI effects

sympathetic

inhibits GI system

HPA

Hypothalamic pituitary axis

HPA REALLY REALLY REALLY

IMPORTANT

HPA typically 3 hormone sequence

Hypothalamus detects stimulus and
secretes a releasing hormone 1
Releasing hormone stimulates anterior pituitary to release a tropic hormone 2
Tropic hormone stimulates target gland which releases a stimulating hormone 3

Thyroid hormone increase

basal metabolic rate and heat production

thyroid hormone regulates

growth and development of tissues

Thyroid hormone

has permissive effects on the action of epi and norepi by upregulating beta reeptors in heart and nervous system

thyroid hormone is actually how many hormones

two, T3 and T4

Most T3 is T4 that is

converted in tissue

Thyroxine aka

T4

Colloid contains

Thyroglobulin

TG

Thyroglobulin

Iodide trapping is the first step in

Thyroid hormone synthesis

Iiodine is co-transported with Na+ into the follicular cells

where it is transported into the colloid by a membrane protein called pendrin

Iodide is oxidized to become I2

then attached to tyrosine

Tyrosine with one iodine is called

Monoiodotyrosine (MIT)

Diodotyrosine aka

DIT

Next the phenolic ring of MIT or DIT is removed from its tyrosine and added to another DIT to produce either

T3 or T4

To secrete thyroid hormone, follicular cells use endocytosis to engulf colloid where T3 and T4 get transported out of the cell

by thyroid binding globulin TBG

TBG vs TG

big deal

When TSH stimulated

secretory granules get really big and produce a lot more colloid

secretory granules are

normally slowly moving a little bit of colloid continuously

Dont care about knowing chemical structures

or isomers

Hypothalamus stimulated by cold temperatures, decreased thyroid hormone or other factors

TRH stimulates release of TSH
q

Adrenal glands play an important role in response to stress

Stress is anything physiologic or psychologic

The hypothalamus activates sympathetic nerves

stimulates adrenal medulla to secrete epi/norepi

If a threat persists for more than 10 mins or so

CRH will be released from hypothalamus which will stimulate ACTH

ACTH will stimulate

adrenal cortex to release cortisol

Cortisol elevates blood sugar by stimulating

gluconeogensis in liver and glucagon secretion from pancreas

Cortisol also stimulates lipolysis in adipose tissue

releasing fatty acids into circulation that can be used to make energy

Takes 20-30 minutes

for the body to recover from stressor

General adaptation syndrome 3 stages

Alarm stage Hypothalamic pituitary adrenal axis
Reistance: parasympathetic response cortisol and glucose are still evelated
Exhaustion: immune supression overall deterioration

cortisol is major negative feedback molecule

by telling hypothalamus to knock it off

female Gonadotropins

GnRH to pituitary

LH
FSH to ovaries

(inhibin and estrogen negative feedback on pituitary)

male gonadotropin

GnRH to pituitary

Pituitary to testes
LH
FSH

(inhibin negative feedback on pituitary) (testosterone negative feedback on hypothalamus)

Growth hormone

Growth hormone releasing hormone to pituitary
Pituitary growth hormone to liver cells

Liver cells IGF I negative feedback to pituitary and hypothalamus

Prolactin

Breast development and synthesis of milk

Negatively regulated by dopamine

Vasopressin (ADH)

Peptide hormone, synthesized in hypothalamus, stored in posterior pituitary

ADH triggers

sense of thirst

ADH increase

number of water channels in renal collecting tubules/ducts called aquaporins

aquaporins increase

water reabsorption

high osmolarity increases

ADH production

Volume always takes precedence

compared to osmolality

Paracrine and autocrine regulation are more

localized

Paracrine and autocrine are technically

not part of the endocrine system

Paracrine affect

cells next door

Autocrine affect

its own cell, or cell of same exact type nearby

cytokines, interleukins, interferons, tumor necrosis factor

endothelium produces nitric oxide and bradykinin which stimulate

relaxation of vascular smooth muscle

endothelin promotes

vasoconstriction

eicosanoids

function mostly by system, mostly looking at prostaglandins

prostaglandins give you

fever