CHEMICAL COMMUNICATION - HORMONES

I. CELLULAR COMMUNICATION A. Gap junctions effective communication between adjacent cells B. Neurons 1. Communication by electrical charge via direct line 2. Very rapid response time; specific response C. Hormones 1. Message sent by one system, through blood stream, to a target cell 2. Generally slower acting than neuro, but pervasive II. GENERAL PRINCIPLES OF ENDOCRINE PHYSIOLOGY A. Cell-to-cell signaling: Endocrine, Neurocrine, Paracrine, Autocrine B. Chemical Hormones: delivered by circulation to target organ. C. Hormone storage and release 1. Hormones synthesized and stored in secreting cell 2. External signals stimulate release III. HOW MESSAGES ARE DELIVERED/INTERPRETED A. Peptide and catecholamine hormones 1. Bind with surface membrane receptor; transduction to a signal generator 2. Second messengers produced, e.g., cAMP, Ca2+, cGMP, inositol triphosphate 3. Second messengers activate a cascade of reactions B. Steroid Hormones 1. Derived from cholesterol; include sex hormones 2. Enter target cells, bind with cytoplasmic receptor & enter nucleus 3. Act by altering pattern of gene expression IV. HORMONES RELEASED BY THE PITUITARY GLAND A. Pituitary composed of two distinct glands (lobes): anterior and posterior B. Posterior lobe of pituitary linked to hypothalamus by neurons 1. Antidiuretic hormone (ADH), also called vasopressin 2. Oxytocin C. Anterior lobe connected to hypothalamus by short blood vessels 1. Hypothalamic releasing hormones travel to anterior pituitary 2. Seven principal pituitary hormones are produced a. Thyroid-stimulating hormone (TSH) e. Growth hormone or somatotropin (GH) b. Adrenocorticotrophic hormone (ACTH) f. Melanocyte-stimulating hormone (MSH) c. Luteinizing hormone (LH) g. Prolactin (PRL): stimulates milk production d. Follicle-stimulating hormone (FSH) 3. Feedback controls IV. NON-PITUITARY HORMONES A. Thyroid Hormone - regulator of basal metabolism B. Antagonistic pairs of Hormones associated with metabolism 1. Control of plasma Ca2+ levels: balance of parathyroid and calcitonin 2. Regulation of blood glucose: insulin and glucagon C. Adrenal Gland 1. Adrenal Medulla - Noradrenaline and Adrenaline a. Neurotransmitters in sympathetic nervous system b. Hormones when released by adrenal medulla into the blood 2. Adrenal Cortex - Metabolic & Stress Regulator

COMMUNICATION and INTEGRATION within the ORGANISM

Chemical communication - the Endocrine System

example: cardiac muscle cells

examples: interleukins (cytokines); local factors like NO (nitric oxide)

examples: secretions from most endocrine glands

(a) gap junctions direct cellular communication

(b) autocrine & paracrine signals

(c) endocrine (hormone)

Means of cellular communication

(e) neurohormone (d) neurocrine (neurotransmitter)
examples: typical nerve-nerve or nerve-muscle connectioin examples: hypothalamic hormones

How do we get such a variety of responses??

First, we have a variety of hormones Second, for example, Different receptors Epinephrine ! receptor

Different Hormones

There are 3 kinds of hormones

1 AMINO ACID derivatives
e.g.,

different cell responses Epinephrine " receptor Epinephrine " receptor Glycogen deposits Vessel dilates

CATECHOLAMINE HORMONES
(& neurotransmitters)

Vessel constricts

Glycogen breaks down and glucose is released from cell Liver cell different cell responses

Nor-adrenaline

Adrenaline

PEPTIDE HORMONES -(amino acid polymers)

example: ADH

many; water soluble & cell impermeant membrane permeable

Intestinal blood vessel Third, for example,

Skeletal muscle blood vessel Different intracellular proteins

3 STEROID HORMONES -example: aldosterone

How do hormones work at the cellular level?

STEROID HORMONES from adrenal cortex & gonads

Chemical (Hormonal) communication between cells occurs through receptors

Surface

HO

CHOLESTEROL

A
Water soluble hormones
(1st messenger)

(which is also known as 2nd messenger)

operates through an intracellular messenger

Steroid hormones

HOW STEROID HORMONES WORK

Bind with a cytoplasmic receptor and relocate to the nucleus membrane permeable

How Peptide & AA-derivative Hormones Work

Operate through surface receptors & transduction via 2nd messengers

(1st messenger)

2nd Messenger Concept

An intracellular message is transduced from signals at the external surface
process takes time, thus fairly slow to come into play

Some important 2nd messengers

1. cAMP, cyclic AMP 2. IP3, inositol triphosphate 3. Ca++, calcium ions

ATP

AC
adenylate cyclase

cAMP

PDE
phosphodiesterase

AMP

Lets start with the cAMP 2nd messenger pathway

key metabolite

How do we alter cAMP level: stimulate production or inhibit destruction Receptor-coupled

AMP
stimulation of AC

ATP

AC
adenylate cyclase

cAMP

PDE
phosphodiesterase

ATP
O
Adenine

AC
adenylate cyclase

cAMP
cAMP

PDE
phosphodiesterase

AMP

Ribose -O-P-O-P-O-P-O-

AC

Adenine

Ribose

PDE

Adenine

Ribose -O-P-O-

Inhibition of PDE AC
adenylate cyclase

O O O--P O O O

ATP

O-P-O-P-OO O

cAMP
cAMP

PDE
phosphodiesterase

AMP

What does cAMP do?

Receptor activation complex

cAMP
Activated receptor

promotes the activation of protein kinases (phosphorylation of proteins)

Particularly protein kinase A (PKA)
(a protein kinase that is activated by c Amplification via a cascade

AMP)

Inactive AC ATP

Active AC cAMP Active PKA Phosphorylated activated protein

Inactive PKA

Protein Kinase A Cell Response

Inactive protein

How do hormones work in the organism?

Ca2+ and IP3 as intracellular messengers

Thyroid gland

cortex medulla

Cell Response

" cells - insulin ! cells - glucagon

Chemical Transmitters & Hormones studied thus far

G.I. System
Gastrin Secretin CCK secreted by stomach duodenum duodenum effect stim. H+ secretion HCO3- secretion enzyme & bile secretion

Antagonistic Hormones and Homeostasis: 2 Examples

Ex. #1. Insulin and Glucagon separately regulate blood glucose level
pancreas " cells - insulin ! cells - glucagon

C-V Respiratory Systems

Epinephrine Nor-epinephrine Acetylcholine adrenal medulla (neurotransmitter) (neurotransmitter) multiple effects multiple effects decreased heart rate by beta cells of pancreas

Immune System
Interleukins I and II (autocrine & paracrine mediators) Histamine & prostaglandin (chemoattractants)

Kidney
Antidiuretic hormone Aldosterone Atrial Natriuretic Factor collecting duct tubule tubule H2O permeability Na+ reabsorption Na+ loss

We need to keep blood glucose level constant

by alpha cells of pancreas

Hormonal control of calcium homeostasis in mammals

Ex. #2. Calcitonin and PTH separately regulate blood Ca2+ level
PTH = parathyroid hormone calcitonin

Hormones of the Hypothalamus & Pituitary Gland

Increase Ca2+ loss

parathyroid hormone

PTH

Hormones of the Hypothalamus & Pituitary Gland (contd)

Neurosecretory cells of the hypothalamus

Stress and the Adrenal Gland

#1 Hypothalamic releasing
hormones
GH-RH LH-RH FSH-RH TSH-RH ACTH-RH

Portal vessels

Posterior pituitary

Endocrine cells of the anterior pituitary

#2 Pituitary
HORMONE FSH and LH TSH ACTH Prolactin MSH GH

STEROIDS

hormones
adrenalin nor-adrenalin aldosterone cortisol

TARGET

Testes or ovaries
Gonadal steroids

Thyroid

Adrenal cortex

Mammary glands

Melanocytes

Liver, bones, other tissues

fight or flight

thyroxine

cortisol

ACTH = adrenocorticotropic hormone