Describes the different types of chemical messengers in mammalian body. This explains their synthesis and mode of action also. A short account of neurohormones and neuroendocrine function is also included.

1. Chemical messengers
DR. Radhakrishna G Pillai
Department of Life Sciences
University of Calicut

2. Categories of chemical messengers
• Local chemical messengers
• Neurotransmitters
• Neuropeptides
• Hormones
• Pheromones

3. Local messengers
• Chemical messengers secreted by certain cells
• Alter physiological conditions in the immediate
vicinity
• Act on same cells (Autocrine) or
• Adjacent cells (Paracrine)
• Do not accumulate in blood
• Eg Lumones: produced in gut-regulate digestion
– Histamine : secreted by mast cells in wounds- inflammatory
response

4. Autocrine & paracrine controls

5. Hormones
• Signaling molecules synthesized within the body that
– regulate and coordinate physiological and metabolic
functions
• Act on receptors located on or in target cells
• Produced by specialized secretory cells that are either
– localized in secretary glands or
– within organs that have other primary functions
• Depending on the cellular origin and the means by which
they reach their targets, the cellular messengers are given
different names

6. Hormones
• The original definition of hormones was
– restricted to chemical messengers
– produced within glands of internal secretion and
– released into circulation in small quantities to act
on distant receptors
• The term hormone is derived from the Greek
word hormein: to excite

7. Hormones
• Recent definition of hormones also include;
– chemical messengers produced by other than specialized
secretary cells and
– Signaling molecules that reach their target receptors by
routes other than circulation
– act on the receptors of the cell that produced them
– Such messenger action is called autocrine (Greek
:autos meaning self)

8. Paracrine controls
• Chemical messengers acting on the receptors of adjacent
cells are called paracrine secretions (Greek: word: para,
adjacent)
– Eg. somatostatin in the pancreatic islets acting on
adjacent insulin and glucagon cells

9. Chemical messengers and their sources

10. Non glandular sources of CMs

11. Chemical messenger: mode of actions

12. Chemical messenger: mode of actions
• Chemical messages are transmitted to specific receptors
through
– the extracellular fluids
– across the synaptic gap
– blood
• When the chemical messengers stimulate receptors on
the cell that synthesized them hormone action is
autocrine
• Messages delivered to adjacent cells: paracrine and
• Circulated through plasma: endocrine

13. Neurotransmission & neuroendocrine action
• Nerve cell deliver chemical messages:
– in a paracrine fashion across a synaptic gap
represent neurotransmission, and
– through the blood, neuroendocrine action

14. Neuro endocrine system
• Endocrine system shares its signaling and coordinating
function with the nervous system
• The two systems have evolved to control and
integrate vital body functions
• Chemical messengers produced by nerve cells and
released from the axonal endings usually act in
endocrine or paracrine fashion
• Neural signaling molecules released into the synaptic
gap to activate receptors on the adjacent cell
membranes are called neurotransmitters

15. Specificity of neurotransmitters
• The specificity of the message is assured both by
– The specificity of receptors on the postsynaptic
membrane &
– The discrete physical alignment between axon terminals
of a specific type of neuron and the receptors on the
postsynaptic membranse of a particular cell

16. Neurotransmitters Vs hormones
• Neurotransmission is characterized by speed of
message transmission (milliseconds) and restricted
points of delivery
• Hormones act over a longer period of time
(seconds to hours) and are distributed diffusely
through the extracellular fluid/blood medium to a
large number of targets

17. Examples of neurotransmission
> Neurotransmitter acetylcholine released from the
axonal endings of the motor nerves into the synaptic
gap;
Act on the nicotinic cholinergic receptors on skeletal
and cardiac muscle fibers
<Neurotransmitter acetylcholine from parasympathetic
nerves act on muscarinic receptos in ganglia and glands
Sympathetic nerves release norepinephrine that act on
catecholaminergic postsynaptic receptors

18. Neurohormones
• Neural signalling molecules released into circulation are called
neuroendocrine secretions or neurohormones
• These messengers behave as hormones by their method of signal
transmission
• They reach their targets through the circulation
• The specificity of receptors on target cells assure the delivery of
endocrine message to specific targets
– Examples: antidiuretic hormone and oxytocin synthesized by the nerve
cells residing in hypothalamus and
– released into circulation from their nerve endings in the posterior
pituitary gland

19. Neurotransmission or neurosecretion
• Some cells disseminate chemical messages by a combination of
endocrine and neural mode of communication
– Eg. the sympathetic nerves communicate largely by neurotransmission of
norepinephrine (NE)
– Some NE is released in to general circulation: act as a neuroendocrine
messenger
• Cells of adrenal medulla are developmentally and evolutionarily
ganglionic neurons of the sympathetic nerves: lost their axons
• They release epinephrine (E) and NE into systemic circulation
• Their function altered from neurotransmission to neurosecretion

20. Hormones
• Eicosanoids: prostaglandins, thromboxanes,
leukotrienes, and prostacyclins are group of
signaling molecules included as hormones
• They are short-lived chemical messengers
• They exert autocrine, paracrine, and occasionally
endocrine action on their receptors
• NO: only inorganic signaling chemical messenger :
control a number of important functions

21. Hormone structure and synthesis
• By chemical structure, hormones fall into three groups: amines,
peptides and proteins and lipid derivatives
• Amine hormones are metabolites of amino acids
– Example: epinephrine, norepinephrine and dopamine
• They are collectively called catecholamines
• Synthesized from the aromatic amino acids phenylalanine and
tyrosine in the brain and in the adrenal medulla
• Frequently hormones synthesis is under the control of other
hormones
• Eg. cortisol controls the last enzyme Phenylethanolamine N-
methyltransferase (PNMT ) in the synthesis of epinephrine

22. Hormone production
• Epinephrine is synthesized from the aromatic amino
acids tyrosine and phenylalanine
• Phenylalanine is an essential amino acid that has to be
obtained in the diet
• Sympathetic nerves and central nervous system
synthesize NE
• Adrenal medullary cells produce NE and E
• Conversion of NE to E in the medulla is facilitated by the
adrenal cortical hormone cortisol

23. Synthesis of catecholamines

24. Storage and release of hormones

25. Storage and release of hormones
• Hormones are released mainly in two ways
• Amine and peptide hormones are stored in
storage vesicles before release
• Their secretion is controlled by neurotransmitters,
hormones or metabolites
• Neural influence impose rhythmicity to hormone secretion
• Various secretagogues promote fusion of vesicles and cell
membrane
• The wall of the vesicles rupture
• The hormones are given out by exocytosis into blood or
extracellular fluid

26. Storage and release of hormones
• Steroid hormones leave the Golgi
apparatus in transport vessicles
• Released into circulation by exocytosis
without being stored within the cytoplasm
• This type of hormone secretion is called
constitutive
• Here the control of hormonal response is
at the stage of hormone synthesis rather
than hormone release

27. Regulated release of hormones
• Peptide and amine messengers are stored in secretary vesicles
• Their release requires transduction of hormonal, neural, and
metabolic stimuli by way of intracellular calcium or second
messengers
• The release of steroid hormones is constitutive
• Here hormonal, neural, and metabolic stimuli control steroid
hormone synthesis
• Immediately the hormone are released from transport vesicles

28. Quantity released
• Hormones are released in nm to picomolar concentrations
• They circulate in the blood at such low concentrations
• Success of hormone mediated response transmission rely
on the specificity and high affinity of their binding to the
receptors
• Most hormones are secreted in intermittent rather than
continuous fashion
• Pulsatile hormone secretion probably serves to supply
hormones in quantities required for their action

29. Frequency of hormone release
• The frequency of basal hormone pulses ranges from minutes to
hours
• There are also seasonal rhythms of hormone release
• Various stimuli can acutely increase or decrease hormone
secretion
• Eg. acute change in secretion of some hormones during exercise
• Compensatory changes in hormone secretion usually result from
metabolic, neural or hormonal feedback
• This feedback control is over the normal hormone secretion
signaling: the secretion rate is out of alignment with the acute
need for hormone action

30. Pattern of hormone release and its effect
• The temporal pattern of hormone secretion is of remarkable biological
significance
• The same quantity of hormone can have opposite biological functions
when it is delivered in intermittent as opposed to tonic fashion
• Eg. lack of growth stimulation by tonic administration of GH
• Normal menstrual function by a circhoral (1 pulse/hr) secretion of LH
• Lower or higher or tonic release of LH suppress menstrual cycle
• Modulation of biological response by changes in the temporal pattern
of hormone secretion is often exploited for specific purposes
• Tonic administration of gonadotropins has been successfully used to
achieve contraception

31. Transport of hormones
• Peptide, amine and protein hormones are water
soluble, and most of them circulate freely
• All of lipophilic steroid hormones, growth hormone
and some growth factors circulate bound to carrier
proteins
• Albumin and pre albumin non-selectively bind to and
transport a variety of small messenger molecules
• Globulins have single high-affinity binding sites for
specific steroid and amine hormones

32. Importance of hormone binding to carriers
• Binding hormones to carriers extends the period of their
availability and action by
– Preventing their rapid clearance from plasma
– By keeping some of the hormone from circulating in the free
form and diminish the magnitude but extend the duration of
hormone action
– Insulin-like growth factors are protected from degradation and
the duration of their biological action extended for hours by the
complex system of binding proteins
• In some instances (for example GH), binding proteins have
almost identical structure to cell receptors and may
facilitate the binding of the hormone to the receptor
• Thus the binding proteins may facilitate hormone action

33. Degradation of Hormone
• To be most effective, hormones need to reach their target
receptors in intermittent fashion. Why?
• Receptors become down regulated or less sensitive to
hormone action when;
– hormones are present in unphysiologically high concentrations or
– for abnormally long periods of times
• Hormone degradation avoids these situations
• Hence it is necessary prerequisite for optimal hormone
sensitivity and action

34. Degradation of hormones
• Hormones are changed into metabolicaly inactive form
either in target cells or in the liver and kidney
• A number of enzymes participate in metabolic
degradation of hormones
• The speed with which the hormones are metabolized
depends on;
– whether they travel free in plasma
– as well as on their molecular structure and
– the characteristics and location of their degrading enzymes
• The half-lives of hormones vary from seconds to hours

35. Half life of some chemical messengers

36. Thank you
pillai_radhakrishna@hotmail.com
0091 9495554891