Chapter 4 Cell Signaling and Endocrine Regulation
I.
Overview
1.
Cells communicate either
directly via gap junctions or indirectly via autocrine, paracrine, endocrine,
and some neural signaling, when the signaling cell releases a chemical messenger
into the extracellular environment.
2.
Gap junction is an aqueous
pore between two adjacent cells that allows ions and small molecules to move
freely from cell to cell.
3.
Autocrine is a type of cell
signaling pathway in which a single cell signals another cell of the same type,
including itself.
4.
Paracrine is a type of cell
signaling pathway that is involved in local signaling between nearby cells
through the interstitial fluid by diffusion.
5.
Endocrine is a type of cell
signaling pathway in which the signaling molecule (hormone) is released into the
bloodstream and affects a distant cell of a different type.
6. Exocrine is a type of cell signaling pathway that the signaling molecule is released from organism into the external environment, such as pheromones.
II.
The Biochemical Basis of Cell
Signaling
1.
General features of cell
signaling
(1)
Gap junctions are composed of
cylindrical proteins (connexins in vertebrates or innexins in invertebrates)
assembled in groups of 4 or 6 to form doughnut-like pores in the cell membrane.
(2)
The hormones of the endocrine
system are released by specialized endocrine glands. These endocrine glands lack
ducts (are ductless) and release hormones directly into the extracellular fluid and into the
circulatory system for transport around the body.
(3)
Pheromones are produced in
exocrine glands that secrete chemicals into ducts that lead to the surface of
the body, such as saliva.
2.
The
chemical composition of the messenger
determines the type of signaling mechanism in endocrine system.
(1)
There are 6 main classes of
chemicals that are known to participate in cellular signaling in animals:
peptides, steroids, amines, fatty acid derivatives, purines, and gases.
(2)
Hydrophilic messengers
function by binding to membrane receptors and trigger signal transduction
pathway.
(3)
Hydrophobic messengers diffuse
freely across cell membranes, bind to nuclear receptors, and trigger gene
expression pathway.
3.
Peptides
(1)
Amino acids, peptides, and
proteins can all act as signaling molecules.
(2)
Peptide and protein messengers
contain 2-200 amino acids in length. Chains of fewer than 50 amino acids are
usually called peptides, while the word proteins is used for longer chains.
(3)
Peptide messengers are
released by exocytosis and bind to transmembrane receptors.
4.
Steroids
(1)
There are 3 major classes of
steroid hormones in vertebrates: mineralocorticoids (e.g., aldosterone),
glucocorticoids (e.g., cortisol, cortisone, and corticosterone), and
reproductive hormones (e.g., estrogen, progesterone, and testosterone).
(2)
Steroid messengers bind to
carrier proteins during transport in blood, bind to intracellular steroid
receptor (nuclear receptor), and regulate the gene expression of target cells.
5.
Amines
(1)
Many amines are synthesized
from amino acids, e.g., catecholamines (dopamine, norepinephrine, and
epinephrine secreted from chromaffin cells of the adrenal medulla) and thyroid
hormones are synthesized from tyrosine.
(2)
Thyroid hormones (e.g., 3, 5,
3'-triiodothyronine (T3) and 3, 5, 3', 5'-tetraiodothyronine (T4;
thyroxine)) are hydrophobic messengers.
6.
Communication of the signal to
the target cell
(1)
Ligand-receptor interactions
are specific.
1)
Agonist is a substance that
binds to a receptor, and initiates a signaling event like a natural ligand.
2)
Antagonist is a substance that
binds to a receptor, but does not stimulate a signaling event, preventing the
binding of the natural ligand.
(2)
Ligand-receptor binding
affinity can vary.
1)
The strength of binding
between a ligand and a receptor can be expressed by the dissociation constant (Kd).
The dissociation constant is defined as the concentration of messenger at which
half of the receptors on the cell surface are bound to ligand.
2)
Alternatively, the strength of
ligand-receptor interactions can be expressed by the association constant (Ka),
which is defined as the inverse of the dissociation constant.
III.
Introduction to Endocrine
Systems
1.
Characteristics of endocrine
systems
(1)
The word hormone is derived
from the Greek root hormao, meaning “to excite or arouse”.
(2)
To be classified as a hormone,
a substance must:
1) Be secreted by endocrine glands
2) Be transported via the circulatory system
3) Bind to a specific receptor
4) Exert its effects at extremely low concentrations
5) Exert its effects at long distance
6) Have a signaling function
(3)
Hormone levels are regulated
by negative or positive feedback loops.
(4)
The actions of insulin show
the principle of negative feedback. Insulin is secreted from the islets of
Langerhans of pancreas when blood glucose rises.
(5)
The actions of oxytocin (OXT)
show the principle of positive feedback. Oxytocin is released from the posterior
pituitary at the onset of parturition to increase uterine contractions.
(6)
The pituitary gland:
1)
The pituitary gland
(also called the master gland) is divided
into 2 distinct sections: the anterior pituitary (adenohypophysis) and the
posterior pituitary (neurohypophysis).
2)
The anterior pituitary is
derived from a portion of the ectoderm of the roof of the Rathke's pouch.
3)
The anterior pituitary secrete
6 hormones:
i)
Prolactin (PRL) plays roles in
the development of mammary glands in mammals; sexual behavior and growth, and
the regulation of larval development and ion/water balance in nonmammalian
vertebrates.
ii)
Thyroid-stimulating hormone
(TSH) play a role in the thyroid gland
for T3 and T4 secretion.
iii)
Adrenocorticotropic hormone
(ACTH) regulates the release of mineralocorticoids and glucocorticoids from the adrenal cortex.
iv)
Follicle-stimulating hormone
(FSH) play a role in gonads for sexual hormone secretion.
v)
Luteinizing
hormone
(LH)
also play a role in gonads for sexual hormone secretion.
vi)
Growth hormone (GH) play a
role in liver and others for growth.
4)
TSH, ACTH, FSH, and LH
participate in third-order pathways are called tropic hormones.
5)
The anterior pituitary also
includes a region called the intermediate lobe. In adult mammals, the
intermediate lobe is simply a thin sheet of cells, but it can be quite large in
other vertebrates. The intermediate lobe secrets melanocyte-stimulating hormone
(MSH) which is regulated by MSH-releasing hormone (MRH) and MSH-inhibiting hormone (MIH) secreted from the
hypothalamus.
6)
The posterior pituitary is
derived from neural ectoderm, and is an extension of a part of the hypothalamus.
Neurons that originate in the hypothalamus travel through the infundibulum to
terminate in the posterior pituitary. Neurons in hypothalamus synthesize 2 hormones oxytocin and
antidiuretic hormone (ADH), package them into secretory vesicles, and transport
along the neuron via axonal transport to the posterior pituitary.
(7)
The hypothalamus secrete 7
hormones in the hypothalamus-pituitary portal system:
i)
Prolactin-releasing hormone
(PRH) and ii) prolactin-inhibiting hormone (PIH) regulate the secretion of
prolactin.
iii)
Thyrotropin-releasing hormone
(TRH) regulates TSH secretion.
iv)
Corticotropin-releasing
hormone (CRH) regulates the secretion of ACTH.
v)
Gonadotropin-releasing hormone (GnRH)
regulates FSH and LH secretion.
vi)
GH-releasing hormone (GRH) and
vii) GH-inhibiting hormone (GIH) regulate the
secretion of growth hormone.
(8)
Antagonistic hormone pairs
provide precise regulation.
1)
In an antagonistic pair, one
hormone activates a process, whereas the other hormone inactivates it.
2)
The regulation of blood
glucose is controlled by insulin and glucagon secreted from β and α cells in the
islets of Langerhans of pancreas, respectively.
3)
The regulation of blood Ca2+
levels is controlled by parathyroid hormone secreted from the parathyroid glnds
to stimulate Ca2+ release from bone and increase Ca2+
reabsorption by the kidneys, and calcitonin to inhibit Ca2+ release
from bone and reduce Ca2+ reabsorption by the kidneys.
4)
The regulation of blood
osmolarity is controlled by ADH to increase water reabsorption by the kidneys,
and atrial natriuretic peptide (ANP) secreted from the atrium of heart to
inhibit water reabsorption by the kidneys.
(9)
Hormones can demonstrate
additivity and synergism.
1)
Additive effect: hormones can
interact positively to increase the activity of a physiological system. The
additivity is the effect of the hormones in combination and is equivalent to the
sum of the effects of each hormone in isolation, e.g., glucagon + epinephrine.
2)
Synergistic effect: sometimes
a combination of hormones can have an effect much greater than the sum of the
effects of the hormone alone e.g., glucagon + epinephrine + cortisol. Synergism
is a situation in which two agents have a combined effect greater than the sum
of the effects of the two agents applied individually.
2.
Evolution of endocrine systems
(1)
Hyperglycemic hormones are an
example of an invertebrate neurohormone.
1)
In invertebrates, the
regulation of glucose is regulated by a neuropeptide called crustacean
hyperglycemic hormone (CHH) in crustaceans (crabs and shrimps), rather than
insulin and glucagon that are used for glucose regulation in vertebrates.
2)
CHH is synthesized in
secretory neurons that are clustered into X-organ within the crustacean
eyestalk.
3)
The sinus gland is a storage
and release site for CHH.
4)
CHH binds to a transmembrane
receptor that activates guanylate cyclase and increases the concentration of
cGMP within the target cell, acting as a second messenger to trigger the signal
transduction pathway.
(2)
Ecdysone is structurally
similar to vertebrate steroid hormones. Ecdysone is one of the ecdysteroid
hormones of arthropods that is responsible for controlling many aspects of
development, including ecdysis.