Introduction to Endocrinology (Chapter 75)

Lacaden, LMGc

SIGURADONG NAGBASA NA KAYO

NG BOOKSO REVIEW NA LANG TO
NG CHAP75 HA! Chemical Structure and Synthesis of
Chemical Messengers Hormones
1. Neurotransmitters Proteins and Polypeptides
o from axon terminals of neurons to o Proteins 100 or more AAs; Peptides
synaptic junctions >100 AAs
o act locally to control nerve cell o Synthesized in RER
functions. o Preprohormones⇒Prohormones⇒
2. Endocrine hormones (Transferred to Golgi, packed into
o from glands or specialized cells into secretory vesicles) ⇒ active
the circulating blood hormones and inactive fragments
o influence function of target cells at (by enzymes in the
another location vesicles)⇒vesicles are stored within
3. Neuroendocrine hormones the cytoplasm
o from neurons into the circulating o Give examples: ___
blood
o influence the function of target cells Steroid Hormones
at another location o Consist of three (3) cyclohexyl rings
4. Paracrines and a cyclopentyl ring
o from cells into the ECF o Very little hormone storage
o affect neighboring target cells of a (cholesterol esters, anong
different type. kinalaman?__)
5. Autocrines
o from cells into the ECF Amine Hormones
o affect the function of the same cells o derived from tyrosine
that produced them. o formed by enzymes in the cytoplasm
6. Cytokines o Thyroid Hormones = synthesized
o peptides and stored in the thyroid gland
o from cells into theECF ⇒incorporated into thyroglobulin
o function as autocrines,paracrines, or ⇒thyroglobulinsare split, releasing
endocrine hormones free hormones >thyroid hormones
o Examples: interleukins and other combine with plasma proteins
lymphokines (thyroxine-binding globulin) >
o Cytokine hormones (e.g., leptin) plasma proteins slowly release the
produced by __? hormones to the target tissues

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 o Catecholamines are released from
adrenal medullary cells by
exocytosis; exist in free form or in
conjugation with other substances in
the blood.
Clearance of Hormones From the Blood
o Two factors that increase /decrease
the concentration of hormone in the
blood; Rate of Hormone Secretion
and Rate of Removal
o Metabolic Clearance Rate = Rate of
disappearance of hormone from
plasma/Concentration of hormone
Ways Hormones are Cleared from the
Plasma
1. Metabolic destruction by the tissues
2. Binding with tissues
3. Excretion by the liver into the bile
4. Excretion by the kidneys into the
urine
Mechanism of Action of Hormones
Locations of hormone receptors
1. In or on the surface of the cell
membrane - mostly for _, _and_
hormones
2. In the cell cytoplasm -
primary receptors for_
hormones
3. In the cell nucleus -
receptors for the _
hormones
Down-regulation of the
receptors occur as a result of:
1. Inactivation of some of
the receptor molecules
2. Inactivation of some of the
intracellular protein signaling
molecules
3. Temporary sequestration of the
receptor to the inside of the cell
4. Destruction of receptors by
lysosomes after they are internalized
5. Decreased production of receptors
Up-regulation by some hormones
o stimulating hormone induces greater
than normal formation of receptor or
intracellular signaling molecules by
the target cell
o greater availability of the receptor
for interaction with the hormone
Intracellular Signaling After Hormone
Receptor Activation
Ion Channel-Linked Receptors
o causes a change in the structure of
the receptor, usually opening or
closing a channel for one or more
ions
G Protein-Linked Receptors
o indirectly regulate the activity of
target proteins
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 o coupling with heterotrimeric
guanosine triphosphate (GTP)-
binding proteins (G proteins)
o Displacement of GDP by GTP
causes the α subunit to dissociate
from the trimeric complex and to
associate with other intracellular
signaling proteins: these proteins, in
turn, alter the activity of ion channels
or intracellular enzymes such as
adenylyl cyclase or phospholipase
C, which alter cell function.
o Some hormones are coupled to
inhibitory G proteins (denoted as Gi
proteins), whereas others are coupled
to stimulatory G proteins (denoted as
Gs proteins)
Enzyme-Linked Receptor Protein
o receptors that function directly as
enzymes or are closely associated
with enzymes that they activate.
o E.g. Leptin Receptor (member of a
large family of cytokine receptors)
o Adenylyl Cyclase (catalyzes the
formation of cAMP)
Second Messenger Mechanisms for
Mediating Intracellular Hormonal
Functions
o Adenylyl Cyclase - CAMP Second
Messenger System
o Cell Membrane Phospholipid Second
Messenger System
o Calcium - Calmodulin Second
Messenger System
Sequence of Events in Steroid Function
1. The steroid hormone diffuses across
the cell membraneand enters the
cytoplasm of the cell, where itbinds
with a specific receptor protein.
2. The combined receptor protein–
hormone then diffusesinto or is
transported into the nucleus.
3. The combination binds at specific
points on theDNA strands in the
chromosomes, which activatesthe
transcription process of specific
genes to formmRNA.
4. The mRNA diffuses into the
cytoplasm, where itpromotes the
translation process at the
ribosomesto form new proteins.
Two Features of Thyroid Hormone
Function in The Nucleus
1. They activate the genetic
mechanisms for the formation of
many types of intracellular proteins
— probably 100 or more. Many of
these intracellular proteins are
enzymes that promote
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 enhancedintracellular metabolic
activity in virtually all cells of the
body.Once bound to the intranuclear
receptors, the thyroid hormones can
continue to express their control
functions for days or even weeks
Measurement of Hormone
Concentrations in the Blood
o Radioimmunoassay
o Enzyme-Linked Immunosorbent
Assay (ELIZA)