CC3 – Introduction to Hormones
Endocrinology – study of hormones, the endocrine system and       Hormone – chemical messenger that travels through the
their physiology in the body.                                     bloodstream to target cells.
Major Endocrine Glands:                                               -    Secreted in very small amounts.
                                                                      -    Target cells have specific receptors for specific
     -     Hypothalamus
                                                                           hormones.
     -     Pituitary Gland (Hypophysis)
                                                                      -    Regulates response by affecting gene expression
     -     Thyroid Gland
                                                                           (gene transcription factors).
     -     Parathyroid Gland
     -     Pancreas (Islet of Langerhans)                         Target cells – cells with specific receptors to specific hormones
     -     Adrenal Glands                                         and reacts to them.
     -     Testes
                                                                  Effector cells – cells that exert the final intended effect of a
     -     Ovaries
                                                                  particular process.
Most Important Function of Hormones = Maintain optimum
                                                                  Hormone receptors – located on cell membrane or within
biochemical homeostasis (balance) of substances in the body.
                                                                  cytoplasm.
Other Functions = Growth, Development, Sexual Reproduction,
                                                                      -    Binding of hormone and receptor initiates a signal
Energy Production, Stress or Emergency Situations, Promote or
                                                                           which ultimately results to a biologic response.
Inhibit.
                                                                  Manners of Secretion:
Exocrine Glands vs. Endocrine Glands:
Exocrine = Glands with ducts and passes secretions to a luminal       1.   Autocrine – cell released hormone and hormone reacts
area (oral cavity or intestines or skin).                                  to the cell itself.
                                                                      2.   Paracrine – cell released hormone and hormone
Endocrine = Ductless glands that pass their secretions directly
                                                                           diffuses to nearby neighboring cells.
to the bloodstream or interstitial fluid.
                                                                      3.   Endocrine – cell released hormone and hormone
Nervous System vs. Endocrine System:                                       travels to the bloodstream and acts on distant target
                                                                           cells.
                                                                      4.   Juxtacrine – direct cell-cell contact.
                                                                      5.   Intracrine – cell released hormone intracellularly within
                                                                           itself and binds to a receptor located intracellularly.
                                                                      6.   Ectocrine (Pheromones) – organism releases a
                                                                           substance that causes an effect in another organism.
                                                                           (Dog releases something that cause effect on cats)
                                                                  Types of Hormones:
                                                                      -    Peptide Hormones
                                                                      -    Steroid Hormones
                                                                      -    Amine Hormones
                                                                  Peptide Hormones
                                                                      -    Consists of at least 3 amino acids.
                                                                      -    Water-soluble and is capable of freely circulating in
                                                                           the blood.
                                                                      -    Most abundant and is stored in vesicles.
                                                                      -    Only acts on receptors found on the cell surface.
    -      Requires the help of messenger enzymes inside the       G Protein is normally bound by Guanosine Diphosphate
           cell.                                                   (GDP) which acts like an “off signal” to the G Protein. Once
                                                                   the peptide hormone receptor binds to the G Protein, this GDP
                                                                   is converted to GTP (Guanosine Triphosphate) which acts
*Why can peptide hormones only act on the cell surface?            like an “on signal” to the G Protein and activates it.
Ans: This is because the cell membrane is composed of a            The activated G Protein, in turn, activates the enzyme
bilipid layer making it strongly hydrophobic.                      Adenylate Cyclase. By activating adenylate cyclase, the GTP
                                                                   bound to G Protein is hydrolysed back to GDP and G Protein
                                                                   become inactive again.
Peptide Hormone Synthesis: (Only for peptide hormones and
                                                                   Adenylate Cyclase acts to produce Cyclic Adenosine
very important)
                                                                   Monophosphate (cAMP) from ATP.
Since peptide hormones are proteins, it will always start off
                                                                   cAMP is free to diffuse throughout the inside of the cell and
with…
                                                                   triggers the activation of Protein Kinases which performs the
DNA (nucleus) – transcription process will take place to produce   intended cellular response of the original peptide hormone.
messenger RNA (mRNA).
                                                                   *Protein Kinases – enzymes that either phosphorylate or
mRNA (ribosomes) – translation process takes place to produce      dephosphorylate various proteins leading to the enhancing or
a PREPROHORMONE.                                                   inhibiting effect of the peptide hormone.
***Preprohormone consists of a signal peptide (pre) and a pro      1st Messenger = Original Peptide Hormone.
sequence (pro) which must be cleaved off to produce the fully
                                                                   2nd Messenger = Cyclic Adenosine Monophosphate.
active hormone.
Preprohormone (endoplasmic reticulum) – enzymes in the ER
cleave off the signal peptide to produce the inactive              Steroid Hormones
prohormone.
                                                                       -    Precursor substance of all steroid hormones is
Prohormone (Golgi apparatus) – enzymes in the Golgi                         CHOLESTEROL.
apparatus cleave off the pro sequence to produce the fully             -    Has a complex ring structure due to cholesterol.
active hormone and is packaged to a secretory vesicle for              -    Precursor Hormone of All Steroid Hormones =
release.                                                                    Pregnenolone.
                                                                       -    Lipophilic and Hydrophobic.
                                                                       -    Not stored within secretory vesicles.
Peptide Hormone Effect Mechanism: (very impt)                          -    Requires protein carrier molecules to be transported in
                                                                            the blood.
Peptide hormones travel to the bloodstream and binds with
                                                                       -    Slower acting compared to Peptide Hormones (since it
the cell surface receptor in its target cell.
                                                                            still requires protein carriers).
Since a peptide hormone CANNOT go inside the cell, it can only         -    Has longer half-life.
bind to the cell surface receptor. Once bound, it changes the          Types     of    Steroid      Hormones:   (Adrenal    Cortex
shape of the receptor and binds with a nearby inactive G               Hormones, Testes and Ovaries)
Protein.                                                               -    Glucocorticoids (cortisol)
                                                                       -    Mineralocorticoids (aldosterone)
*G Protein – an integral protein (meaning it spans the whole
                                                                       -    Androgens
cell membrane) which is always found paired to a peptide
                                                                       -    Estrogen
hormone receptor.
                                                                       -    Testosterone
                                                                       -    Progestogens (progesterone)
Steroid Hormone Synthesis:                                              -    Catecholamines (Epinephrine and Norepinephrine)
    -    Occurs in the MITOCHONDRIA and ENDOPLASMIC                 Thyroid Hormones – behave like steroid hormones.
         RETICULUM of steroidogenic tissues.
                                                                    Catecholamines – behave like peptide hormones.
    -    Examples of Steroidogenic Tissues = Luteal Cells of
         Ovaries, Leydig Cells of Testis and Cells of Adrenal           -    Produced by the adrenal medulla and may act as
         Cortex.                                                             both neurohormones and neurotransmitters.
Steroidogenic      Acute     Regulatory    Protein   (StAR)    –
transports    cholesterol     from   the   cytoplasm    to    the   Other Amino Acids used to Synthesize Amine Hormones:
mitochondria and is the rate-limiting step in the production of
                                                                        -    Tryptophan = Melatonin and Serotonin.
steroid hormones.
                                                                        -    Glutamic Acid = Histamine.
StAR picks up cholesterol from cytoplasm and then transports it
to the mitochondria where enzymatic steps are carried out
converting cholesterol to steroid hormones.                         Factors for Control of Endocrine Activity
                                                                        -    Rate of Production
                                                                        -    Rate of Delivery
Where does cholesterol used for steroid hormone synthesis
                                                                        -    Rate of Degradation and Elimination
come from?
                                                                    Control of Hormone Release:
    -    Acetate
    -    Cholesteryl Ester                                              1.   Substrate Control (Humoral)
    -    Low-Density Lipoproteins (LDL)                                 -    Glucose concentration regulating insulin release.
                                                                        -    Calcium concentration regulating parathyroid hormone
                                                                             release.
Steroid Hormone Effect Mechanism:                                       -    Sodium concentration regulation aldosterone release.
                                                                        2.   Nervous Control (Neural)
A steroid hormone is carried through the blood by a protein
                                                                        -    Posterior pituitary hormones and adrenal medulla are
carrier. Once it reaches its target cell, it is released from its
                                                                             both directly controlled by the nervous system.
protein carrier.
                                                                        3.   Trophic Hormones (Hormonal)
Since a steroid hormone is capable of directly entering the             -    TSH regulating T3 and T4 release.
cell (bilipid layer is hydrophobic and steroids are hydrophobic),       -    Corticotropin Releasing Hormone regulating ACTH
it attaches to its receptor within the cytoplasm.                            release.
                                                                        -    Usually produced by hypothalamus and anterior
The complex then directly enters the nucleus where it binds
                                                                             pituitary gland.
and activates a specific gene on the DNA of the cell. This
activated gene causes the production of an mRNA that codes
for protein production causing the desired effect of the            Feedback Control of Hormone Secretion:
steroid hormone.
                                                                    Negative Feedback – prevents excessive stimulus of a
                                                                    substance, hormone or activity by releasing a hormone which
                                                                    acts to decrease the stimuli.
Amine Hormones
                                                                    Example 1:
    -    Derivative of the amino acid TYROSINE.
                                                                    Stimulus = Hyperglycemia in DM patient.
    -    Capable of behaving as Peptide or Steroid Hormones.
                                                                    Body Response = Secrete Insulin which acts to lower the
Types of Amine Hormones:
                                                                    increased blood glucose in order to maintain homeostasis.
    -    Thyroid Hormones (T3 and T4)
Example 2:                                                             -    Example = Hypothalamus (TRH) and Pituitary Gland
Stimulus = Excessive Intake of Calcium Supplements                          (TSH).
Body Response = Secrete Calcitonin which acts to lower the         Disorders of the Endocrine System:
increased blood calcium.
                                                                   Primary – problem is within the gland itself.
***Conclusion: Negative Feedback = Lower something that has        Example: Primary Hypothyroidism would be caused by damage
been increased.                                                    or removal of the thyroid gland itself.
Positive Feedback – involves a lot of variables wherein 1          Secondary – problem is with the pituitary gland.
variable acts to increase the other variables.                     Example: Secondary Hypothyroidism occurs as a result of a
                                                                   pituitary adenoma (tumor that is exerting pressure on the
Example 1:
                                                                   pituitary gland) causing a decreased release of TSH resulting to
Stimulus = Uterus Contraction during Pregnancy                     lesser stimulation of thyroid gland.
Body Response = Secrete Oxytocin which acts to increase the        ***Almost all Secondary Disorders are due to Pituitary Adenoma
widening and contraction of the uterus to facilitate childbirth.   or Accidents involving Pituitary Gland damage.
Example 2:                                                         Tertiary – problem is with the hypothalamus.
Stimulus = Excessive Intake of Calcium Supplements                 Example: Hypothalamic damage = Lack of Thyrotropin
                                                                   Releasing Hormone = Lack of TSH = Lack of Thyroid
Body Response = Secrete Thyroid Stimulating Hormone (TSH)
                                                                   Stimulation = TERTIARY HYPOTHYROIDISM
which increases the activity of the Thyroid Gland to secrete
more Calcitonin.
***Conclusion: Positive Feedback = Hormone increases the
effect of another hormone.
Feedback Loops – a regulating system that is composed of
both positive and negative feedbacks.
***Both positive and negative feedback may occur in one whole
feedback loop.
Open-Loop Negative Feedback – refers to phenomenon of a
negative feedback with a modifiable set point.
    -    Most endocrine feedback loops are of this type.
Short Feedback Loop – feedback between effector cell and
pituitary gland.
    -    Example = Thyroid Gland (T3 and T4) and Pituitary
         Gland (TSH)
Long Feedback Loop – feedback at the level of the
hypothalamus.
    -    Example = Thyroid Gland (T3 and T4), Pituitary Gland
         (TSH) and Hypothalamus (TRH)
Ultrashort Feedback Loop – feedback between pituitary gland
and hypothalamus.