Slide 1

Introduction to Endocrinology

Dr. Bruce Wright

 255-6398
 brucewright@RossU.edu
Room 15, above Classroom 6

Office Hours: Open Door

- “Practice Questions are posted in the Practice

Questions Tab on ecollege (after week 14)

A physiology session despite the name.

Slide 2

• Introduction to Endocrinology
• Learning Objectives:

• 1. Name, draw, and describe the major organs of the endocrine system,
and identify each as a primary, secondary, or transient endocrine organ.
• 2. Describe the following classes of signaling molecules: Amines,
peptides, steroids, prostanoids, and gases.
• 3. Summarize the general concepts underlying hormone control and
secretion, including homeostasis, hormone-specific secretion patterns,
and cellular mechanisms of secretion.
• 4. Name, compare, and contrast the most common receptor and signal
transduction systems at hormones’ target cells.
• 5. Define up-regulation and down-regulation of receptors and give
examples of each in normal and pathophysiological states.
• 6. Describe hormone transport, half-lives, and clearance in an
endocrine context. 2

Unless otherwise indicated (e.g. SUPPLEMENTAL material), all materials in the

main slide and the notes are testable for this and every following Endocrine
Physiology lecture. That said, one’s primary focus should be on what is on the
main slides.

The following materials are recommended reading from Semester 1 in preparation for
Endocrine Systems in Semester 2, either 02 or 2X.

• Ecollege, PDF, Semester 1 Week 3, Introduction to Cellular Signaling.

• Ecollege, PDF, Semester 1 Week 8, Cellular Signaling.
• Ecollege, PDF, Semester 1 Week 9, Basic Concepts in Immunity 2016
• Ecollege, PDF, Semester 1 Week 10, Cytokines
• Ecollege, PDF, Semester 1 Week 11, Neuromuscular Transmission, Slide 3.
Slide 3

The major endocrine glands

Primary endocrine gland

Secondary endocrine gland

Heart
Transient endocrine gland (Rt Atrium)
or endocrine structure
Liver

Placenta
Corpus
Luteum

Objective 1.
Note: There is a PDF table posted in Canvas immediately below this presentation. You
are responsible for the material in that table.
The major endocrine glands were once generally considered to be those organs whose
primary purpose is the production and release of chemical messengers that travel
through the body. However, because several organs with major endocrine products
(e.g., the kidney) have primary functions associated with other organ systems (e.g.,
urinary system), we classify those as secondary endocrine glands. Examples of these
would include the heart (Atrial Natriuretic Peptide, ANP) and adipose tissue (leptin).
The placenta is only found in females and then only for a short duration (part of
pregnancy), so this would be an example of a transient endocrine organ. Similarly, the
corpus luteum is a transitory endocrine structure within the primary endocrine gland
called the ovary.
Note: You will often find that both the hypothalamus and the pineal gland are often
referred to as primary endocrine glands, because at least for the hypothalamus, it is so
important. However, as the hypothalamus is first a part of the brain, and the brain would
be considered the secondary endocrine organ, the part of the brain known as the
hypothalamus must be secondary too, based on this definition. Similarly, the pineal
gland, long studied as a primary endocrine gland, is technically a secondary gland. In
contrast, the endocrine pancreas is absolutely a primary gland even though most of the
mass makes up an exocrine gland. This is because it has very defined structures within
the pancreas that only perform an endocrine function, unlike, say, neurons of the
hypothalamus.
You are required to know all the glands shown on this slide and the table (PDF)
posted separately from this presentation by their category and, when specifically
mentioned in endocrine physiology, their endocrine products (hormones,
paracrine agents, etc.) NOTE: I really DO test this, so don’t glide over this slide!
Slide 4

Three major classes of “hormones”

Based on structure
• Amines– derived from one or
two modified amino acids,
usually tyrosine (or tryptophan).
Can be hydrophilic or
hydrophobic.
• Peptides- derived from three or
more linked amino acids. Usually
hydrophilic.
• Steroids- derived from
cholesterol, includes Vitamin D3.
Hydrophobic.

• Plus Two “Hormone-Like” Classes

• Prostanoids– derived from fatty acid

(arachidonic acid), most are cytokines
• Gases – e.g., nitric oxide (NO),
hydrogen sulfide (H2S)
There are others, but these are the five you should know. 4

Objective 2.

One would think that it would be a relatively simple task to define the term “hormone”,
but this is not the case.

There are many names in many disciplines for molecules that act as messengers,
signal substances within or between cells. Neurotransmitters. Cytokines. Paracrine
agents. Chemotaxins. Second messengers. The list goes on.

The most restrictive definition of “hormones” in use today only includes those
substances that are secreted from some organ or tissue which may or may not be a
classical endocrine gland, but which once secreted always enter the blood and are
transported through the blood to some target site at which some specific response takes
place (Williams Textbook of Endocrinology 13th Ed., 2016, p.2).

That in many circumstances the exact same molecule may be secreted and affect an
adjacent cell to do the same thing that the hormone delivered by the blood route would
do, complicates the matter. Similarly, some classes of hormones (e.g., amines,
peptides, and steroids) were discovered sooner than others and are therefore
considered “classic” even though the other types of signaling molecules might be able
to follow the same route to their target cells. Thus, in discussion of endocrinology it is
often best to take the wide view; that regardless of naming conventions, those
molecules secreted from some organ or tissue and travel by some route to a target cell
to affect its function are at least “hormone-like”.
If you personally prefer to focus on more specific distinctions, perhaps because
someone in another discipline (e.g. immunology) uses a different term for the same
thing, for most purposes that’s fine. What’s most important is that you keep hold of the
main idea, which is of the signal substance that communicates between differing parts
of the body as a means to a greater end, changes in body function. As such, I teach
this topic and test this topic using the broad definition, in which prostanoids, gases, and
even purines or certain other “nonclassical” substances are hormones based on what
they do, not on how they get there, because it is the best way to avoid arbitrary term-
based limitations on discussion of the physiological actions and control of biological
processes using chemical signaling mechanisms.

Testing note: For every hormone you need to know in Endocrine Systems, you need to
know its class, because one of our clinicians and I could describe a clinical condition
describing a hormone’s action and instead of asking the hormone’s name, I’ll ask either
its class (second order question) or some general features about that class that are
applicable to the clinical condition (third order question). Alternatively, I could mention a
class and then turn it around for clinical conditions related to a hormone in that class
(second order). The non-genetic clinical conditions you are required to know are posted
in this presentation.
Slide 5

Patterns of hormone secretion

• Episodic Release: A specific stimulus arrives and the
hormone is released. If only paracrine/autocrine substances
are released, this can be called a “localized burst”.
– Insulin is an example of a hormone released when glucose levels
rise in the bloodstream.

• Pulsatile Release: A hormone is released in a series of

regularly timed short bursts, typically with time between the
bursts devoted to hormone action and metabolism
– Growth hormone is an example of a hormone released in short
bursts when stimulated to do so by hypothalamic hormones

• Circadian and other larger-timed rhythms:

Significantly more hormone is released at certain times of the
day (circadian), month, or year than at other points in the
respective time cycle.
55

Objective 3.

Please recall that for almost all peptide hormones and catecholamines, the hormone
molecules are stored in the same manner as neurotransmitters, within vesicles that can
be stimulated to fuse with the external membrane producing exocytosis of the contents,
while production of new hormones begin. This produces a faster release of the
hormone than would otherwise be possible. (See: Semester 1 readings). In contrast,
for almost all other types of hormones (and even for a few peptides), hormones are not
stored in the cell; instead they are produced when an outside signal prompts them to do
so, and then released immediately. They are not stored.

Quote, Guyton and Hall p. 929, “Superimposed on the negative and positive feedback
control of hormone secretion are periodic variations in hormone release that are
influenced by seasonal changes, various stages of development and aging, the diurnal
(daily) cycle, and sleep… In many cases, these cyclical variations in hormone secretion
are due to changes in activity of neural pathways involved in controlling hormone
release.” It is therefore best to think of a circadian or longer-timed rhythm as a
modulation of either episodic or pulsatile secretion patterns under complex controls (e.g.
with brain processing of optic light-dark input signals).
Slide 6

• Characterized by relatively stable time

periods between releases
Pulsatile Release
– producing “peaks” of high concentrations of
hormone.

• Baselines are typical of time periods of

very little secretion
– allows target receptors and cells time to
“reset”, to better respond to the presence of
the next “peak”.

• Both timing between peaks and quantity of

hormone secreted can be modulated.
– e.g., 1 GnRH peak/hr promotes LH secretion
but 1 GnRH peak/3 hrs promotes more FSH
secretion instead;
– See Reproductive Physiology for more details

12

Objective 3.
Slide 7

Episodic Release aka, EXPERIMENTAL CONDITIONS

• Baseline stays low until some condition

occurs that stimulates hormone release
(1) Acute release of
hormone-rich vesicles
• Acute release of hormone often starts
with exocytosis of stored materials (e.g.
preformed insulin)

• Further release (second stage) of newly

synthesized hormone occurs indefinitely

• Release ends only when the condition (2) Delayed continuous release
for stimulus ends of newly synthesized hormone

Note: There is no “time-based schedule” of release 13

Objective 3.

Though the specific example shown is for a water-soluble hormone (insulin), there are
also episodic release mechanisms for lipid-soluble hormones as well.
Slide 8

Three Types of Hormone Control

• Three overall patterns:

• 1. Homeostatic feedback, almost

always negative.
– Physiological Response-Driven vs.
– Endocrine Axis-Driven

• 2. Neural control:
– Includes adrenergic, cholinergic,
serotoninergic
– Can serve homeostatic feedback

• 3. Chronotropic control (modulation):

– Includes pulsatile, diurnal, menstrual,
seasonal, and developmental rhythms
– Involves neuronal signals
– Can modulate homeostatic feedback
8

Objective 3.

“The predominant mode of a closed feedback loop among endocrine glands is negative
feedback. In a negative feedback loop, “hormone A” acts on one or more target organs
to induce a change 9either a decrease or increase) in circulating levels of “component
B”, and the change in component B then inhibits secretion of hormone A. Negative
feedback loops confer stability by keeping a physiological parameter (e.g., blood
glucose) within a normal range…

There are two basic configurations of negative-feedback loops within the endocrine
system: A physiological response-driven feedback loop (referred to simply as
‘response-driven feedback’) and an endocrine axis-driven feedback loop (Fig. 32-2).
The response-driven feedback loop is observed in endocrine glands that control the
following conditions: Blood glucose levels (pancreatic islets), blood Ca++ and Pi levels
(parathyroid glands, kidneys), blood osmolarity and volume (hypothalamus/posterior
pituitary), and blood Na+, K+, and H+ (zona glomerulosa of the adrenal cortex and atrial
cells).
Slide 9

Homeostatic
Feedback
• In this example the regulated
variable is plasma glucose

• If it rises too high (hyperglycemia),

insulin is secreted to reduce it

• If it drops too low (hypoglycemia),

glucagon and/or catecholamines
(epinephrine) are secreted to
increase it

• Each activates a series of generally

opposing biochemical processes to
produce its change in blood glucose. 9

Objective 3.

The most typical feedback for homeostatic control of some variable, is negative
feedback. In the example above, the regulated variable is plasma glucose, which needs
to stay in a normal range. When glucose rises above the normal range as in our
previous example, the insulin acts in this simple example to convert excess glucose into
glycogen and increase glucose utilization. The combination of effects reduces blood
glucose until it is at the normal range.

In the same way, when glucose drops below the normal range, a different hormone
(glucagon) is secreted. It has as one of its effects the ability to cause glycogen to be
converted to glucose, or to produce glucose from other sources. These raise blood
glucose to normal. In this way by using primarily only two hormones with a few other
hormones for finer control, the glucose level in the plasma is theoretically always kept
“just right”, neither too high nor too low. This is a classic example of Physiological-
response driven negative feedback.

Another form of feedback not shown here is positive feedback, which is both quite rare
and usually quite specific to drive a one-way process such as labor and parturition. You
will need to know one form of positive feedback in Endocrine Systems 1 (see
Hypothalamus-Pituitary Histology & Physiology), but otherwise this is usually left to the
reproductive module, in which these feedback loops are most common.
Slide 10

Neural Control

• Nervous system
directly commands
hormone release.

• Often involves
neurons or related
neural tissue cells
as secretagogues.

10

Objective 3.

This is the classic example of neurocrine signaling. The cells in the adrenal medulla that
secrete catecholamines are derived from neural crest cells.

As seen on the previous slide, neural “control” can often be thought of as a subset of
the more general negative feedback control of physiological processes.
Slide 11

Chronotropic Control Example:

Circadian Cycle of Cortisol
Secretion
• Cortisol is the
primary human
glucocorticoid

• Cortisol
secretion peaks
at 9-10 a.m.

• Minimal
secretion at
midnight
11

Objective 3.

Remember, chronotropic control is actually more of a modulation of another control.

This is usually a pulsatile release; such that chronotropic modulation influences the
quantity of hormone released at each time.

With some fluctuations, the secretion of cortisol appears to peak after the beginning of
the “lights-on” part of this animal’s circadian cycle. It and its controlling hormone ACTH
is at its lowest early in the “lights-out” phase of the day, for most humans near midnight.

The circadian cycle of growth hormone (which unlike cortisol is anabolic), is the
opposite, it is at its circadian peak when cortisol is at its nadir. Since growth hormone
supports anabolism of many tissues and cortisol catabolism, it is good that they don’t
peak at the same time.
Slide 12

Target Cells and Tissue

• Target Cell: Any cell that can change its activity in some way, due to its
reaction to the presence of a given hormone.

• Target Tissue: A group of cells that collectively respond to the presence

of a given hormone at each individual cell.

• For most hormones, mass release of hormone molecules allow target tissues
to be affected, often within a single organ.

12

Objective 4.

Quote: “Although hormones can exert coordinated, pleiotropic control on multiple

aspects of cell function, any given hormone does not regulate every function in every
cell types. Rather, a single hormone controls a subset of cellular functions in only the
cell types that express receptors for that hormone. Thus, selective receptor expression
determines which cells will respond to a given hormone. Moreover, the differentiated
state of a cell will determine how it will respond to a hormone. Thus, the specificity of
hormonal responses resides in the structure of the hormone itself, the receptor for the
hormone, and the cell type in which the receptor is expressed.”
Slide 13

Hormone Receptors

• Component of Target Cell

• May be cell surface or

intracellular

• When hormone binds,

hormone-receptor
complex initiates some
activity change.

13

Objective 4.
Slide 14

Objective 4.

“Receptors can be divided into two basic classes based on their structure and
mechanism of action: membrane receptors and nuclear receptors (Table 3-1 and Figs.
3-4 and 3-5).”

Given the emphasis that this material was given in first semester cell control lectures,
you should be very familiar with both the receptor classes, the hormones/extracellular
ligands mentioned, and their mechanisms of action. While I am unlikely to ask
specifically about, say, retinoic acid, as a main topic in Endocrine Systems, it is a topic
you have covered before and thus is fair game for some degree of incorporation into a
cumulative-coded mini or final exam question. That said, it is wiser to know a lot about
the classical hormones than a little about all of them however obscure, I test what I
teach.

Similarly, much of the material that follows is cumulative with semester 1 cell signaling
lectures, which by definition begin with a chemical messenger and take you into cellular
responses. Endocrine Systems is in many ways the functional application of that
material now incorporated with synthesis, whole-body applications, and clinical
considerations, so I would recommend that if you have forgotten some of it, you take
advantage of being able to refer to it ad libitum.
Slide 15

Cell surface hormone receptors

require second messengers
H

Plasma Membrane

Acute Effects
Transcription
Growth &
Second Signaling pathway Metabolism
messenger

• Membrane-bound receptors are highly variable and hormone specific.

• Biomolecules binding to membrane-bound receptors indirectly
regulate transcription through second messenger signaling pathways.
15

Objective 4.

As stated previously, much of this material is potentially integrated with topics from other
disciplines in the biomedical sciences and cumulative with those of other modules in
semester 2, and fundamentals in semester 1. This of this as an opportunity to integrate
learning concepts for clinical application.

The advantage of using generally water-soluble hormones with cell surface hormone
receptors is that they are typically easily delivered to target tissues and they tend to
have very fast-on and fast-off responses within the cell, analogous to turning on or
turning off a light switch. Typically, these acute effects involve turning on and off
enzymes to mediate some quickly-regulated metabolic pathway. However, this signal
transduction system can also affect transcription of proteins which mediate cell
responses so even for water-soluble hormones (e.g. growth hormone) some processes
it affects won’t be fast at all (e.g. bone growth).

The disadvantage of using generally water-soluble hormones with cell surface hormone
receptors is that if the intracellular machinery isn’t already in place when the hormone
reaches the target cell, it’s like having a cut wire between the light switch and the light,
the switch may be flipped but the light won’t go on. Some hormones (e.g., cortisol)
affect the number of the proteins necessary to bind to and transduce a signal from the
surface receptor in the target tissue, thus modulating the effect of a second hormone
(e.g. epinephrine) that binds to this surface receptor. Such permissive effects are
discussed more in adrenal and thyroid physiology.
Slide 16

Steroids, thyroid hormones and some “vitamins”

bind with intracellular receptors.

H
Plasma Membrane

H
nR
Nucleus

Gene transcription

• Steroids, thyroid hormone, retinoic acid (active Vit A), and

calcitriol (the active form of Vitamin D) either diffuse across
Key
or are transported across the cell membrane.
Points • Some receptors start in cytoplasm, others in nucleus.
• Directly regulate gene transcription. 16

Objective 4.

The advantage of lipid-soluble hormones is that if you can get them to the cell, the cell
machinery for gene transcription and translation will always be there, so these
hormones can exert their effects. The cell receptors are intracellular, either in the
cytoplasm or in the nucleus. Gene transcription changes in the cell is the direct effect of
these hormones, and then those gene products affect or produce the final cellular
response. This may include producing cytoplasmic enzymes and/or cell surface
receptors that will help another hormone work better (a permissive effect).

The disadvantage of this route is a slow “speed”. If a hormone relies on gene

transcription and translation but not a second messenger system to exert its effect, the
effect won’t be observed until enough protein is made and processed in the Golgi, etc.
to be able to bring about the final action in the cell. Depending on the desired effect,
this could take hours to days. On the other hand, the effect of this one hormone
molecule may last for many days, until the proteins whose production the hormone
caused to be made are finally inactivated and/or recycled. So, these hormone effects
are both slower to start and slower to stop than are those of water-soluble hormones.
Supplemental: The few exceptions to this rule, in which lipid-soluble hormones bind to
surface receptors, are outside the scope of undergraduate endocrine physiology.
Instead they are part of residency-level neuroscience, under the class called
neurosteroids.
See https://www.sciencedirect.com/science/article/pii/S0149763412001728
Slide 17

General Feature Group 1 Group 2

features of Type of biomolecule • Steroids • Polypeptides
signaling • Iodothyronines (Thyroid • Proteins
biomolecules hormone) • Glycoproteins
• Calcitriol (“Vitamin D”) • Catecholamines (e.g.,
• Eicosanoids epinephrine)

Solubility properties Lipophilic Hydrophilic

Transport proteins Yes Usually No*

Plasma half-life Long (hours to days) Short (minutes)

Receptor localization Intracellular (almost always) Plasma membrane

Receptor signaling Receptor-hormone complexes Second messengers (cAMP,

pathways/mechanisms of bind to response elements and cGMP, Ca2+, DAG,
action act in the nucleus. phosphokinases, etc.)

17

Objectives 4 and 5.

The two major classifications of hormones based loosely on water solubility. You should know
this table and its contents and be able to apply it.
Slide 18

Hormone action is dependent on the concentration and the

receptor density at the site of action, not in the plasma.

Systemic (plasma) concentrations of ‘locally-acting’ biomolecules

likely do not represent the true level acting at the target site.

Because the biomolecule binds rapidly with receptors upregulated at

Why? the site of release, thereby keeping ‘escape’ into the systemic
concentration at a minimum.

Systemic concentrations of endocrine (hemocrine) ‘hormones’ represent the

level of hormone acting on most tissues distributed throughout the body.

18

Objective 5.

As you know from cardiovascular systems and neuroscience from this semester, not all
hormone molecules found in the blood can freely reach potential targets in tissue. For
example, the blood-brain barrier prevents many molecules present in the blood
supplying the brain to cross into the interstitial fluid surrounding the neurons within, as is
better described elsewhere. Other hormone molecules may be tightly bound to carrier
proteins and can therefore not leave the plasma.

For all those types of hormones which are not “endocrine”, but most particularly for
paracrine hormones, local concentrations around target cells are what matter. Since
these hormones both act very near their secretory cells and are typically metabolized
very quickly, plasma concentrations will have little to do with effective concentrations at
the target site. It is the interaction between hormone and receptor that matters in
producing effects regardless of how much or how little of that hormone is being carried
in the blood.

That said, for most water-soluble hormones that ARE classic endocrine hormones,
the amount in the plasma should be proportional to that in the fluid surrounding the
target cells.
Slide 19

Adaptation: Upregulation and Downregulation

• The goal is an
appropriate
response when the
hormone is present.

• Up-regulation
increases receptor
number, leaving
cells able to
respond to even low
levels of hormone

• Down-regulation
prevents
overstimulation in
excess of hormone
19

Objective 5.
“Cells can adjust their sensitivity to a signal by adaptation or desensitization, whereby
prolonged exposure to a hormone decreases the cell’s response over time. Adaptation
allows cells to respond to CHANGES in hormone levels rather than to absolute levels.
Adaptation is a reversible process that can involve a reduction in the number of
receptors expressed in the plasma membrane, inactivation of receptors, and changes in
signaling proteins mediating the downstream effect of the receptors.”
Note that it does not matter whether the actual receptors are supposed to be on the cell
surface (for water-soluble hormones) or intracellular (for lipid-soluble hormones). What
matters is whether the hormone is always present-- in which case down-regulation will
occur (e.g. syndrome of inappropriate antidiuretic hormone or SIADH) --or almost never
present-- in which case up-regulation will occur (e.g. insulin receptors in untreated Type
1 diabetes mellitus).
For this reason, physiologic hormone secretion patterns that are episodic or pulsatile
normally provide enough signals that the optimal number of receptors are always
present, because then cells can respond appropriately when hormone levels rise and
then cease this response when hormone levels fall.
This concept is most generally covered in the context of pharmacologic agents that
induce downregulation (e.g. nicotine in smoking), but the same principles apply to
physiology and pathology.
Slide 20

• Water-soluble hormones are easy to transport but

they require second messenger systems because
they usually can’t cross into cells. Hormone Transport
– They typically disappear quickly from the blood,
with a half life of seconds to minutes.
– Certain exceptions (e.g. growth hormone) that
also bind to transport proteins take longer to
disappear from the blood.

• Water-insoluble hormones are generally not

dissolved in the plasma.
– They require transport proteins to move them
through the body.
• Transport proteins include albumin and
Thyroid hormone-Binding Globulin (TBG)

– However, once they reach a target tissue, they

can readily enter the cell and bind to receptors
within.

– The more tightly hormones bind to transport

molecules, the longer are their half-lives.
– Lipid soluble hormones have half lives of as
little as 30 minutes for aldosterone to as much
as 7 days for thyroxine (thyroid hormone T4). 20

Objective 6.

Two notable exceptions to the rules above are Growth Hormone (GH) and Insulin-like
Growth Factor 1 (IGF-1). Each of these hormones has a specific transport protein,
unlike most water-soluble hormones, so they will have half-lives that are somewhat
longer than most other water-soluble hormones.

SUPPLEMENTAL Information: Aldosterone half life

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.1987.tb02948.x/full
Slide 21

Hormone Disposal-- Overview

• Hormones need to be temporary so that their effects end when these
effects are no longer needed.

• Removal of hormone is therefore as important as secretion of hormone

• The metabolic clearance rate (MCR) is the volume of plasma cleared of a

hormone per unit time.

– Usually expressed as mL/min.

– MCR is inversely related to half-life, the faster the clearance rate,

the shorter the half-life of the hormone in the plasma.

– In general water-soluble hormones, which usually don’t have specific

transport proteins, have greater MCRs than do lipid-soluble hormones.
– The kidney and liver are major sites for hormone extraction and
degradation. Breakdown products can appear in the urine or the bile.
– Target tissues also can degrade many hormones. 21

Objective 6.

Quote: “Two factors can increase or decrease the concentration of a hormone in the
blood. One factor is the rate of hormone secretion into the blood. The second is the
rate of removal of the hormone from the blood, which is called the metabolic clearance
rate and is usually expressed in terms of the number of milliliters of plasma cleared of
the hormone per minute.”

Clinical relevance: if you have two hormones and one is metabolized faster than the
other, its clearance will be greater than the other. This first hormone’s half-life will be
proportionally shorter because it will take less time to clear (clean) exactly 50 percent of
the plasma. This knowledge is a tool you will keep in your kit when evaluating patients
with clearable poisons in their blood, when giving dosages and routes of administration
for drugs that have different half-lives, and for evaluating whether metabolism of a given
hormone is working correctly in diagnosing or treating a clinical endocrinology condition.

Note: Technically one can separate clearance secondary to urinary excretion from
clearance secondary to metabolism at target tissues but for this module we are lumping
them together into a widely-used generic concept of the MCR, because the specific
route of exit from the plasma is less important than how fast the overall exit occurs.
Supplemental: In pharmacology, these two routes are sometimes discussed separately.
You will see these more in Foundations 2 in Dr. Babbini’s lectures.

I shall ask NO questions on calculating clearance as is done in renal physiology.

It is the concept that is important in endocrine physiology.
Slide 22

General Rules Involving Hormonal Half-lives

1) Locally-acting biomolecules are often metabolized by locally-produced
degrading enzymes and therefore exhibit a short half-life.
• e.g. vasoconstrictors degraded by endopeptidases
2) Small peptides typically act locally and exhibit the shortest half-lives.
3) Hypothalamic hormones exhibit relatively short half-lives.
4) Hydrophilic biomolecules exhibit shorter half-lives than hydrophobic
biomolecules.
• Hydrophobic hormones typically bind to serum proteins which extends
half-life.
5) Prohormones and break-down metabolites exhibit a longer half-life than
the most active biomolecule/hormone.
• e.g. T3 (the more bioactive thyroid hormone) has a shorter half-life
than T4 (the hormone found in higher quantities)

22

Objective 6.

Again, note the two pairs of exceptions to the rules.

• Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1). Each of these
hormones has a specific transport protein, unlike most water-soluble hormones, so
they will have half-lives more typical of lipid-soluble molecules (several hours).
Some sources differ on this, however, but even for those the half-life of GH is longer
than that of the other classic peptide hormones.
• Most amine hormones are water soluble, so they have very short half-lives, rivalling
those of the very smallest peptides (e.g. epinephrine is close to that of oxytocin, and
both are metabolized and removed faster than prolactin). But two “amine
hormones”, the T3 and T4 variants of thyroid hormone, are lipid soluble and they
have the longest half-lives of all of the classic endocrine hormones, by a wide
margin.
Slide 23

The half-life of common biomolecules:

Biomolecule Half-life
Angiotensin II ~2 min Predominantly
locally-acting
Endothelin-1 ~2 min biomolecules, with some
Epinephrine ~2 min water-soluble endocrine
hormones
Prostaglandins ~ 2 min
Insulin ~ 3 – 5 min Episodic release!
Growth hormone 18 - 24 min
Aldosterone ~30 min
Cortisol ~ 60 – 90 min Predominantly lipid-soluble
Progesterone 12 – 16 hrs. endocrine hormones.
Transported in circulation
Triiodothyronine (T3) 16 – 24 hrs. bound to binding proteins.
Thyroxine (T4) ~ 7 days
23

Objective 6.
Modified from source: https://quizlet.com/128772064/intro-to-endocrinology-flash-cards/
This is a very short list that includes relatively more lipid-soluble hormones while not
listing the majority of water-soluble autocrine, paracrine, and endocrine substances.
Generally speaking, those molecules designed for secretion and distribution by the
paracrine route tend to have some of the shortest half-lives because their
degradation/reuptake mechanisms are also right there with the secretory and target
cells. The molecules that need to enter the bloodstream might be slightly slower since it
takes a longer time to get a biologically active concentration up in the plasma compared
to a very small volume of fluid surrounding a paracrine secretory cell, and because
transport is more complex, the hormones must physically enter the blood for transport,
maybe bind to a carrier molecule, then leave the blood prior to affecting a target cell.
• Growth hormone will be discussed further in Hypothalamic-Pituitary Physiology.
Sources vary as to its half-life, independent of binding proteins the shortest half-lives
mentioned are 8-12 minutes but because of binding proteins it can take up to 12-14
hours to clear half of the blood of fully bound growth hormone. There is more
consensus around a half-life just over 20 minutes than any other, so it is listed
as such in this table. At a minimum its half-life is still longer than almost all
other water-soluble amine or peptide hormones and shorter than almost all
other lipid-soluble steroid or steroid-like hormones.
https://www.ncbi.nlm.nih.gov/pubmed/11743895