Steroid Hormones 101
steroid hormones bound to carrier proteins
Introduction to steroid hormones
The steroid hormones have the following structure
as their nucleus:
Steroid hormones are a subset of hormones
derived from cholesterol
Small, non-water soluble
molecules that must be transported in the blood bound to a protein serum
globulin - Some hormones are transported by
specific transport proteins, for example, sex hormone binding globulin (SHBG)
binds and transports TESTOSTERONE and
Being fat-soluble, they
can easily pass through the cell membrane –
can then combine with a protein receptor in either the cytoplasm or nucleus,
depending on the hormone, to cause changes within the cell.
, ESTRONE, ESTRIOL
+ Vitamin D
Refers to # of carbons in molecule
** Qualify as hormones, since they are:
(a) made in certain cells, (b) carried in
the blood (c) affect gene
transcription in target cells; technically they are sterols not steroids
Steroid Hormone Production
Where are steroid hormones produced?
steroid hormones are secreted by the ovaries (ovarian follicle
/Corpus luteum), testes, prostate,
and adrenal cortex - in addition,
further conversions, break-downs and secretions occur in the liver, extragonadal sites (E.g. adipose tissue, skin
fibroblasts, bone, placenta , other target tissues).
How Does the Body make Steroid Hormones?
are synthesized as needed using cholesterol (mostly stored intracellularly in the tissue of origin)
as the ultimate precursor , in response to appropriate
(Luteinizing Hormone-stimulated signal transduction - the intracellular biochemical
reactions that occur after stimulation of the LH membrane-bound receptor up
until the initiation of cholesterol transport to the mitochondria) -
the precursor is moved from storage depots to the mitochondria and smooth
endoplasmic reticulum, where a series of enzymes (E.g, isomerases,
dehydrogenases) rapidly convert the molecule to the appropriate steroid hormone.
The identity of the
final hormone is determined by the specific enzymes expressed in the tissue
Limiting factor for
steroid hormone secretion is the rate of production -
hormones require a stimulus for production, but once synthesized, their
release occurs by passive diffusion.
Steroid hormones are not stored -
in contrast to the
amines (e.g. thyroid hormones – THYROXINE (T4),
Triiodothryronine (T3)) , catecholamines (E.g.
epinephrine, norepinephrine) and
polypeptide hormones (e.g. pituitary ACTH,
parathyroid hormone), steroid hormones are not packaged for
storage for later use.
Steroid hormone availability is thus dependent on their
continual biosynthesis -
to enable secretion to occur when needed for a
physiological response or developmental change to occur.
What affects steroid production
Any chemical interference to
steroidogenesis can cause adverse effects to the reproductive system - e.g.,
altering enzymatic activity or hormone production, altering precursor
availability, interfering with control mechanisms, etc.
Steroidogenesis of sex hormones
Chronic stress, disease or nutritional status -
secretion and activity of a
particular hormone may be adjusted upward or downward in response to challenges
such as chronic stress, disease, or a
(excess sugar / refined starches, trans-fatty
acids, lack of needed nutrients such as
omega-3 fats, a full range of
essential amino acids, vitamins, minerals,
Cholesterol availability -
a constant supply of cholesterol is necessary
for enzyme-catalysed steroid hormone production since they are
manufactured on an “as needed” basis - unlike
protein/polypeptide hormones, steroid
hormones are not stored in large amounts - one of several reasons for
not being too eager to lower your cholesterol levels.
StAR (Steroid Acute Regulator) protein transports
cholesterol from the outer to the inner mitochondrial membrane - a rate-limiting
step of steroidogenesis -
carried between the membranes by the StAR protein and
steroidogenesis is controlled through regulation of its production.
(Steroid Acute Regulator) Gene
Factor-1) regulates the basal and hormone-stimulated expression of the StAR
gene, which codes the StAR protein
that transfers cholesterol into mitochondria.
▲ Also upregulating the
StAR gene and thus enhancing steroid
GROWTH HORMONE, ESTRADIOL,
StAR pathway directly affected by:
barbiturates, Lindane, DBA (byproduct of
water disinfection using chlorine), Dimethoate, Diethylumbelliferyl phosphate,
Most circulating steroid hormones are bound to
steroid hormone binding carrier proteins
make them water-soluble in the blood, most steroid hormones are bound to carrier
proteins, and only a small fraction
circulates “free” or unbound -
A rapid equilibrium exists between
protein-bound and unbound steroid in
(enveloped by specific globulins or
when steroid hormones circulate
through the liver, they eventually become protein-bound a process that not only
impedes their bio-availability but also
makes them water soluble, thus facilitating their excretion in urine.
NOTE: Measuring the concentration of these NON-bio-available forms in
urine or serum is irrelevant since it provides no clue as to the concentration
of the more clinically significant “free” (bio-available) hormone in the blood
binds many steroids fairly loosely;
hormones have specific binding globulins
Sex Hormone Binding Globulin (SHBG)
Corticosteroid Binding Globulin (CBG) for PROGESTERONE,
CORTISOL (and other corticosteroids);
For more details:
Sex hormone-binding carriers
Unbound / “Free” –
presumed to be the biologically active fraction available for entering targets
through their lipid bilayer.
Steroid hormones carry their
message to cells by leaving the blood flow at capillaries to enter cells where
they bond with specific hormone receptors.
Saliva testing is far
superior to blood or urine testing in measuring “free” bio-available hormone
when circulating through saliva glands, the “free” non-protein-bound steroid
hormone (whether in RBCs or serum)
diffuses easily from blood capillaries into the saliva gland and then into the
mucins of saliva. Protein-bound, non-bio-available hormones do not pass into or
through the saliva gland
Steroid hormones act on
target cells via receptors located in the cell interior
The primary function of steroid hormones is to
affect an alteration in the rate of
transcription of specific genes in target cells, by either increasing or
decreasing their expression -
hormone usually diffuses through the plasma membrane, through the cytoplasm and
into the nucleus, where it binds to a receptor protein. In turn, this activates
a portion of DNA that turns on specific genes.
There are several classes of steroid receptors -
those for glucocorticoids, mineralocorticoids,
progestagens, etc. Steroid receptors comprise
a family of related proteins that also show homology to receptors for the
thyroid hormones and vitamin D.
The receptor has regions or domains that carry
out specific tasks:
recognition and binding of the steroid
binding to a specific region on chromosomal DNA
A third for
helping regulate the transcriptional complex.
Steroid action is relatively slow in onset (hours) - but may
be long lasting because of the duration of production and half-lives of the
messenger RNA and proteins induced in target cells.
Excretion in the urine, bile or feces –
steroid hormones that are excreted in the bile may be hydrolyzed in
the G.I. tract and then reabsorbed back into the body through the portal system
Steroids in the blood are eliminated by
metabolism in the liver – where reduced forms are produced and subsequently conjugated to
glucuronic acid and sulfate. These metabolites are freely soluble in blood and
are eliminated from the body via the kidneys and the GI tract.
Small amounts of free steroid hormone are also
directly excreted by the kidneys