708
chapter30
Endocrine Metabolism I: Introduction
TABLE 30-3
Steroid-Binding Serum Proteins
Albumin
CBG1
TeBG2
Site of production
Liver
Liver
Liver
Molecular weight
6 6 , 0 0 0
58,000
94,000
Normal concentration
550 mM
710 nM
25 nM in men
40 nM in women
Cortisol-binding capacity
>200 mg/L
250 Mg/L
—
Testosterone-binding capacity
>400 mg/L
—
6
Mg/L
Estradiol-binding capacity
>3,000 mg/L
—
2
Mg/L
Steroid binding sites/molecule
> 1 0
1
1
Affinity (Kd)
~2 x 10
- 4
M (cortisol)
~4 x10
- 4
M
(testosterone)
3 x 10
- 8
M (cortisol)
~2 x 10
- 9
M
(testosterone)
Factors that increase
Glucocorticoids
Increased estrogens
Increased thyroid
concentration
Thyroid hormone
Increased thyroid hormone
hormone
Increased estrogen
(5-1 Ox)
Decreased androgens
Stress
Aging
High carbohydrate diet
Prolonged stress
Cirrhosis of liver
Factors that decrease
Hepatic disease
Increased glucocorticoids
Increased androgens (2x)
concentration
Renal disease
Protein malnutrition
Septic shock
Pernicious anemia
High carbohydrate diet
Obesity
Hyperprolactinemia
Increased GH
Menopause
Progestins
Glucocorticoids
'Corticosteroid-binding globulin (also called transcortin).
2
Testosterone-estradiol-binding globulin.
out of blood if it there were no means of rendering them
water-soluble. Two processes normally operate to solu-
bilize steroids in blood conjugation and protein binding.
Steroids that are conjugated, either with sulfate or glu-
curonic acid, are unable to enter target tissues because of
their water-soluble (hydrophilic) property; they are usu-
ally destined for excretion by the kidney. Although a few
tissues (e.g., placenta) have sulfatases that can liberate
a steroid from its sulfoconjugated state, most tissues are
lacking in this ability and are therefore unresponsive to the
high levels of conjugated steroids in the blood. The phys-
iologically important means by which steroid hormones
are solubilized for transport in blood is the use of cer-
tain serum proteins that solubilize steroids. The liver pro-
duces three serum proteins that serve to solubilize steroid
hormones (Table 30-3): albumin, a nonspecific adsorber
of hydrophobic substances that binds steroids with low
affinity; corticosteroid-binding globulin (CBG, also called
transcortin),
which binds C
21
steroids but has the great-
est affinity for cortisol; and testosterone-estradiol-binding
globulin (TeBG, also called
sex hormone-binding globu-
lin,
SHBG), which binds steroids of the androstane (C
1 9
)
and estrane (C|g) series but has greater specificity for an-
drogens than estrogens. Because of the high-affinity bind-
ing, steroids are not accessible for tissue uptake while
bound to either CBG or TeBG; therefore, the greater the
fraction of the steroid that is bound to these proteins, the
longer the half-life of the steroid. Unlike that of albumin,
the concentrations of CBG and TeBG in plasma are nor-
mally, near the concentration of the hormone they prefer-
entially bind, and each protein has only one steroid bind-
ing site per molecule. The CBG concentration in plasma is
