Human Physiology, 14th edition (2016)

320 Chapter 11

whose thyroid is deficient (who are hypothyroid). By contrast,

polypeptide and glycoprotein hormones cannot be taken orally

because they would be digested into inactive fragments before

being absorbed into the blood. Thus, insulin-dependent diabetics

must inject themselves with this hormone.

Polar, water-soluble hormones include polypeptides, gly-

coproteins, and the catecholamine hormones secreted by the

adrenal medulla, epinephrine and norepinephrine. These hor-

mones are derived from the amino acid tyrosine (see chapter 9,

fig. 9.8). Thus, like the polypeptide and glycoprotein hormones,

the catecholamines are too polar to pass through the phospho-

lipid portion of the plasma membrane. The hormone secreted

by the pineal gland, melatonin, is different; derived from the

nonpolar amino acid tryptophan, melatonin pills can be effec-

tive because (like steroids and thyroxine) this hormone can pass

through plasma membranes. Melatonin, however, also has some

similarities to the polar hormones in terms of its effects on cells.

Prohormones and Prehormones

Hormone molecules that affect the metabolism of target cells are

often derived from less active “parent,” or precursor, molecules.

In the case of polypeptide hormones, the precursor may be a lon-

ger chained prohormone that is cut and spliced together within

the gland cell to make the hormone. Insulin, for example, is pro-

duced from proinsulin (see fig. 3.23) within the beta cells of the

islets of Langerhans of the pancreas. In some cases, the prohor-

mone itself is derived from an even larger precursor molecule; in

the case of insulin, this molecule is called preproinsulin.

In some cases, the molecule secreted by the endocrine

gland (and considered to be the hormone of that gland) is actu-

ally inactive in the target cells. In order to become active, the

target cells must modify the chemical structure of the secreted

hormone. Thyroxine (T 4 ), for example, must be changed into

T 3 within the target cells in order to affect the metabolism of

these cells. Similarly, vitamin D 3 secreted by the skin must be

converted into 1,25-dihydroxyvitamin D 3 to be active in its tar-

get cells. Testosterone is an active hormone in its own right,

but in some target organs it must be converted into dihydrotes-

tosterone (DHT) or other derivatives to be active ( table 11.3 ).

In this text, the term prehormone will refer to molecules like

and figure 2.6.) Because the nonpolar hormones are soluble
in lipids, they are often referred to as lipophilic hormones.
Unlike the polar hormones, which cannot pass through plasma
membranes, lipophilic hormones can gain entry into their tar-
get cells. These lipophilic hormones include the steroid hor-
mones and thyroid hormones.
Steroid hormones are secreted by only two endocrine glands:
the adrenal cortex and the gonads ( fig. 11.2 ). The gonads secrete
sex steroids; the adrenal cortex secretes corticosteroids (includ-
ing cortisol and aldosterone) and small amounts of sex steroids.
The major thyroid hormones are composed of two deriva-
tives of the amino acid tyrosine bonded together ( fig.  11.3 ).
When the hormone contains 4 iodine atoms, it is called tetraiodo-
thyronine ( T 4 ), or thyroxine. When it contains 3 atoms of iodine,
it is called triiodothyronine ( T 3 ). Although these hormones are
not steroids, they are like steroids in that they are relatively small,
nonpolar molecules. Steroid and thyroid hormones are active
when taken orally (as a pill). Sex steroids are the active agents in
contraceptive pills, and thyroid hormone pills are taken by people

Figure 11.3 Structural formulas for the thyroid
hormones. Thyroxine, also called tetraiodothyronine (T 4 ), and
triiodothyronine (T 3 ) are secreted in a ratio of 9 to 1.

Thyroxine, or tetraiodothyronine (T 4 )

Triiodothyronine (T 3 )

HO O CH 2

NH 2

CH C

O

OH

HO O CH 2

NH 2

CH C

O

OH

Endocrine Gland Prehormone Active Products Comments

Skin Vitamin D 3 1,25-Dihydroxyvitamin D 3 Conversion (through hydroxylation reactions) occurs

in the liver and the kidneys.

Testes Testosterone Dihydrotestosterone (DHT) DHT and other 5a-reduced androgens are formed in

most androgen-dependent tissue.

Estradiol-17b (E 2 )E 2 is formed in the brain from testosterone, where it is

believed to affect both endocrine function and

behavior; small amounts of E 2 are also produced in

the testes.

Thyroid Thyroxine (T 4 ) Triiodothyronine (T 3 ) Conversion of T 4 to T 3 occurs in almost all tissues.

Table 11.3 | Conversion of Prehormones into Biologically Active Derivatives