Human Physiology, 14th edition (2016)

692 Chapter 19

Estrogen and Testosterone

Another hormone needed for the regulation of the skeletal sys-

tem is estrogen. In both men and women, estrogen is needed

for the epiphyseal discs (the cartilage growth plates) to seal

(become bone). This estrogen comes from the ovaries via

the circulation in women, but it is formed within the epiphy-

seal discs from circulating testosterone in men. (As may be

recalled from chapter 11, estradiol is derived from testoster-

one; see fig. 11.2.) Also, proper bone mineralization, and the

prevention of osteoporosis, requires the action of estrogen in

bone. Men are less prone to osteoporosis than postmenopausal

women because men can form estrogen (derived from circu-

lating androgens) in their bones, whereas in women, estrogen

secretion from the ovaries declines at menopause. Men with a

genetic deficiency in aromatase (the enzyme that converts tes-

tosterone to estradiol) have the reduced bone mass characteris-

tic of osteoporosis.

Estrogen promotes bone mineralization partly because

it stimulates the actions of osteoblasts. As mentioned previ-

ously, osteoblasts secrete new bone matrix and also produce

molecules—RANK ligand (RANKL) and osteoprotegerin—

that regulate osteoclast production. Estrogen affects this reg-

ulation and by that means suppresses the formation of new

osteoclasts and promotes the apoptosis (cell suicide) of exist-

ing osteoclasts. In summary, estrogen promotes bone miner-

alization by stimulating bone deposition by osteoblasts and

inhibiting bone resorption by osteoclasts.

Calcium is also needed to maintain proper membrane per-
meability. An abnormally low plasma calcium concentration
increases the permeability of the cell membranes to Na^1 and
other ions. Hypocalcemia, therefore, enhances the excitability
of nerves and muscles and can result in muscle spasm (tetany).
Unlike bone, articular cartilages that cover the bones at the
joints have little regenerative ability. By contrast to the numer-
ous osteoblasts and osteoclasts in bone, and the abundance of
stem cells in the periosteum and bone marrow, cartilage has
few cells and no blood vessels to supply nutrients. These are
supplied to the articular cartilages only by the synovial fluid.
As a result, damage to these cartilages due to injuries or age-
related changes does not heal well.

Hormonal Regulation of Bone

Parathyroid Hormone and Calcitonin

Whenever the plasma concentration of Ca^2 1 begins to fall, the
parathyroid glands are stimulated to secrete increased amounts of
parathyroid hormone (PTH) that work to raise the blood Ca^2 1
back to normal levels. As might be predicted from this action of
PTH, people who have their parathyroid glands removed (as may
occur accidentally during surgical removal of the thyroid) will
experience hypocalcemia. Hypocalcemia (low plasma calcium
concentrations) is a common clinical condition with many poten-
tial causes, including inadequate parathyroid hormone secretion
or activation of its receptors, insufficient vitamin D, insufficient
magnesium (needed for PTH secretion and action), and others.
Hypocalcemia can cause muscle twitching, spasms, severe tet-
any, cardiac abnormalities, and other symptoms.
Parathyroid hormone helps to raise the blood Ca^2 1 con-
centration through three mechanisms ( fig. 19.19 ):

1. PTH stimulates osteoclasts to resorb bone, thereby adding
   Ca^2 1 and PO 4 3 2 to the blood. This is the primary mecha-
   nism of PTH action.


2. PTH stimulates the kidneys to reabsorb Ca^2 1 , but acts to
   decrease the renal reabsorption of PO 4 3 2. This raises blood
   Ca^2 1 levels without promoting the deposition of calcium
   phosphate crystals in bone.


3. PTH stimulates the kidneys to produce the enzyme
   (1 a -hydroxylase) needed to convert 25-hydroxyvitamin
   D 3 into the active hormone, 1,25-dihydroxyvitamin D 3 (see
   fig. 19.21 ). This active form of vitamin D then promotes the
   absorption of Ca^2 1 and PO 4 3 2 from food and drink across
   the intestinal epithelium.
   Experiments in the 1960s revealed that high blood cal-
   cium in dogs could be lowered by a hormone secreted from
   the thyroid gland. This hormone, calcitonin, is secreted by the
   parafollicular cells and acts to inhibit osteoclast activity,
   thereby lowering the plasma Ca^2 1 concentration. As discussed
   in chapter 11, section 11.5, this effect is probably of negligible
   significance in normal human physiology. However, it is use-
   ful pharmacologically (as a drug) to inhibit bone resorption in
   people with stress factures of vertebrae due to osteoporosis (as
   discussed in the next Clinical Application box).

Figure 19.19 The negative feedback control of

parathyroid hormone secretion. A decrease in plasma Ca^2 1

directly stimulates the secretion of parathyroid hormone (PTH).

The production of 1,25-dihydroxyvitamin D 3 also rises when Ca^2 1

is low because PTH stimulates the final hydroxylation step in the

formation of this compound in the kidneys.

Decreased –

plasma

Ca2+ Negative

feedback

Parathyroids

PTH resorptionBone

Intestinal

absorption

Increased

plasma

Ca2+

Kidneys

Increased

1 α -hydroxylase

activity

25-Hydroxyvitamin D 3 1,25-Dihydroxyvitamin D 3

(from liver)

Sensor

Integrating center

Effector