Human Physiology, 14th edition (2016)

710 Chapter 20

GnRH secretion. Androgens from fetal male testes apparently

suppress kisspeptin production to produce the noncyclical male

pattern of GnRH secretion.

Onset of Puberty

Secretion of FSH and LH is elevated at birth and remains rela-

tively high for the first six months of postnatal life, but then

declines to very low levels until puberty. Puberty is triggered by

the increased secretion of LH. Secretion of LH is pulsatile, and

both the frequency and amplitude of the LH pulses increase at

puberty (secretion is greater at night than during the day).

In animals such as rats and sheep, the low secretion of LH

prior to puberty is due to high sensitivity of the hypothalamus

to the negative feedback effects of gonadal hormones. The rise

in LH secretion at puberty is then caused by a declining sensi-

tivity of the hypothalamus to these negative feedback effects.

With less inhibition the secretion of GnRH rises, causing

increased secretion of LH (and FSH). However, this does not

seem to be the case for primates, including humans.

In humans, the increased secretion of GnRH occurs inde-

pendently of gonadal hormones. Puberty in humans is a result of

changes in the hypothalamus that allow an increased secretion

of GnRH to stimulate the pulsatile secretion of LH. Studies in

monkeys suggest that, prior to puberty, the secretion of GnRH

It appears that the frequency of the pulses of secretion, as well
as their amplitude (how much hormone is secreted per pulse),
affects the target gland’s response to the hormone. For example,
it has been proposed that a slow frequency of GnRH pulses in
women preferentially stimulates FSH secretion, while faster
pulses of GnRH favor LH secretion.
GnRH-releasing neurons are themselves capable of gener-
ating pulses of secretion. However, for optimal function, these
neurons must receive regulatory input from a number of neu-
rotransmitters and gliotransmitters. An essential excitatory input
is provided by neurons from other areas of the hypothalamus
that release kisspeptins, a family of neuropeptide transmitters.
This is shown by mutations that inactivate the kisspeptin recep-
tors on GnRH neurons, which drastically reduces GnRH secre-
tion and causes hypogonadism. Kisspeptins also affect the brain
during development, establishing the cyclical female pattern of

Figure 20.9 Interactions between the hypothalamus,

anterior pituitary, and gonads. Sex steroids secreted by

the gonads have a negative feedback effect on the secretion of

GnRH (gonadotropin-releasing hormone) and on the secretion

of gonadotropins. The gonads may also secrete a polypeptide

hormone called inhibin that functions in the negative feedback

control of FSH secretion.

Hypothalamus

GnRH

FSH LH

Gonadotropin

Inhibin

Gonads

Sex steroids

Gametes

(sperm or ova)

Anterior

pituitary

Sensor

Integrating center

Effector

CLINICAL APPLICATION

Endometriosis is the presence of endometrial tissue out-

side of its normal location, which is the inner layer (endo-

metrium) of the uterus. Called endometrial implants, this

tissue is formed from endometrial cells that enter the pelvic

cavity (probably by flowing backward through the uterine

tubes) and implant on the ovaries, outer layer of the uterus,

intestine, and other sites. Endometrial implants grow and

develop, and then bleed, like the normal endometrium

in response to the cyclic secretion of ovarian steroid hor-

mones (estrogen and progesterone; section 20.5). This can

cause inflammation, scar tissue, adhesions, and other prob-

lems that may produce intense pain and infertility.

Endometriosis is often treated with nafarelin ( Synarel ), a

GnRH analog that activates the GnRH receptors in the ante-

rior pituitary to stimulate FSH and LH secretion. However,

unlike the normal pulsatile secretion of GnRH, the stimula-

tion by nafarelin is intense and continuous. This causes a

downregulation of the GnRH receptors, producing a dras-

tic reduction in FSH and LH secretion. As a result, ovarian

steroid hormone secretion is reduced, stopping the growth

of both the endometrium and the endometrial implants and

illustrating the importance of the normal pulsatile secre-

tion of GnRH. These changes produced by nafarelin mimic

menopause, and may require replacement by birth control

pills containing low doses of estrogen and progesterone.

Clinical Investigation CLUES

Linda was diagnosed with endometriosis, for which she

received shots and birth control pills.

• What is endometriosis and what are its symptoms?


• What did the shots contain and how did they work?


• Why did she need to also take birth control pills?