Biology Reference
In-Depth Information
similar to Figure 9-4. It shows the blood serum levels of FSH, LH,
estrogen, and progesterone, and the events in the ovaries and uterine
lining during a menstrual cycle. Unfortunately, Figure 9-4 gives the
impression that hormone levels rise and fall smoothly on a timescale of
days, which is incorrect. Instead, pituitary hormones are produced in a
pulsatile manner; if they are not, the functions of the respective
endocrine signaling pathways will be inhibited. For instance, it has been
shown that the pulsatile nature of the GnRH signal is critical to its
function of stimulating LH and FSH release. Administering the peptide
as a nonvarying infusion not only fails to stimulate but, in fact,
diminishes the response. If a woman's LH and FSH levels remained
approximately steady over any given 24-hour period (as suggested by
Figure 9-4), she would be infertile. Therefore, clinicians have used
metering pumps to treat female infertility by administering GnRH in a
normal pulsatile pattern in order to restore the signal and subsequently
restore reproductive function.
A similar approach has been successful in cases of primary
hypothalamic failure, such as Kallmann syndrome or hypothalamic
amenorrhea, both of which are marked by a GnRH deficiency. The
technique has also been used to inhibit gonadotropin secretion by means
of long-acting, nonpulsatile GnRH analogues for the treatment of
prostate cancer, premature puberty, or endometriosis. In either case, the
pulsatile nature of the GnRH release is required for the pituitary to
respond normally. However, in the latter three examples, the
nonpulsatile GnRH will act to suppress the release of the gonadotropins
LH and FSH by the pituitary. This results in growth suppression in
prostate cancer, suppression of inappropriately early maturation in
premature puberty, and suppression of symptoms in endometriosis.
In summary, the GnRH-LH/FSH axis provides an impressive example
of how obtaining specific quantitative knowledge about hormone
secretion dynamics not only addresses important theoretical questions
about the signaling mechanism of the endocrine system, but also results
in successful therapeutic strategies. Children suffering from
premature puberty have been restored to a normal developmental
pattern, and previously infertile women have achieved normal
pregnancies.
The techniques outlined above require objective quantitative methods
for describing and comparing individual or multiple hormone
secretion profiles. In particular, it is necessary to have (1) an objective
definition of physiologically important properties of hormone
concentration dynamics, (2) formal techniques for quantification of these
aspects, and (3) standardized methods for comparison of hormone
secretion data. A major challenge, however, is the high complexity of
endocrine axes and the lack of sufficient direct experimental data.
Direct measurement of some hormones of interest is either
experimentally challenging or impossible, or unethical, especially in
