Biomedical Engineering Reference
In-Depth Information
targeting the pituitary, the inhibins/activins likely play a direct (mutually antagonistic) role as
paracrine/autocrine regulators of gonadal function.
They also likely induce responses in tissues other than the pituitary and gonads. In adults, for
example, inhibin is also synthesized by the adrenal glands, spleen and nervous system. Recent
studies involving inhibin-defi cient transgenic mice reveal a novel role for inhibin as a gonadal-
specifi c tumour suppressor. These mice, in which the α inhibin gene was missing, all developed
normally, but all ultimately developed gonadal stromal tumours.
11.6 Medical and veterinary applications of gonadotrophins
Because of their central role in maintaining reproductive function, the therapeutic potential of
gonadotrophins in treating subfertility/some forms of infertility was obvious. Gonadotrophins are
also used to induce a superovulatory response in various animal species, as outlined later. The
market for these hormones, though modest by pharmaceutical standards, is, none the less, substan-
tial. By the late 1990s the annual human market stood at about US$250 million, of which the USA
accounts for ∼US$110 million, Europe ∼US$90 million and Japan US$50 million.
11.6.1 Sources and medical uses of follicle-stimulating hormone, luteinizing
hormone and human chorionic gonadotrophin
Although the human pituitary is the obvious source of human gonadotrophins, it also constitutes
an impractical source of medically useful quantities of these hormones. However, the urine of
post-menopausal women does contain both FSH and LH activity. Up until relatively recently, this
has served as the major source used medically, particularly of FSH.
Menotrophin (human menopausal gonadotrophin) is the name given to FSH-enriched extracts
from human urine. Such preparations contain variable levels of LH activity, as well as various
other proteins normally present in urine. As much as 2.5 l of urine may be required to produce one
dose (75 IU,
7.5 mg) of human FSH (hFSH).
As mentioned previously, hCG exhibits similar biological activities to hLH and is excreted in
the urine of pregnant women. Traditionally, hCG from this source has found medical application
in humans (as an alternative to hLH; Figure 11.11).
In females, menotrophins and hCG are used for the treatment of anovulatory infertility. This
condition is due to insuffi cient endogenous gonadotrophin production. Menotrophin is adminis-
tered to stimulate follicular maturation, with subsequent administration of hCG to promote ovula-
tion and corpus luteum formation. Mating at this point should lead to fertilization.
Dosage regimes attempt to mimic as closely as possible normal serum gonadotrophin profi les as
occur during the reproductive cycle of fertile females. This is achieved by monitoring the resultant
oestrogen production, or by using ultrasonic equipment to monitor follicular response. Depend-
ing upon the basal hormonal status of the female, calculation of the optimal dosage levels can be
tricky. (Treatments are tailored to meet the physiological requirements of individual patients).
Overdosage can, and does, result in multiple follicular development with consequent risk of mul-
tiple pregnancy.
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