Therapeutic hormones - Pharmaceutical Biotechnology: Concepts and Aapplications - page 322

Urine Concentration Anion exchange

chromatography
(DEAE Sephadex)

Gel filtration
(Sephadex G-100)

Lyophilization

Figure 11.11 Overview of the procedure by which hCG may be purifi ed from the urine of pregnant females at labo-
ratory scale. Production-scale systems would be at least partially based upon such a purifi cation strategy. Although
initial concentration steps could involve precipitation, the use of ultrafi ltration would now be more common

Treatment typically entails daily i.m. administration of gonadotrophin, often for 12 days or
more, followed by a single dose of hCG. Alternatively, three equal larger doses of menotrophin
may be administered on alternate days, followed by hCG administration 1-2 days after the fi nal
menotrophin dose.
Gonadotrophins are also used in assisted reproduction procedures. Here the aim is to admin-
ister therapeutic doses of FSH that exceed individual follicular FSH threshold requirements, thus
stimulating multiple follicular growth. This, in turn, facilitates harvest of multiple eggs, which
are then available for in vitro fertilization. This technique is often employed when a woman has
a blocked fallopian tube or some other impediment to normal fertilization of the egg by a sperm
cell. After treatment, the resultant eggs are collected, incubated in vitro with her partner's sperm,
incubated in culture media until the embryonic blastocyst is formed, and then implanted into the
mother's uterus.
FSH and hCG also fi nd application in the treatment of male subfertility or related conditions.
Both are administered to males exhibiting hypogonadotrophic hypogonadism to stimulate sperm
synthesis and normal sexual function. hCG has found limited application in the treatment of pre-
pubertal cryptorchidism (a condition characterized by failure of the testes to descend fully into
the scrotum from the abdomen). The ability of this hormone to stimulate testosterone production
also caught the attention of some athletes, and, as a result, the International Olympic Committee
has banned its use.
The LH/hCG cell surface receptor is found in a number of non-gonadal tissues, indicating that
these hormones may exert physiologically relevant non-gonadal functions (Table 11.9). In ad-
dition, whereas liver, kidney and muscle cells are devoid of such a receptor, it is expressed by a
number of these tissues before birth, hinting at a potential developmental role. Receptor levels in
non-gonadal tissues are generally much lower than in gonadal tissue. hCG, therefore, probably has
a number of pregnancy/non-pregnancy-related non-gonadal functions that may give rise to future
additional clinical applications.

11.6.2 Recombinant gonadotrophins

Gonadotrophins are now also produced by recombinant DNA technology. The genes, or cDNAs
coding for gonadotrophins from several species, have been identifi ed and expressed in various