GnRH agonists have a number of clinical uses. They induce ovulation and
spermatogenesis, increasing gonadotropin and sex-steroid levels. Therefore, GnRH
agonists can be used to treat both male and female infertility. Paradoxically, they also
inhibit spermatogenesis in rats after repeated administration over a prolonged period,
thus allowing the potential for decreasing male fertility without decreasing libido; this
means that GnRH analogs can be used either to increase or to decrease fertility in men
or women. In addition to the treatment of fertility disorders, GnRH agonists can be used
to treat prostate cancer, uterine fibroids, endometriosis, and polycystic ovary syndrome.
Gonadoliberin antagonists can be obtained by modifying the first three amino acids
of the natural peptide. The N-terminal is considered the active center, whereas the rest
of the molecule serves only in the binding process. The [D-Phe^2 ,Pro^3 , D-Trp^6 ],
[D-pyro-Glu^1 , D-Phe^2 , D-Trp^3 , D-Trp^6 ] and similar compounds can block ovulation at
doses of 200 to 750 μg.
5.15.2.4 Somatocrinin (Growth Hormone Releasing Hormone)
Thegrowth hormone releasing hormone(orfactor) (GHRH; somatocrinin) was isolated
only in 1982. It consists of either 40 or 44 amino acids. In addition to stimulating growth
hormone production it also stimulates release ofsomatomedins, which are responsible
for the many anabolic effects of growth hormone. Its production by recombinant DNA
techniques has made it possible to undertake physiological studies on its activity.
Growth hormone releasing peptides(GHRPs) are small synthetic peptide analogs of
GHRH that stimulate GH secretion. Sermorelin (5.75, GHRH1-29) is a clinically avail-
able acetate salt of the synthetic 29-amino acid N-terminal segment of GHRH. Even
shorter peptide fragments have biological activity. GHRPs, such as sermorelin, may be
used diagnostically to evaluate pituitary function in children with short stature, and may
be used therapeutically to promote growth in children with short stature arising from a
neuroendocrine dysfunction. Although GHRPs have not been clearly shown to cause
malignancies, their capacity to induce long-term carcinogenesis is a theoretical possi-
bility that has not been fully studied. Interestingly, GHRH antagonists have been shown
to reduce the growth rate of human malignancies in nude mice.
HORMONES AND THEIR RECEPTORS 343