Since the early 1900's, many investigators have studied the effects of pituitary
ablation and the mode of action of the hypophyseal hormones. Initially, work was
mainly directed towards the purification and bioassay of the various hormones, although
the effects of hormone administration were also studied. Recently, attempts have been
made to synthesise some of the hormones. The aim of this thesis is to describe a
series of studies undertaken in an attempt to develop new assay methods for growth
hormone and the gonadotropins and the application of these procedures. (89)
An investigation of the bioassay for growth hormone depending on the increase in
tibial epiphyseal cartilage width in immature hypophysectomised rats has shown that
the method is not specific and is of low sensitivity. The procedure has been used to
compare the potency of pituitary extracts from different species and to provide a
measure of the effect on body growth and on cartilage width of two synthetic compounds
and of nerve section. A dithiocarbamoylhydrazine derivative, Compound 33» 828 (I.C.I.)
was found to have a markedly inhibitory effect on general body growth and cartilage
width, possibly due to the toxicity of the compound. A synthetic polypeptide, Ciba
50920-Ba which is claimed to have an adrenocorticotrophic hormone-like action on the
adrenal, had no marked effect on cartilage growth. It has also been shown that the
artificial induction of muscular atrophy in young rats by section of the sciatic nerve
did not interfere with cartilage growth and that the administration of pituitary hormones
to animals treated in this way was without effect. (166)
A haemagglutination-inhibition method has been developed for the assay of growth
hormone and has proved to be sensitive and highly specific. When estimates of the
growth hormone potency of standard pituitary preparations were made by both the bioassay
described above and the immunological method, similar results were obtained. The
immunological procedure was, however, found not to be sufficiently sensitive for
clinical application. A latex particle agglutination-inhibition method for the
quantitative determination of human chorionic gonadotrophin has also been developed. This again proved to be unsuitable for clinical application. (88)
The pyruvic acid oontent of the immature rat ovary, both prior to and following
gonadotrophic stimulation, was estimated by two different methods. A marked rise in
pyruvic acid was noted following initial stimulation with pregnant mare serum
gonadotrophin, but this rapidly fell to a low level which could not be altered by
further gonadotrophic stimulation. The relationship between pyruvic acid and
gonadotrophic stimulation is discussed. (65)
The studies reported in this thesis have shown that the methods available for the
quantitative determination of growth hormone and gonadotrophins axe not entirely
satisfactory because of poor sensitivity or lack of specificity. However, despite
these limitations, useful information can be obtained by these procedures although it
is clear that they are not suitable for clinical application. The development of more
sensitive and specific methods for the estimation of these hormones is therefore
necessary and it is suggested that future work in this field should be directed
towards this end