Assay of growth hormone and gonadotrophins in relation to clinical problems
Thompson, Helen Emma Christina Cargill
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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.