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Title: Studies on induced ovulation as a basis for gonadotrophin assay
Author: Wells, Michael
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1968
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A brief outline is presented of the general principles underlying biological assay, and of the methods currently available for the assay of human pituitary genadotrophins. The literature on induction of ovulation in laboratory animals and its application to bioassay is reviewed, up to the description by Cunningham (1962) of a practicable assay method baaed on the induction of ovulation in immature mice. The general techniques used by the author for the performance of the Cunningham ovulation assay are described, as are the statistical methods employed in the occupation of aasay results. Optimum conditions for the perfomance of the ovulation assay were found to be similar to those described by Cunningham with regard to dosage and timing and the probit transformation of the percentage of mice ovulating appeared to be the most suitable measure of response. The ovulation assay was found to have a wide field of application valid assay of good precision being obtained for a variety of gonadotrophins of human and animal origin. The sensitivity of the assay was such as to make it suitable for application in clinical research. 2 Results of experiments using purified FSH and LH, and using mixtures of gonadotrophins, indicated that the assay was not specific for LH. The administration of a barbiturate and of other drugs which suppress pituitary function frequently reduced the sensitivity of the assay, but did not appear to alter its specificity, and it was concluded that while the presence of endogenous gonadotrophins probably played a part in the ovulatory response it was apparently not wholly responsible for the lack of specificity of the assay. Hypophysectomy completely abolished the response to both PMS and HCG effect on specificity could not be assessed. Part of the reduction in sensitivity following Hypophysectomy was probably due to the stress of operation. The use of HCG instead of PMS for priming the animals did not improve specificity. The role of the gonadotrophins in the control of the human menstrual cycle is discussed, and an outline is given of the relevant literature. The ovulation assay was applied to the measurement of urinary gonadotrophin during a series of 7 cycles from 4 normal women and slowed elevated levels near to mid-cycle in every case. In 2 of the subjects urinary gonadotrophin was measured in cycles during which an oral contraceptive was taken and the "peak" in excretion observed in the normal cycles was found to be absent. In a further study of the effect of an oral contraceptive, the mean daily urinary excretion of gonadotrophin during a 4~day period near mid-cycle was measured in a series of 8 normal women before and during a course of contraceptive tablets. This treatment reduced gonadotrophin excretion in 7 of the subjects, while in the eight, the assay was invalidated by slope variation. It was concluded that the oral contraceptive exerted its effect at least partly by suppressing pituitary gonadotrophin secretion. The results arc discussed with reference to the findings or other workers using; different assay methods. In an investigation of the relative efficiency of a number of established methods for the extraction of gonadotrophin from human urine, the method of Johnsen (1958) employing tannic acid precipitation was found to give consistently high yields end also extracts of high specific activity. The methods were compared by the ovulation assay and also by the mouse ovarian augmentation assay for FSH. Inhibition of the response to gonadotrophins by heat- inactivated urinary extracts noted by several workers using the mouse uterus assay was shown to occur also in the ovulation assay. There was some evidence of selective inhibition of the response to HGC compared with that to PMS. Inhibition of the ovulatory response was usually accompanied by a reduction of the body weights of the mice, and this reduction was shown to be related to the dose of inhibitor. It was concluded that the inhibitory effect of the extracts tested was due at least in part to general toxicity, although the results obtained did not exclude the possibility that an additional specific inhibitor of gonadotrophin might also be present.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available