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Title: Morphological and functional correlations in normal and neoplastic tissues
Author: Grigor, Kenneth McNeill
ISNI:       0000 0001 3520 8061
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1979
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This thesis deals with experimental aspects of morphological and functional correlations at the histological and biochemical levels in various normal and neoplastic tissues. A physiological section examines functions and effects of the normal foetal testis, and a clinicopathological section is concerned with morphological and functional features of testicular and adrenocortical neoplasms. The normal foetal testis. The foetal testis is hormonally active, producing androgenic steroids which cause masculinisation of the sex ducts and urogenital sinus: and a separate Mullerian inhibitory factor (MIF) which actively suppresses the female sex duct. MIF is not a steroid molecule in free form, and at least part of it is a protein. I set up an organ culture bioassay system to study aspects of Mullerian duct inhibition. Foetal rat genital tracts, containing Mullerian and Wolffian ducts, were explanted from foetal rats and maintained in organ culture for 3 days. The development of gonads and sex ducts in vitro followed the normal in vivo pattern. The Wolffian ducts were stabilised by androgens, by autologous or homologous foetal rat testes, and by heterologous human foetal testes. The Mullerian ducts regressed in the presence of autologous, homologous or heterologous foetal testes. On theoretical grounds, I wondered if foetal testicular progesterone, probably attached to a carrier protein analogous to the androgen binding protein produced by the adult testicular Sertoli cells, may be involved in Mullerian duct inhibition. Addition of progesterone to the culture medium did cause Mullerian duct regression, but it was difficult to be certain that this was a specific physiological effect rather than a non-specific cytotoxic effect. Progesterone was also found to stabilise the Wolffian duct in organ culture. Substantiation of the possible physiological role of foetal testicular progesterone necessitated verification that the foetal testis is capable of progesterone production and secretion. This was attempted using monolayer cultures of rat foetal testes maintained with and without trophic hormonal stimulation. The endogenous steroid production and secretion was determined by radioimmunoassay (RIA) for progesterone and testosterone, and by high pressure liquid chromatography (HPLC) which could efficiently separate, identify and quantitate 47 different standard steroid molecules. A testosterone RIA had been established in our laboratory, and I developed a similar assay for progesterone paying particular attention to precision, sensitivity, specificity and choice of method for separating free and bound labelled progesterone. HPLC was used to examine the profile of steroids secreted by the foetal testicular cells in monolayer culture. Foetal testes secrete testosterone and progesterone in monolayer culture. Testes from 14½ day foetal rats initially failed to produce significant amounts of steroid hormone in vitro, but after cyclic AMP stimulation substantial amounts of progesterone were identified. Testes from older foetal rats initially produced testosterone in greater amounts than progesterone in culture, but after a few days testosterone, then progesterone, output fell to baseline levels. Steroidogenesis was occasionally reactivated by human chorionic gonadotrophin stimulation, but a greater, more consistent reactivation was effected by cyclic AMP, progesterone production being evident before testosterone. The results indicate that the foetal testis may produce progesterone at a time when it is known to produce the Mullerian inhibitory factor. Later in gestation, secretion of MIF diminishes, and output of androgens increases I postulate that this may be due to conversion of progesterone to testosterone. Definite proof of this hypothesis is still lacking. I conclude from the section on experiments with normal animal tissues that the histological features of foetal testes give no indication of the pattern of steroidogenesis, and that the cytological appearances of foetal testicular cells in monolayer culture do not alter with changing functional activity. The histological regression of Mullerian ducts in organ culture is morphological evidence of the presence of MIF, but it is not truly specific. The remainder of this thesis concerns neoplastic tissue with secretory potential, and the morphological patterns associated with various secretory products.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available