Morphological and functional correlations in normal and neoplastic tissues

Grigor, Kenneth McNeill (1979) Morphological and functional correlations in normal and neoplastic tissues. MD thesis, University of Glasgow.

Abstract

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 v/as 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 14

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: A Munro-Neville
• Keywords: Biochemistry, Histology
• Date of Award: 1979
• Depositing User: Enlighten Team
• Unique ID: glathesis:1979-73164
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73164