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Title: Regulation of ovarian function
Author: Hillier, Stephen Gilbert
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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(i) Basic Experimental studies Publications 1-35 deal mainly with the use of cultured rat and marmoset monkey granulosa cells to study endocrine and paracrine mechanisms underlying gonadotrophin action on the ovaries. Primary cell cultures were used to define the roles of FSH and LH in controlling granulosa cell function and to assess the intrafollicular functions of sex steroids and putative nonsteroidal regulatory factors, such as inhibin. A particular contribution was the demonstration that androgens produced by thecal cells exert specific (receptor-mediated) modulation of granulosa cell differentiation - notably expression of aromatase, the enzyme uniquely responsible for oestrogen synthesis. Synthesis of inhibin and expression of messenger RNA species encoding inhibin and activin subunits in granulosa cells were also shown to be under gonadotrophic control and modulated by sex steroids, leading to the suggestion that the androgen/oestrogen and inhibin/activin axes of the ovarian paracrine system are functionally interlinked. (ii) Basic Clinical Studies Publications 36-56 are concerned with in vitro research on 'normal' ovarian tissues obtained from women undergoing elective surgical procedures. Techniques and experience acquired from experimental work on animal ovarian tissues were used to study the regulation of steroid hormone synthesis in human follicular and luteal cells. This work demonstrated that granulosa cells are primary cellular sites of oestradiol biosynthesis in the human ovary. It also confirmed the potential that theca-derived androgens have to modulate FSH-induced granulosa cell function, including aromatase activity and inhibin production. Conversely, androgen production by thecal cells was shown to be promoted by inhibin. Based on these findings it is postulated that an intrafollicular positive feedback loop exists mediated by theca-derived androgen and granulosa-derived inhibin, which may underpin preovulatory follicular 'selection' and oestrogen synthesis in the human menstrual cycle.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (D.Sc.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available