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dc.contributor.authorHillier, Stephen Gilberten
dc.date.accessioned2018-01-31T11:21:28Z
dc.date.available2018-01-31T11:21:28Z
dc.date.issued1992en
dc.identifier.urihttp://hdl.handle.net/1842/26607
dc.description.abstracten
dc.description.abstractThis thesis comprises a series of published works arising out of research on the regulation of ovarian function undertaken by myself since receiving the degree of Ph.D. from the University of Wales in 1975. Eighty-three publications are submitted, reporting work that falls into three interrelated categories, as summarised below.en
dc.description.abstractBasic 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 gonadotrophs 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.en
dc.description.abstractBasic 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.en
dc.description.abstractApplied Clinical Studies Papers 57-83 deal with the practical relevance of ovarian endocrinology to the treatment of human infertility. Protocols for stimulating ovarian function in infertile women were evaluated, with monitoring based on serial measurements of ovarian steroids in blood and urine. Oocytes collected from such women were used for in-vitro fertilisation (IVF) and embryo transfer. Oocytes, granulosa cells and follicular fluids aspirated from IVF patients were studied to obtain information on steroid dynamics and other metabolic changes in ovarian follicles in relation to IVF outcome. Results highlighted the potential that endogenously produced steroids and exogenously administered steroid analogues have to interfere with human fertilisation, embryonic development and implantation. Alternative strategies are proposed for the induction of single or multiple ovulation (superovulation) in infertile women, based on the selective use of 'pure' FSH and LH to manipulate the ovarian paracrine system.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2017 Block 15en
dc.relation.isreferencedbyen
dc.titleRegulation of ovarian functionen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnameDSc Doctor of Scienceen


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