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Title: Paracrine mechanisms of gonadotrophin action on the ovary
Author: Smyth, Christopher David
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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This thesis describes a study of the role of local regulators in the modulation of gonadotrophin action. It was found that in vivo FSH stimulated granulosa cell proliferation and increased ovarian weight, but was incapable of stimulating granulosa cells to proliferate in vitro. This suggests that the action of FSH in vivo is mediated through another factor. However, in the presence of LH, FSH also stimulated the expression of differentiated functions (progesterone and oestradiol production) both in vivo and in vitro demonstrating a direct effect of FSH. In the absence of LH or aromatase substrate, FSH induced the potential for aromatisation but did not increase uterine weight, a marker of oestradiol production. Therefore it is concluded that FSH is the primary stimulus for follicular development but that LH is also required for co-ordinated follicular development. There is a growing body of indirect evidence to suggest that factors of FSH-stimulated granulosa cell origin may regulate adjacent thecal/interstitial cells. Cytochrome P45017α (17-hydroxylase/C17-20 lyase) in thecal/interstitial cells is a LH-responsive steroidogenic enzyme vital for androgen production. To obtain direct evidence for FSH-stimulated paracrine signalling in the ovary a rat thecal/interstitial cell culture system was validated for the study of the control of androgen production. Using this system and Northern hybridisation the control of androgen production by gonadotrophins and granulosa cell derived factors was studied. The ˜2.0 kb P45017α mRNA signal in ovarian total RNA from intact animals was dose-dependently increased by treatment with recombinant human FSH (rh-FSH). Treatment of hypophysectomised animals with rh-FSH did not consistently alter ovarian P45017α mRNA levels, though in the presence of low levels of LH, FSH increased P45017α mRNA expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available