Androgen synthesis, metabolism and action in the developing ovarian follicle

Lebbe, Marie (2016). Androgen synthesis, metabolism and action in the developing ovarian follicle. University of Birmingham. Ph.D.

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Abstract

The ovarian follicle is the major site of sex steroid production in females, hormones that are crucially required for normal ovarian function and female reproduction. The biosynthesis and metabolism of androgens by individual follicles throughout development has been difficult to study because androgens and androgen precursors are structurally similar molecules present in low concentrations. Androgens have dual dose-dependent effects on folliculogenesis, with reduced or exaggerated levels of androgens being deleterious for follicle development. Few studies have shown the whole spectrum of androgen action using a single experimental model.
Here we employed tandem mass spectrometry to measure sex steroid production by murine follicles, cultured in an alginate encapsulated, 3-dimensional model. We showed developmental stage-dependant FSH-stimulated androgen and oestrogen secretion. When follicles were cultured in the presence of non-aromatisable 5-dihydrotestosterone, endogenous androgen production decreased. Following exposure to the universal sex steroid precursor dehydroepiandrosterone, high androgen generation was achieved by immature follicles. We described androgen receptor-mediated growth-promoting effects of androgen supplementation in developing follicles. However, when androgen exposure was gradually increased, we first observed suppression of oocyte development, followed by stagnation of follicle growth.
These data provide the rationale for androgen treatment in women with low ovarian reserve, but call for caution as over-replacement might cause harm to oocyte quality. Furthermore, this study describes mechanisms which might contribute to the follicular developmental arrest that is observed in androgen excess conditions such as polycystic ovary syndrome.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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