FOLLICULAR ESTROGEN SYNTHESIS - THE 2-CELL, 2-GONADOTROPIN MODEL REVISITED

The original 'two-cell mechanism' explained the endocrine regulation o f follicular oestrogen synthesis and implied paracrine signalling in t he follicle wall. It is now known that the CYP17 gene encoding 17-hydr oxylase/C-17-20-lyase activity crucial to androgen synthesis, is expre ssed exclusively in thecal cells. 17-Hydroxylase/C-17-20-lyase activit y is regulated by LH and subject to local modulation by a factor(s) em anating in FSH-stimulated granulosa cells. The FSH receptor gene is ex pressed exclusively in granulosa cells, where FSH acts directly to ind uce cytoproliferation and differentiation via cyclic AMP/protein kinas e-A mediated post-receptor signalling. Granulosa cells also express an drogen receptors, and theca-derived androgen has the potential to modu late locally differentiative responses to FSH. When follicles are recr uited to preovulatory development by FSH, their granulosa cells develo p LH receptors functionally coupled to aromatase activity and inhibin production. Thereby they simultaneously undertake LH-responsive aromat ization and inhibin synthesis. Inhibin has the potential to potently e nhance LH-stimulated thecal androgen synthesis. Granulosa-derived inhi bin may therefore participate in a paracrine mechanism that locally am plifies androgen synthesis, and hence oestrogen formation, in the preo vulatory follicle(s).