Molecular mechanisms regulating follicular recruitment and selection

Ovarian follicular growth and development is an integrated process encompas sing both extraovarian signals, such as gonadotrophins and metabolic hormon es, and intraovarian factors. Follicular development has been classified in to gonadotrophin-independent and -dependent phases. In the latter, FSH prov ides the primary drive for follicular recruitment and LH is required for co ntinued development of follicles to the preovulatory stage. A transient inc rease in circulating FSH precedes the recruitment of a group of follicles, and these recruited follicles are characterized by expression of mRNAs enco ding P450scc and P450arom in granulosal cells. As follicles mature, there i s a transfer of dependency from FSH to LH, which may be part of the mechani sm(s) involved in selection of follicles for continued growth. Indeed, chan ges in the pattern of expression of mRNA for gonadotrophin receptors and st eroid enzymes within follicular cells appear to be closely linked to change s in peripheral concentrations of gonadotrophins. The mechanism of selectio n of dominant follicles still requires clarification, but seems to be linke d to the timing of mRNA expression encoding LHr and 3 beta-hydroxysteroid d ehydrogenase (3 beta HSD) in granulosal cells. Additional intraovarian syst ems, including the ovarian IGF and activin/inhibin systems, also exert a ro le. For example, it appears that the development of follicular dominance in cows is associated with the FSH-dependent inhibition of the expression of mRNA encoding insulin-like growth factor binding protein 2 (IGFBP-2) in gra nulosal cells. In conclusion, the integration of these endocrine signals an d intraovarian factors within follicles determines whether follicles contin ue to develop and become dominant or are diverted into apoptotic pathways l eading to atresia.