ESTROGEN BIOSYNTHESIS - REGULATION, ACTION, REMOTE EFFECTS, AND VALUEOF MONITORING IN OVARIAN STIMULATION CYCLES

Objective: To review current knowledge regarding estrogen biosynthesis , its regulation and action, specifically concerning local as opposed to remote effects of this hormone, and to examine the effectiveness an d prognostic value of monitoring hormone concentrations and endometria l response in cycles of controlled ovarian hyperstimulation. Data Iden tification and Selection: Studies that relate specifically to estrogen biosynthesis, enzymatic pathways, estrogen receptor physiology, and t he clinical aspects of estrogen monitoring were identified through lit erature and Medline searches. Results: Folliculogenesis is the basic u nit of ovarian activity, which has a dual purpose: oocyte maturation a nd steroid production. Steroidogenic granulosa and theca cells coopera te under gonadotropin control to produce estrogens by stimulating synt hesis of steroidogenic enzyme messenger RNAs. Steroid synthesis is amp lified further by local growth factors and follicular cell multiplicat ion. Estrogen synthesis is directed by FSH, and only small amounts of LH are needed to amplify the follicular estrogenic potential. However, the growth of preovulatory follicles can proceed without LH, under FS H regulation only, even in the presence of low peripheral estrogen lev els. Oocyte maturation and fertilization may proceed independently of ambient estrogen levels, leading to the assumption that estrogen exert s a minimal autocrine-paracrine function. The notable effect of follic ular estrogen production is to promote adequate receptive endometrium for embryo implantation. Clinical treatment cycles may be monitored mo re effectively by evaluating end-organ response to estrogen rather tha n by evaluating absolute serum E(2) concentrations or sonographic foll icular measurements. Conclusion: Follicular estrogen production is reg ulated by a complex set of signals that synergize to produce optimal s teroidogenesis. Most importantly, the effect of estrogen is truly an e ndocrine effect, as it prepares the endometrium for implantation. Ther efore, the goal of effective treatment and monitoring strategies shoul d focus on direct assessment of the biologic activity of estrogen as i t optimizes endometrial receptivity in anticipation of subsequent impl antation.