Oscillations of estradiol and gonadotropins are a missing link to solving the mystery of mono-ovulation in humans
VOLUME 116, ISSUE 3, P630-632
Dmitri I. Dozortsev, M.D., Ph.D., Antonio Pellicer, M.D., Michael P. Diamond, M.D.
Regulation of follicular development leading to mono-ovulation remains one of the unsolved mysteries of human reproduction. The current working hypothesis in part postulates that as multiple follicles grow, they produce estradiol, which exerts continued negative feedback on the follicle-stimulating hormone (FSH) synthesis. As the availability of FSH declines to a threshold sufficient to sustain the development of only a single follicle (with the higher number of FSH receptors), it becomes dominant, destined to be the only one that will eventually ovulate. Other factors, including Inhibin B and the pulsatile nature of FSH, also may have a role, as may local factors, such as bone morphogenetic protein 15 and some other peptides, in follicular competition in primates. However, in humans, there is compelling evidence that the mono-ovulation conundrum must be explained at the systemic level. Indirect evidence for systemic influence stems from the observation that when negative feedback on FSH is blocked with a low dose of clomiphene citrate, a woman with two ovaries develops the same number of follicles as a woman with one ovary (Diamond et al. ). The concept of a systemic level of regulation subsequently has been strengthened by the direct demonstration that the ovulation side in women is random, and is not influenced by prior ovulation, or any other local factors (Ecochard and Gougeon ).