Reproduction Abstracts

GnRH neurons represent the primary neuroendocrine link between the brain and the rest of the reproductive system, and traditionally it has been assumed that a single population of GnRH neurons controls both pusatile LH release as well as the preovulatory LH surge. This view has profoundly influenced our strategies for contraception and for the treatment of infertility in women. Recent data from our laboratory, however, questions the validity of this fundamental assumption. Using the female rhesus monkey as a translational animal model, we found that: i) primates express two distinct molecular forms of GnRH, both of which are highly effective at stimulating LH release; ii) GnRH-I and GnRH-II, are encoded on different chromosomes, and the neurons that secrete them have completely distinct locations in the hypothalamus; and iii) GnRH-I neurons respond to oestrogen exclusively in a negative manner, while GnRH-II neurons respond to oestrogen exclusively in a positive manner. Taken together, these data suggest that different aspects of reproductive function in primates are orchestrated by two distinct populations of GnRH neurons, with GnRH-II neurons playing the primary role in mediating the oestrogen-induced preovulatory LH surge. Moreover, these findings suggest that it may be possible to selectively silence this subpopulation of neurons in humans, using pharmacological agents – thereby blocking ovulation while leaving the rest of the reproductive axis relatively unperturbed.