Neuroendocrine effects of progesterone

Progesterone (P) is secreted by the corpus luteum under the control of gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH). Progesterone (P) is essential for reproduction because: (1) it induces in the endometrium the transcription of specific genes involved in the implantation of the blastocyst, (2) it modulates GnRH/LH secretion by decreasing GnRH pulse frequency, which in turn enriches the gonadotroph cells in FSH and avoids a second LH surge. Using the ewe as a model, we investigated the immediate GnRH and LH responses to acute changes of circulating P levels. Our results show that P changes cause dramatic modifications in GnRH pulse frequency: P removal induces an acceleration of the pulse generator, while P administration slows the pulse frequency. LH secretion was modified in parallel to the changes in GnRH. Other experiments proved that these neuroendocrine effects of P are mediated by P itself, not by its hydroxylated metabolites, and occur at the level of P receptors. Finally, these effects require priming by estradiol. Additionally, in the final stage of the follicular phase, P plays a role in the triggering of the LH surge. This has been shown in rodents, non-human primates, and in women. Such a phenomenon is not observed in ewes, although in these species luteal P modulates the amplitude of the estradiol-induced LH surge.