Endocrine and Local Control of the Primate Corpus Luteum: 1973 to Today.Richard L. Stouffer, Ph.D.

Abstract

Over 25 years have passed since the annual meeting of the Society for the Study of Reproduction included a session on the comparative aspects and advances in our knowledge of the corpus luteum (CL) in rodent, domestic animal and primate species. Using Dr. E. Knobil's 1973 perspective on the nonhuman and human CL as a starting point, key advances particularly over the past decade will be summarized. In addition, the influence of G. Niswender's research, as related to the elucidation of luteal cell types and the differences between luteinizing hormone (LH) and chorionic gonadotropin (CG)-receptor binding and signaling, will be examined. Finally, recurrent questions and opportunities for further research will be highlighted. Collectively, studies employing pulsatile gonadotropin releasing hormone (GnRH) or GnRH antagonist treatment reinforce the concept that pituitary LH is the primary luteotropic hormone in female monkeys and women, but can we rule out a role for other hormones, including prolactin-like factors? And do local effects of GnRH/GnRH antagonist in the CL complicate our interpretation of the results of LH ablation/replacement protocols? With the advent of monkey and human gene arrays, the transcriptome offers insight into LH-regulated genes (both up- and down-regulated) in the CL, but which are directly regulated by LH versus indirectly via LH-modulated local factors, including steroid hormones and growth factors? Our knowledge of the processes controlling CL development, particularly angiogenesis, has increased, but events leading to CL regression near the end of the nonfertile menstrual cycle remain a mystery. Since the life span of the CL during the menstrual cycle is not regulated by a uterine luteolytic factor, Knobil hypothesized that intraluteal "self-desruct" agents are responsible for luteal regression in primates. Are Knobil's candidates, estradiol and prostaglandin F 2alpha, or other agents, the likely factor(s)? What are the roles of theca-derived and granulosa-derived luteal cells, and luteal cell - nonluteal (microvascular; immune) cell interactions in controlling the functional lifespan of the primate CL? Also, what are the qualities of placental, LH-like CG that rescue the CL and extend its function into early gestation? Opportunities remain for innovative research at the systems, cellular and molecular levels to increase our understanding of primate CL structure-function that is relevant to fertility control and women's health. Supported by NIH NICHD R01HD20869, SCCPIR U54HD18185, CDRC U54HD55744; NCRR P51 RR00163; Schering AG.