Okay everyone, I'm ready to get this puppy off the ground! Official discussion of this paper will begin Sat. Jan 28. Until then, here is the link to the full article, the citation, and a bit of introduction to the topic. Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, Thresher RR, Malinge I, Lomet D, Carlton MB, Colledge WH, Caraty A, Aparicio SA. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1761-6. http://www.pnas.org/cgi/content/full/102/5/1761 Note: you can also download a PDF version from the site I've linked to if you prefer that format for reading. By way of introduction to the topic, as many of you may be aware, my field of research is in reproductive neuroendocrinology...yes, it's a mouthful, and basically means I study how the brain controls the production and release of hormones involved in reproductive function. Over the past year or two, a recently discovered protein, known as kisspeptin, has become a hot topic in the field. As the article you will read indicates, the current hypothesis is that kisspeptin, acting through its receptor, GPCR 54, is required for the release of gonadotropin-releasing hormone (GnRH) from terminals of neurons that are located in a structure at the base of the part of the hypothalamus, called the median eminence, and into the blood vessels that carry neuroendocrine hormones to the anterior pituitary (pituitary portal vessels). A few things that should be noted with regard to this system, which I hope will help you understand what you're reading better: Anatomy - GnRH neuronal perikarya (cell bodies) are scattered throughout the hypothalamus, which makes them more challenging to study than neurons located in restricted nuclei of the brain, because you cannot easily target the cell bodies with drugs, or to even lesion them. The axons, however, converge so that the terminals of these neurons are mainly located in the median eminence. Some scattered terminals are present in areas contacting the brain ventricles and more caudally (toward the tail), in parts of the brain involved in reproductive behavior, but we don't know if these terminals are important for reproductive behavior (yet). Pattern of release - GnRH, during most of the estrous/menstrual cycle in females, and under normal physiological conditions in males, is released in a pulsatile pattern. The frequency at which these pulses are released is dependent on the concentrations of progesterone (more progesterone, slower pulses) in females, and testosterone in males, and the amplitude of these pulses is dependent on the concentrations of estradiol (more estradiol, lower amplitude) in both sexes. This is part of the normal, negative feedback control of the hypothalamo-pituitary-gonadal axis, where increased steroid hormones produced by the gonads regulate the secretory patterns of GnRH. GnRH in turn regulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary into peripheral blood circulation, which reaches the gonads. The pattern of LH and FSH secretion alters the rate of secretion of progesterone, estradiol and testosterone from the gonads, etc. Prior to ovulation, the pattern of secretion of these hormones changes dramatically, and the mechanism remains elusive. Rather than pulses of GnRH and LH being the predominant pattern of release, and negative feedback of estradiol on GnRH and LH being the predominant feedback mechanism, there is a shift to what we call a positive feedback loop, where increasing concentrations of estradiol result in increasing release of GnRH, which increases LH, until we observe a sustained release of very high concentrations of GnRH known as the GnRH surge. During this time, there may still be underlying pulse release, but pulses are not detectable. Okay, I think that's a bit of a start, and will give everyone something to chew on as they delve into the article.