Deciphering The Role Of Kisspeptin In The Mediation Of Photoperiod and Gonadal Steroid Signalling Throughout Reproduction

University Of Maryland Baltimore County, Baltimore MD

Investigators

Abstract

Kisspeptin is emerging as an important regulator of reproduction in vertebrates. In mammals, it is considered to be the "missing link" that mediates environmental and endogenous information to the hypothalamic-pituitary-gonadal (HPG) axis via integration of sensory input and transmission to gonadotropin-releasing hormone (GnRH) neurons. Accumulating evidence suggests that the kisspeptin system acts similarly in teleosts, which comprise the largest class of vertebrates. However, the study of teleost kisspeptin lags significantly behind that of mammals. Unlike mammals that possess only single forms of kisspeptin (KiSS1) and its receptor (KiSS1R), two isoforms of kisspeptin (Kiss1 and Kiss2) and two receptors (Kiss1r and Kiss2r) are expressed in the brain of most teleost species. Each receptor is activated by the two kisspeptin forms but shows preference to one form of kisspeptin. Preliminary data in striped bass suggests that the two kisspeptins have differential roles in the control of reproduction. Moreover, kiss1r- and kiss2r-expressing neurons interact in different ways with GnRH neurons in the hypothalamic preoptic area. To elucidate the exact roles of each form, the kisspeptins and cognate receptors of the striped bass will be used to pursue specific, selective, and efficient antagonists for the teleost kisspeptin receptors. As a first step, a suite of systematically modified kisspeptin peptides will be screened in vitro for their ability to block kiss1r and kiss2r stably expressed in a COS7 cell line, via two signal transduction pathways, PKC and PKA. The selected candidates will then be evaluated in vivo for their biological potencies, efficiency and specificity in short term and long term treatments. In the short-term experiments, kiss1 or kiss2 will be co-injected with the tested antagonist into striped bass. Controlled release delivery implants will be utilized in the long term experiments. These devices will be pre-implanted two weeks prior to kiss1 or kiss2 injections. The ability to block kiss1 and kiss2 will be determined by comparison to known kiss1/kiss2 effects on key hormones within the reproductive system (GnRHs, LH and FSH). The study is expected to yield at least one potent specific antagonist for each kisspeptin receptor, thereby enabling studies on the exact roles and significance of each of the two kisspeptin systems in the mediation of different signals in various brain pathways, particularly those affecting the reproductive axis. This tool will pave the way for a wider range of studies in the field of reproductive endocrinology in vertebrates. The potential impacts include improvement of reproductive manipulations of farmed and captive animals.