Basic Sciences of Medicine 2014, 3(4): 63-68 DOI: 10.5923/j.medicine.20140304.01 Serum Kisspeptin Level in Experimentally Induced Hypogonadism Model of Adult Female Rats and Its Effect on Fertility Rania R. A. Atia * , Khaled A. A. Abulfadle Physiology department, Faculty of Medicine, Zagazig University, Egypt Abstract Objective: To investigate the effect of experimentally induced hypogonadism model of adult female rats on serum kisspeptin level and its effect on fertility. Experimental design: Total number of 18 healthy, adult, female albino rats were used. Rats were divided into three groups 6 rats each. Group I (control). Group II (ovariectomized, OVX). Group III (OVX estrogen-treated)were bilaterally ovariectomized adult female rats with recovery for 21 days then, three s.c. daily injections with estradiol (E 2 ) penzoate (2.5 µg/kg body weight) dissolved in sesame oil for three days. In all the three groups, kisspeptin level and estradiol levels were estimated at the proper time for each group. Results: This study revealed that there is a significant decrease in serum levels of both estradiol (14.12±0.86) and kisspeptin (1.03±0.16) in ovariectomized (OVX) group in comparison to those in the control group (27.47±2.38) and (2.11±0.31) respectively. But, there is an insignificant decrease in serum levels of both estradiol (25.39±1.96) and kisspeptin (1.87±0.27) in OVX estrogen-treated group in comparison to those in the control group (27.47±2.38) and (2.11±0.31) respectively. Conclusions: There is a link between serum levels of kisspeptin and estradiol which confirmed that sex steroids play a major role in serum kisspeptin level regulation which in turn affects fertility. To our knowledge, this is the first study to estimate the effect of ovariectomy and estradiol replacement on serum levels of kisspeptin in experimental animal models. Keywords Kisspeptin, Estradiol, Fertility, Ovariectomy 1. Introduction Metastin, a metastasis suppressor gene encoding a 54-amino-acid peptide is known asKiSS-1. [1] KiSS-1 gene gives origin to kisspeptins by differential proteolytic processing of its product. [2] Actions of kisspeptins are conducted through G protein-coupled receptor 54(GPR54). [3] KiSS-1/GPR54 system has been involved in tumor progression and metastasis, and potent antimetastasis actions of KiSS-1 peptide have been described in papillary thyroid carcinoma, breast carcinoma, melanoma, and pancreatic cancer cells. [4] In addition, it was recently proposed that KiSS-1 peptides likely play a role in the physiological regulation of trophoblast invasion [5] and initial evidence suggested that KiSS-1 may participate in the regulation of specific neuroendocrine systems asthe release of oxytocin. [2] Indeed, the expression of KiSS-1/GPR54 system has been found in placenta, different brain areas as hypothalamus, spinal cord, pituitary, pancreas, and human plasma [6], which strongly suggests additional physiological functions * Corresponding author: raniareafaat777@gmail.com (Rania R. A. Atia) Published online at http://journal.sapub.org/medicine Copyright © 2014 Scientific & Academic Publishing. All Rights Reserved of this newly discovered system. Recently, it was found that there is a role for KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion, brain sex differentiation, puberty onset and fertility [7]. In addition, studies on rodents and sheep suggested that hypothalamic expression of Kiss1 and/or kisspeptin fiber distribution are altered after inappropriate exposures to synthetic estrogenic compounds during development. [8] On the other hand, mice and humans lacking kisspeptin receptor expression showed a phenotype of hypogonadotrophic hypogonadism and consequent infertility. [9] Moreover, Kiss1 system has been recently recognized as a regulator of the reproductive axis, which is indispensable for its timely activation at puberty and its proper function including fertility during adult life. [10] The primary mechanism whereby kisspeptins participate in the control of the reproductive axis involves its ability to operate upon, and stimulate, GnRH neurons, which have been shown to express GPR54. [11]. It was found that blocking of kisspeptin actions causes elimination of the pre-ovulatory peak of gonadotropins in cyclic female rats. [12] Also, kisspeptins play an essential role in regulation of timing of puberty, as evidenced by a combination of genetic, physiologic and pharmacological analyses in rodents and primates. [13] The hypothalamic Kiss1 system undergoes a complex activation program during puberty, which involves