Gonadotropin-Releasing Response to Kisspeptin-10 and Its Modulation by Progesterone in Postpartum Cyclic Cows

Document Type : Research Article


1 Department of Theriogenology, Faculty of Agriculture, Iwate University, 0208550, Morioka, Japan Department of Animal Science, Faculty of Veterinary Medicine, South Valley University, 83523, Qena, Egypt

2 Department of Theriogenology, Faculty of Agriculture, Iwate University, 0208550, Morioka, Japan


The present study aimed to evaluate the effect of kisspeptin-10 (Kp10), a shorter variant of kisspeptin retaining full biological activity, on the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in cyclic adult cows, and the effect of plasma progesterone (P4)concentration on the response to Kp10 administration. The experiments were performed using five postpartum cows (4-5 years old) treated with a progesterone-releasing intravaginal device (PRID) for 7 days. The animals received a single intravenous (i.v.) injection of Kp10 (5 μg/kg b.w.: 3.85 nmol/kg b.w.) for three consecutive days after the device’s removal. Plasma concentrations of P4 were higher on the day of the PRID’s removal (day 0: 7.3±1.1 ng/mL) than 1 (day 1: 0.8±0.1 ng/mL) and 2 (day 2: 0.6±0.1 ng/mL) days later (P<0.05). Kp10 did not alter plasma LH concentrations significantly at day 0. However, it significantly stimulated the release of LH on day 1 and day 2 (P<0.05). Kp10 tended to stimulate the release of FSH at day 2; however, it did not alter the concentrations of FSH in plasma significantly throughout the experiment. The results showed that Kp10 stimulates the release of LH in postpartum cyclic cows, and suggested that high concentrations of P4 inplasma may reduce the effect of kisspeptin on the secretion of gonadotropins.


Baulieu E.E. (1998). Neurosteroids: a novel function of the brain. Psychoneuroendocrine. 23, 963-987.
Calogero A.E., Palumbo M.A., Bosboom A.M.J., Burrello N., Ferrara E., Palumbo G., Petraglia F. and D'Agata R. (1998). The neuroactive steroid allopregnanolone suppresses hypothalamic gonadotropin releasing hormone release through a mechanism mediated by γ-aminobutyric acid a receptor. J. Endocrinol. 158, 121-125.
Ezzat A.A., Saito H., Sawada T., Yaegashi T., Yamashita T., Hirata T.I., Sawai K. and Hashizume T. (2009). Characteristics of the stimulatory effect of Kisspeptin-10 on the secretion of luteinizing hormone, follicle-stimulating hormone and growth hormone in prepubertal male and female cattle. J. Reprod. Dev. 55, 650-654.
Fox S., Harlan R.E., Shivers B. and Pfaff D.W. (1990). Chemical characterization of neuroendocrine targets for progesterone in the female rat brain and pituitary. Neuroendocrinology. 51, 276-283.
Genazzani A.R., Palumbo M.A., De Micherouz A.A., Artini P.G., Criscuolo M., Ficarra G., Guo A., Benelli A., Bertolini A., Petraglia F. and Purdy R.H. (1995). Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats. Eur. J. Endocrinol. 133, 375-380.
Gottsch M.L, Clifton D.K. and Steiner R.A. (2009). From KISS1 to kisspeptins: an historical perspective and suggested nomenclature. Peptides. 30, 4-9.
Gottsch M.L., Cunningham M.J., Smith J.T., Popa S.M., Acohido B.V., Crowley W.F., Seminara S., Clifton D.K. and Steiner R.A. (2004). A role of kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 145, 4073-4077.
Hashizume T., Saito H., Sawada T., Yaegashi T., Ezzat A.A., Sawai K. and Yamashita T. (2010). Characteristics of stimulation of gonadotropin secretion bykisspeptin-10 in female goats. Anim. Reprod. Sci. 118, 37-41.
Hashizume T., Takahashi Y., Numata M., Sasaki K., Ueno K., Ohtsuki K., Kawai M. and Ishi A. (1999). Plasma profiles of growth hormone, prolactin and insulin-like growth factor-I during gestation, lactation and neonatal period in goats. J. Reprod. Dev. 45, 273-281.
Irwig M.S., Fraley G.S., Smith J.T., Acohido B.V., Popa S.M., Cunningham M.J., Gottsch M.L., Clifton D.K. and Steiner R.A. (2004). Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology. 80, 264-272.
Kadokawa H., Matsui M., Hayashi K., Matsunaga N., Kawashima C., Shimizu T., Kida K. and Miyamoto A. (2008). Peripheral administration of kisspeptin-10 increases plasma concentrations of GH as well as LH in prepubertal Holstein heifers. J. Endocrinol. 196, 331-334.
Kile J.P. and Nett T.M. (1994). Differential secretion of follicle-stimulating hormone and luteinizing hormone from ovine pituitary cells following activation of protein kinase A, protein kinase C, or increased intracellular calcium. Biol. Reprod. 50, 49-54.
Lents C.A., Heidorn N.I., Barb C.R. and Ford j.j. (2008). Central and peripheral administration of kisspeptin activates gonadotropin but not somatotropin secretion in prepubertal gilts. Reproduction. 135, 879-887.
Lesoon L.A. and Mahesh V.B. (1992). Stimulatory and inhibitory effects of progesterone on FSH secretion by the anterior pituitary. J. Steroid Biochem. Mol. Biol. 42, 479-491.
Mahesh V.B. and Brann D.W. (1998). Regulation of the preovulatory gonadotropin surge by endogenous steroids. Steroids. 63, 616-629.
Mensah Nyagan A.G., Do Rego J.L., Beaujean D., Luu The V., Pelletier G. and Vaudry H. (1999). Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system. Pharmacol. Rev. 51, 63-81.
Navarro V.M., Castellano J.M., Fernandez-Fernandez R., Tovar S., Roa J., Mayen A., Barreiro M.L., Casanueva F.F., Aguilar E., Dieguez C., Pinilla L. and Tena-Sempere M. (2005). Effects of kiss-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat. Endocrinology. 146, 1689-1697.
O'Byrne K.T., Thalabard J.C., Grosser P.M., Wilson R.C., Williams C.L., Chen M.D., Ladendorf D., Hotchkiss J. and Knobil E. (1991). Radiotelemetric monitoring of hypothalamic gonadotropin-releasing hormone pulse generator activity throughout the menstrual cycle of the rhesus monkey. Endocrinology. 129, 1207-1214.
Phillips D.J. (2005). Activins, inhibins, and follistatins in the large domestic species. Domest. Anim. Endocrinol. 28,1-16.
Prakash B.S., Meyer H.H.D., Schallenberger E. and Van De Wiell D.F.M. (1987). Development of a sensitive enzyme immunoassay (EIA) for progesterone determination in unextracted bovine plasma using the second antibody technique. J. Steroid Biochem. 28, 623-627.
Robertson D.M., Hale G.E., Jolley D., Fraser I.S., Hughes C.L. and Burger H.G. (2009). Interrelationships between ovarian and pituitary hormones in ovulatory menstrual cycles across reproductive age. J. Clin. Endocrinol. Metab. 94, 138-144.
Sim J.A., Skynner M.J. and Herbison A.E. (2001). Direct regulation of postnatal GnRH neurons by the progesterone derivative allopregnanolone in the mouse. Endocrinology. 142, 4448-4453.
Skinner D.C., Evans N.P., Delaleu B., Goodman R.L., Bouchard P. and Caraty A. (1998). The negative feedback actions of progesterone on gonadotropin releasing hormone secretion are transduced by the classical progesterone receptor. Proc. Natl. Acad. Sci. USA. 95, 10978-10983.
Sleiter N., Pang Y., Park C., Horton T.H., Dong J., Thomas P. and Levine J.E. (2009). Progesterone receptor A (PRA) and PRB-independent effects of progesterone on gonadotropin-releasing hormone release. Endocrinology. 150, 3833-3844.
Stevenson J.S. (2008). Progesterone, follicular, and estrual responses to progesterone-based estrus and ovulation synchronization protocols at five stages of the estrous cycle. J. Dairy Sci. 91, 4640-4650.
Ueblinger H., Binder H., Hauser B., Rüsch P. and Zerobin K. (1995). Hormonanalytischer vergleich der vaginaleinlagen CIDRTM und PRID bei ovariektomierten kühen. Schweiz. Arch. Tierheilk. 137, 81-86.
Whitlock B.K., Daniel J.A., Wilborn R.R., Rodning S.P., Maxwell H.S., Steele B.P. and Sartin J.L. (2008). Interaction of estrogen and progesterone on kisspeptin-10-stimulated luteinizing hormone and growth hormone in ovariectomized cows. Neuroendocrinology. 88, 212-215.