Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Aug;97(8):E1458-67.
doi: 10.1210/jc.2012-1282. Epub 2012 May 10.

Kisspeptin administration to women: a window into endogenous kisspeptin secretion and GnRH responsiveness across the menstrual cycle

Yee-Ming Chan  1 , James P Butler, Valerie F Sidhoum, Nancy E Pinnell, Stephanie B Seminara
Affiliations

Kisspeptin administration to women: a window into endogenous kisspeptin secretion and GnRH responsiveness across the menstrual cycle

Yee-Ming Chan et al. J Clin Endocrinol Metab. 2012 Aug.

Abstract

Context: Kisspeptin is the most powerful known stimulus of GnRH-induced LH secretion across mammalian species. However, the effects of kisspeptin are just being explored, and the dynamics of kisspeptin responsiveness across the menstrual cycle are incompletely understood.

Objective: The objective of the study was to characterize the effects of kisspeptin on GnRH secretion in healthy women in different phases of the menstrual cycle.

Participants and intervention: Ten women in the early follicular phase, three women in the late follicular (preovulatory) phase, and 14 women in the midluteal phase received a bolus of kisspeptin 112-121 0.24 nmol/kg iv. An additional four women in the early to midfollicular phase received kisspeptin 112-121 0.72 nmol/kg iv.

Results: The response to kisspeptin varied depending on the phase of the menstrual cycle. LH pulses were observed immediately after kisspeptin administration in all luteal and preovulatory women. However, only half the women in the early follicular phase had unambiguous kisspeptin responses. Increasing the kisspeptin dose did not increase the LH response in early to midfollicular phase women. Kisspeptin did not appear to reset the GnRH pulse generator in women as it does in men.

Conclusions: Differences in responses to exogenous kisspeptin across the menstrual cycle suggest that kisspeptin tone is higher in the early follicular phase compared with other cycle phases. The mechanisms that determine the timing of GnRH pulse generation in men and women appear to be distinct.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Effects of kisspeptin on LH secretion. Representative patterns of LH secretion from two women each in the follicular (A and B), preovulatory (D and E), and luteal phases (G and H) of the menstrual cycle. Mean ± sem serum LH for all women in the early follicular (C), preovulatory (F), and luteal phases (I), aligned to the time of kisspeptin administration. Note the different y-axis in panels D–F. Arrows indicate time of kisspeptin administration; arrowheads indicate peaks of pulses.
Fig. 2.
Fig. 2.
Characteristics of LH pulses. A, Amplitude. B, AUC. C, Time from nadir to peak. NS, Not significant; Pre, before kisspeptin administration; Post, after kisspeptin administration.
Fig. 3.
Fig. 3.
Effects of kisspeptin on hormone concentrations. FSH (A) and estradiol (B) were measured in 2-h study pools.
Fig. 4.
Fig. 4.
Effects of kisspeptin on pulse intervals. A, Schematic of the predicted result if kisspeptin were to have no effect on the timing of endogenous pulses. Note that this is an idealized schematic and that actual pulse profiles show more variability in pulse intervals. A, Interval between endogenous pulses before kisspeptin; B, interval between the endogenous pulses immediately preceding and following the kisspeptin-induced pulse; B1, interval between the kisspeptin-induced pulse and the immediately preceding endogenous pulse; B2, interval between the kisspeptin-induced pulse and the immediately following endogenous pulse; C, interval between endogenous pulses after kisspeptin. B, Observed pulse intervals. Bars, Means. NS, Not significant.
See this image and copyright information in PMC

References

    1. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. 2003. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA 100:10972–10976 - PMC - PubMed
    1. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O'Rahilly S, Carlton MB, Crowley WF, Jr, Aparicio SA, Colledge WH. 2003. The GPR54 gene as a regulator of puberty. N Engl J Med 349:1614–1627 - PubMed
    1. Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF, Seminara S, Clifton DK, Steiner RA. 2004. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145:4073–4077 - PubMed
    1. 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. 2005. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA 102:1761–1766 - PMC - PubMed
    1. Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA, Bloom SR. 2005. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 90:6609–6615 - PubMed

Publication types