Kisspeptin Stimulates Adrenocorticotrophic Hormone Release via Corticotrophin-Releasing Factor

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 72-87-HPA Axis
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-76
Shoko Shibata*1, Kosuke Yogo1, Kazunori Kageyama2, Kazumi Iino1, Toshihiro Ohishi1, Keisuke Kakizawa1, Yuta Ohkawa1 and Yutaka Oki1
1Hamamatsu Univ Sch of Med, Hamamatsu, Japan, 2The Third Dept of Internal Med, Hirosaki Aomori, Japan

Kisspeptin plays an important role in regulating the reproductive-axis. Recent studies have shown that kisspeptin neurons have many projections to non-reproductive areas of the brain including the paraventricular nucleus (PVN) of the hypothalamus. Nonetheless, little is known about the role of kisspeptin in the hypothalamic-pituitary-adrenal (HPA) axis. We investigated whether kisspeptin is involved in the regulation of the HPA axis.


In male Sprague-Dawley rats weighing 160–180 g, an indwelling jugular vein cannula was inserted and fixed, and s stainless-steel single guide cannula was implanted into the lateral cerebroventricle. Kssspeptin was administered intravenously or intracerebroventricularly. Blood samples were taken after the administration, and plasma ACTH and LH were measured by radioimmunoassay.


In conscious and unrestrained male rats, the intravenous administration of 20 nmol kisspeptin increased plasma LH but did not affect plasma ACTH levels. On the other hand, the intracerebroventricular (icv) administration of 3.0 and 5.0 nmol kisspeptin increased plasma ACTH levels in a dose-dependent manner at 15 min after stimulation (vehicle vs. 3.0 vs. 5.0 nmol kisspeptin: 51.2 ± 11.1 vs. 108.1 ± 23.4 vs. 197.0 ± 47.5 pg/ml, respectively). Pretreatment with astressin, a CRF receptor antagonist, inhibited the increase in plasma ACTH levels induced by icv administration of 5.0 nmol kisspeptin at 15 min (164.6 ± 21.4 vs. 57.7 ± 6.7 pg/ml,) and at 30 min (43.4 ± 8.6 vs. 76.1 ± 11.7 pg/ml). To elucidate the distribution of GPR54 gene expression, we used a homologous PVN neuronal cell line, 4B cells. Expression of GPR54 mRNA was detected by RT-PCR. In addistion, the expression of CRF mRNA in 4B cells was increased by kisspeptin.


In conclusion, we suggest that central kisspeptin activates the HPA axis through hypothalamic CRF.

Nothing to Disclose: SS, KY, KK, KI, TO, KK, YO, YO

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