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Submitted on January 27, 2006
Accepted on June 23, 2006
Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Córdoba, Spain; Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain; and Instituto Valenciano de Infertilidad (A.P.), 46015 Valencia, Spain
* To whom correspondence should be addressed. E-mail: fi1tesem{at}uco.es.
Kisspeptins, the products of KiSS-1 gene, and their receptor, GPR54, have recently emerged as essential gatekeepers of reproduction, mainly through regulation of GnRH secretion at the hypothalamus. However, the profound hypogonadotropism linked to GPR54 inactivation is likely to mask additional functions of this system at other levels of the gonadal axis, where expression of KiSS-1 and GPR54 has been preliminary reported. We describe herein the expression of KiSS-1 gene and kisspeptin immunoreactivity (IR) in rat ovary, and evaluate its developmental and hormonal regulation. KiSS-1 and GPR54 mRNAs were persistently detected in adult ovary along estrous cycle. Yet, contrary to GPR54, ovarian KiSS-1 levels fluctuated in a cyclic-dependent manner, with a robust increase in the afternoon of proestrus, i.e. preceding ovulation. In addition, kisspeptin-IR was observed in rat ovary, with strong signals in theca layers of growing follicles, corpora lutea and interstitial gland; compartments where modest GPR54-IR was also detected. Interestingly, the rise in ovarian KiSS-1 mRNA at proestrus was prevented by blockade of pre-ovulatory gonadotropin surge and restored by replacement with hCG, as super-agonist of LH. In addition, immature ovaries showed low to negligible levels of KiSS-1 mRNA, which were significantly enhanced by gonadotropin priming. In summary, we present novel evidence for the developmental and hormonally regulated expression of KiSS-1 gene, and the presence of kisspeptin-IR, in rat ovary. The ability of the LH surge to timely induce ovarian expression of KiSS-1 at the pre-ovulatory period strongly suggests a previously unsuspected role of locally produced kisspeptin in the control of ovulation.
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