Presence of kiss1/kiss1r system at the pituitary, testis and adipose tissue in rodents: functional actions and regulation by physiological cues
Ester Gutierrez-Pascual, Jose Córdoba-Chacon, Leonor Pinilla, Francisco Gracia-Navarro, Raul M Luque, María M Malagón, Manuel Tena-Sempere, Antonio J Martínez-Fuentes & Justo P Castaño
It is now widely accepted that the kisspeptins (kps) and their receptor kiss1r play an essential role in the neuroendocrine regulation of the reproductive axis by stimulating hypothalamic GnRH secretion. However, kiss1 and kiss1r expression in tissues distinct from, but related to, the hypothalamus, prompted us to propose that these molecules may exert regulatory functions in additional places of the neuroendocrine system, such as the pituitary and two of its physiological targets: testis and adipose tissue. We have previously demonstrate that the kiss1/kiss1r system is functionally expressed in pituitary cells from peripubertal rats, where kp-10 directly acts on a subset of both gonadotropes and somatotropes by increasing [Ca2+]i and, consequently, stimulating LH and GH release, respectively. Moreover, we have observed that estradiol differentially facilitates kp-10 action at the pituitary level, by sensitizing, especially in somatotropes, the response to this peptide. To clarify the function of kiss1/kiss1r system at these different levels, we have analyzed the regulation of its expression by physiologically relevant factors and conditions. This revealed that the kiss1/kiss1r system is under a fine, age- and gender-dependent regulation in pituitary, where their expression levels undergo dramatic changes throughout postnatal development, as well as after in vitro treatment with GnRH, GHRH and/or kp-10, and under different metabolic conditions. Additionally, we observed that the kiss1/kiss1r system is expressed in peripheral tissues, such as testis and adipose tissue, and that this expression is differentially regulated during postnatal development, as well as by metabolic factors and energy status. Taken as a whole, our results suggests that the kiss1/kiss1r system exerts additional neuroendocrine functions, distinct from the hypothalamic control of reproductive axis, and support the hypothesis that this system may operate as an integrator between metabolic, somatotropic and reproductive axes, by acting at multiple levels, from the hypothalamus to the pituitary and their peripheral target tissues.
BIO-0139, CTS-01705, BFU2007-60180/BFI, BFU2008-01136/BFI