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Effects of Polypeptide YY_3–36 upon Luteinizing Hormone-Releasing Hormone and Gonadotropin Secretion in Prepubertal Rats: In Vivo and in Vitro Studies

Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Córdoba, Spain

Address all correspondence and requests for reprints to: Leonor Pinilla, Physiology Section, Department of Cell Biology, Physiology, and Immunology, Faculty of Medicine, University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain. E-mail: fi1agbee{at}uco.es.

Polypeptide YY_3–36 (PYY_3–36) is a gastrointestinal secreted molecule, agonist of neuropeptide Y (NPY) receptor subtypes Y₂ and Y₅, recently involved in the control of food intake. Notably, several factors with key roles in energy homeostasis conduct pleiotropic effects upon the reproductive axis. However, whether PYY_3–36 is provided with similar biological actions remains so far largely unexplored. To address this issue, expression analyses of neuropeptide Y receptor Y₂ and Y₅ genes were conducted at the pituitary and the hypothalamus, and functional studies testing the effects of PYY_3–36 in vivo and in vitro were implemented, using the prepubertal rat as a model. Expression of the genes encoding Y₂ and Y₅ receptors was demonstrated, albeit at low levels, in whole hypothalamic and pituitary samples, and challenge of pituitary tissue with increasing doses of PYY_3–36 elicited LH and FSH secretion in male and female rats, a response that was persistently observed in the absence of extracellular calcium. Moreover, 10^–6 M PYY_3–36 enhanced LH and FSH responsiveness to LHRH in vitro. In contrast, systemic ip administration of PYY_3–36 over a range of doses (3, 10, and 30 µg/kg) failed to significantly modify serum LH levels in males and females, whereas central (intracerebroventricular) injection of 3 nmol PYY_3–36 inhibited LH secretion in vivo, and 10^–6 M PYY_3–36 decreased LHRH release by hypothalamic fragments in vitro in male but not in female rats. Overall, our data document the complex mode of action of the gut-derived anorexigenic signal PYY_3–36 at the hypothalamic-pituitary unit in the control of gonadotropin secretion and evidence that, as is the case for other peripheral factors with key roles in energy balance (as leptin and ghrelin), PYY_3–36 might play a role in the neuroendocrine modulation of the reproductive axis.

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