title: Characterization of the reproductive effects of the anorexigenic VGF-derived peptide TLQP-21: in vivo and in vitro studies in male rats.
abstract: VGF (nonacronymic) is a 68-kDa protein encoded by the homonymous gene, which is expressed abundantly at the hypothalamus and has been involved in the control of metabolism and body weight homeostasis. Different active peptide fragments are generated from VGF, including TLQP-21. Circumstantial evidence has suggested that VGF might also participate in the control of reproduction. Yet its mechanisms of action and the eventual role of specific VGF-derived peptides on the hypothalamic-pituitary-gonadal (HPG) axis remain unknown. Herein we report a series of studies on the reproductive effects of TLQP-21 as evaluated in male rats by a combination of in vivo and in vitro analyses. Central administration of TLQP-21 induced acute gonadotropin responses in pubertal and adult male rats, likely via stimulation of GnRH secretion, as documented by static incubations of hypothalamic tissue. In addition, in pubertal (but not adult) males, TLQP-21 stimulated LH secretion directly at the pituitary level. Repeated central administration of TLQP-21 to pubertal males subjected to chronic undernutrition was able to ameliorate the hypogonadotropic state induced by food deprivation. In contrast, chronic administration of TLQP-21 to fed males at puberty resulted in partial desensitization and puberty delay. Finally, in adult (but not pubertal) males, TLQP-21 enhanced hCG-stimulated testosterone secretion by testicular tissue in vitro. In summary, our data are the first to document a complex and multifaceted mode of action of TLQP-21 at different levels of the male HPG axis with predominant stimulatory effects, thus providing a tenable basis for the (direct) reproductive role of this VGF-derived peptide.
authors.affiliation: Physiology Section, Dept. of Cell Biology, Physiology, and Immunology, Faculty of Medicine, Univ. of Córdoba, Avda. Menéndez Pidal s/n, Córdoba, Spain. fi1agbee@uco.es
authors.forename: Leonor
authors.initials: L
authors.lastname: Pinilla
authors.forename: Rafael
authors.initials: R
authors.lastname: Pineda
authors.forename: Francisco
authors.initials: F
authors.lastname: Gaytán
authors.forename: Magdalena
authors.initials: M
authors.lastname: Romero
authors.forename: David
authors.initials: D
authors.lastname: García-Galiano
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sánchez-Garrido
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Pino
authors.forename: Manuel
authors.initials: M
authors.lastname: Tena-Sempere
authors.forename: Enrique
authors.initials: E
authors.lastname: Aguilar
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D031204:Caloric Restriction; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009479:Neuropeptides / Q000096:biosynthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D001067:Appetite Depressants; D006062:Gonadotropins; D009479:Neuropeptides; D010446:Peptide Fragments; C522412:TLQP-21 peptide; C062040:Vgf protein, rat; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone