title: Thyrotropin-releasing hormone decreases leptin and mediates the leptin-induced pressor effect.
abstract: Leptin, an adipocyte-released hormone, modifies food intake and energy expenditure regulating hypothalamic-pituitary-thyroid axis function. We previously reported that thyrotropin-releasing hormone (TRH) precursor gene overexpression induces hypertension in the normal rat and that spontaneously hypertensive rats have central TRH hyperactivity with increased TRH synthesis and release and an elevated TRH receptor number. In both models, intracerebroventricular antisense (AS) treatment against the TRH precursor produced a dose-dependent reduction of the increased diencephalic TRH content while normalizing high arterial blood pressure. In this article, we report that male Wistar rats that were made hypertensive by intracerebroventricular injection of a eucaryotic expression plasmid containing the pre-TRH cDNA showed decreased leptin plasma levels and that pre-TRH AS treatment reversed this phenomenon. In addition, male and female spontaneously hypertensive rats showed lower levels of circulating leptin than did sex-matched Wistar-Kyoto control rats. This difference also was abated by the pre-TRH AS treatment. Conversely, 20 microg ICV leptin induced a long-lasting pressor effect (18 +/- 5 mm Hg, n=6, P<0.01, >60 minutes) that was not observed in pre-TRH AS pretreated rats (2 +/- 3 mm Hg, n=6) but persisted in rats used as controls that were treated with inverted oligonucleotide (20 +/- 6 mm Hg, n=4, P<0.01). These data suggest that in rats with TRH-induced hypertension, leptin is decreased, inducing compensatory adiposity. We propose that because leptin produces central TRH synthesis and release, obesity may induce hypertension through TRH system activation and that the TRH-leptin interaction may thus contribute to the strong association between hypertension and obesity.
authors.affiliation: Cardiología Molecular, Instituto de Investigaciones Médicas A. Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Silvia I
authors.initials: SI
authors.lastname: García
authors.forename: María S
authors.initials: MS
authors.lastname: Landa
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Porto
authors.forename: Azucena L
authors.initials: AL
authors.lastname: Alvarez
authors.forename: Mariano
authors.initials: M
authors.lastname: Schuman
authors.forename: Samuel
authors.initials: S
authors.lastname: Finkielman
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Pirola
mesh_terms: D000818:Animals; D005260:Female; D020738:Leptin / Q000378:metabolism*; D008297:Male; D011311:Pressoreceptors / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
chemical_list: D020738:Leptin; D013973:Thyrotropin-Releasing Hormone