Systemic administration of leptin decreases plasma corticosterone levels: role of hypothalamic norepinephrine.
Leptin, an adipocyte-derived hormone, is known to regulate a variety of neuroendocrine functions. It inhibits the hypothalamo-pituitary-adrenal axis (HPA) in several animal models, however, the exact mechanism by which it does so is not known. Since norepinephrine (NE) is a key regulator of the HPA axis, we hypothesized that leptin could suppress HPA activity by decreasing NE levels. To study this, we implanted adult male Sprague-Dawley rats with both a push-pull cannula in the paraventricular nucleus (PVN) and a catheter in the jugular vein. Animals were treated with either 0 or 100 microg or 500 microg of recombinant rat leptin (Lep). Push-pull perfusion was performed from 1000-1600 h. Perfusate samples were collected every 30 min and analyzed for NE levels using HPLC-EC. Blood samples were collected every 60 min and analyzed for corticosterone (CS) levels. To further understand the role of NE in this phenomenon animals were treated with either an alpha1-adrenergic agonist, phenylephrine (PHE; 0.5 mg/kg BW), an alpha2-adrenergic agonist, clonidine (CLON; 0.6 mg/kg BW), or a beta-adrenergic agonist, isoproterenol (ISO; 0.2 mg/kg BW) alone or in combination with 500 microg of Lep. Pre-treatment and hourly post-treatment blood samples were collected, plasma was separated and analyzed for CS levels. Leptin administration decreased NE release in the PVN significantly by 30 min (p<0.05). It also significantly reduced plasma CS levels at 240 and 300 min (p<0.05). Administration of either PHE or CLON in combination with leptin prevented the leptin-induced decrease in CS. In contrast, administration of ISO along with leptin did not prevent the leptin-induced decrease in CS. These results indicate that leptin decreases hypothalamic NE and plasma CS and that this effect is most probably mediated through alpha-adrenergic receptors.
Clark
Kimberly A
KA
Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
Shin
Andew C
AC
Sirivelu
Madhu P
MP
Mohankumar
Sheba M J
SM
Mohankumar
P S
PS
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D018663:Adrenergic Agents; D020738:Leptin; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D007545:Isoproterenol; D003000:Clonidine; D003345:Corticosterone; D009638:Norepinephrine