Evaluation of the role of melanocortin 3 and 4 receptors in leptin-stimulated and spontaneous growth hormone secretion in rats.
It has been reported that the melanocortin 4-receptor (MC4-R) may act downstream of leptin to mediate its effects on food intake and several neuroendocrine functions (the reproductive system, the hypothalamo-pituitary-thyroid axis, and prolactin secretion). However, no previous study examined whether MC4-R mediates leptin stimulatory actions on growth hormone (GH) secretion, or whether MC4-R signaling is involved in spontaneous pulsatile GH release in fed rats. Therefore in this study we examined the involvement of both MC3-R and MC4-R (the predominant MC-R subtypes expressed in the brain) in these two aspects of GH secretion in freely-moving male rats. In both fed and 3-day fasted rats, plasma GH levels were determined every 15 min over 5 h after single intracerebroventricular injections of the following substances or vehicle. Fasting diminished and leptin (0.3 nmol) reinstated the GH pulse amplitude without affecting the pulse frequency. Neither HS014 (1.0 nmol, a selective MC4-R antagonist) nor agouti-related peptide (1.0 nmol, a non-selective MC3/4-R antagonist) was effective in altering leptin-stimulated or spontaneous GH secretion. In addition, neither melanotan-II (1.0 nmol, a non-selective MC3/4-R agonist) nor gamma(1)-melanocyte-stimulating hormone (10 nmol, a selective MC3-R agonist) affected significantly GH release in fasted rats. We have previously demonstrated that stimulation or blockade of MC4-R, achieved by the same drug dosage as in this study, significantly affect luteinizing hormone and prolactin secretion in rats. The present results thus suggest that neither MC4-R nor MC3-R is involved in leptin-stimulated or spontaneous GH secretion, or at least that the level of MC4-R involvement in GH secretion is much lower than that in luteinizing hormone and prolactin release regulation.
Watanobe
Hajime
H
Division of Internal Medicine, Clinical Research Center, International University of Health and Welfare, Otawara, Tochigi, Japan. watah@iuhw.ac.jp
Yoneda
Masashi
M
D000818:Animals; D004435:Eating / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D008297:Male; D011673:Pulsatile Flow; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3 / Q000502:physiology*; D044105:Receptor, Melanocortin, Type 4 / Q000502:physiology*
D020738:Leptin; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D013006:Growth Hormone