Fig. 1.

Orexigenic effect of growth hormone (GH) via activation of agouti-related protein (AgRP) neurons. a, b Photomicrographs showing the hypothalamic distribution of signal transducer and activator of transcription 5 (STAT5) phosphorylation (pSTAT5) 90 min after an intraperitoneal (i.p.) injection of phosphate-buffered saline (PBS) or porcine GH (20 µg/g body weight (b.w.)). 3V third ventricle, ARH arcuate nucleus, DMH dorsomedial nucleus, fx fornix, LHA lateral hypothalamic area, VMH ventromedial nucleus. Scale Bar = 200 µm. c More than 90% of AgRP neurons (red) in the ARH are responsive to porcine GH as indicated by the co-expression of pSTAT5 (green). Yellow represents double-labeled cells. Scale Bar = 50 µm. d Intracerebroventricular (i.c.v.) infusion of porcine GH (6 µg in 2 µL) increased food intake (0.5 h: t₍₈₎ = 1.258, P = 0.244; 1 h: t₍₈₎ = 2.075, P = 0.0717; 2 h: t₍₈₎ = 1.425, P = 0.1919; 4 h: t₍₈₎ = 1.518, P = 0.1675; 24 h: t₍₈₎ = 2.801, P = 0.0232; n = 9), compared to the infusion of artificial cerebrospinal fluid (aCSF). e The i.c.v. infusion of porcine GH reduced energy expenditure (t₍₅₎ = 3.193, P = 0.0242, n = 6; paired t-test) of C57BL/6 mice. f Hypothalamic gene expression in C57BL/6 mice that received i.p. infusion of either PBS or porcine GH (AgRP: t₍₁₅₎ = 2.723, P = 0.0157; neuropeptide Y (NPY): t₍₁₅₎ = 2.144, P = 0.0488; proopiomelanocortin (POMC): t₍₁₄₎ = 0.5188, P = 0.612; n = 9; unpaired t-test). g Representative whole-cell patch-clamp recording of a GH responsive AgRP neuron. Dashed line indicates the resting membrane potential. Porcine GH (5 µg/mL) was applied to the bath for approximately 5 min. h, i Increased resting membrane potential (t₍₂₎ = 4.768, P = 0.0413; paired t-test) and firing rate (t₍₂₎ = 3.001, P = 0.0477; paired t-test) of GH-responsive AgRP neurons (n = 3). j AgRP growth hormone receptor knockout (GHR KO) mice showed very few GH-induced pSTAT5 (green) in AgRP neurons (red). Scale Bar = 50 µm. All results were expressed as mean ± s.e.m. *P < 0.05