J Korean Med Sci.  2009 Aug;24(4):729-736. 10.3346/jkms.2009.24.4.729.

Comparative Study of the Effects of Different Growth Hormone Doses on Growth and Spatial Performance of Hypophysectomized Rats

• Kwak MJ
• Park HJ
• Nam MH
• Kwon OS
• Park SY
• Lee SY
• Kim MJ
• Kim SJ
• Paik KH
• Jin DK

• KMID: 1779211
• DOI: http://doi.org/10.3346/jkms.2009.24.4.729

Abstract

This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 microgram/kg of GH once daily for 9 days; group 2, administered 200 microgram/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.

Keyword

Growth Hormone; Hypophysectomized Rat; Somatic Growth; Cognitive Function; Morris Water Maze Test

MeSH Terms

Animals
Body Weight
Female
Growth/*drug effects
Growth Plate/drug effects/pathology
Human Growth Hormone/administration & dosage/*pharmacology
Humans
*Hypophysectomy
Rats
Rats, Sprague-Dawley
Spatial Behavior/*drug effects

Figure

• 

  Fig. 1 The automated tracking system (Smart v.20®) used in the Morris water maze (MWM) test. There is a circular platform in the one of the quadrants. The 3 quadrants except the target quadrant that contained the hidden platform were used for entry during each trial on a particular day. The escape latency (the time taken to reach the hidden platform), the length of the swim path, and the swimming speed were measured automatically.

• 

  Fig. 2 Effects of rhGH on body weight of HYPOX rats. Body weights were measured over 10 days. GH was administered for 9 days. Weight gain in each group was analyzed using the Wilcoxon signed-ranks test. A significant weight gain was evident only in groups 1 and 2. Data are represented as the median and interquartile ranges (5 rats per group). Group 1: rhGH 200 µg/kg subcutaneously once daily, P=0.042. Group 2: rhGH 200 µg/kg subcutaneously twice daily, P=0.043. Group 3: Saline subcutaneously once daily, P=1.000.

• 

  Fig. 3 Representative stained sections of the tibial growth plates of HYPOX rats. Arrows indicate the width of the proximal tibial growth plate. (A) Group 1: rhGH 200 µg/kg subcutaneously once daily, (B) Group 2: rhGH 200 µg/kg subcutaneously twice daily, (C) Group 3: Saline subcutaneously once daily. The width of the tibial growth plate is thicker in B than in A and C (P=0.040 and P=0.005, respectively) (H&E stained, ×100).

• 

  Fig. 4 Effects of rhGH treatment of HYPOX rats on performance in the MWM test from experimental days 5 to 9. The training was carried out in 1 block of 3 trials per day for 5 consecutive days. Improvements in the performance in the MWM test were evaluated using the Wilcoxon signed-ranks test (Group 1, P=0.080; Group 2, P=0.043; Group 3, P=0.043). *P=0.027, using Kruskal-Wallis test with Bonferroni's correction. The data obtained on day 7 were subjected to a multiple comparison test was performed using LSD. Data are represented as the median and interquartile ranges (5 rats per group). On day 7, Group 1 vs. Group 2: P=0.023. Group 1 vs. Group 3: P=0.000. Group 2 vs. Group 3: P=0.032. Group 1: rhGH 200 µg/kg subcutaneously once daily. Group 2: rhGH 200 µg/kg subcutaneously twice daily. Group 3: Saline subcutaneously once daily.

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