1. ¹Division of Geriatric Health and Nutrition, National Institute of Health and Nutrition, Japan
2. ²First Department of Internal Medicine, Showa University School of Medicine, Japan
3. ³Department of Applied Biology, Faculty of Textile Science, Kyoto Institute of Technology, Japan
4. ⁴Laboratory of Health Science, School of Pharmaceutical Sciences, University of Shizuoka, Japan
5. ⁵Department of Anatomy, Showa University School of Medicine, Japan
6. ⁶Department of Nutrition and Physiology, Faculty of Home Economics, Kyoritsu Women's University, Tokyo, Japan

Correspondence: Dr S Inoue, Department of Nutrition and Physiology, Faculty of Home Economics, Kyoritsu Women's University, 2-2-1 Hitotsubashi, Chiyoda-ku, Tokyo 101-8433, Japan. E-mail: ishuji@s1.kyoritsu-wu.ac.jp

Received 8 October 2002; Revised 30 January 2003; Accepted 6 March 2003.

Abstract

BACKGROUND: We demonstrated that ventromedial hypothalamus (VMH) lesions facilitate DNA synthesis, which reflects cell proliferation in abdominal organs, including the liver, pancreas, stomach, small intestine and large intestine, all of which are amply innervated by the vagal nerve.

OBJECTIVE: To investigate which area DNA synthesis facilitates and what factors contribute to cell proliferation in the small intestine in VMH-lesioned rats.

DESIGN: At 7 days after VMH lesions or sham operations, a segment of rat jejunum was taken for histological examination. A part of the jejunum was also removed from VMH-lesioned and sham-operated rats after 3 days and examined for 5-bromo-2'-deoxyuridine (BrdU) incorporation. At 6, 12 and 24 h after VMH lesions, the proximal intestine was removed from individual rats, from the pylorus to the mid-jejunum. Total RNA was extracted from these tissues of each rat, and the levels of epidermal growth factor (EGF) and transforming growth factor (TGF)- mRNA were determined using reverse-transcription polymerase chain reaction. Cyclooxygenase (COX)-1 and -2 mRNA levels were determined using Northern blotting.

RESULTS: Jejunal villi in VMH-lesioned rats were markedly enlarged compared to those of sham-operated rats and jejunal crypts in VMH-lesioned rats more markedly incorporated BrdU. Northern blot analysis revealed an increase in COX-1 mRNA after 6, 12 and 24 h in the jejunum of VMH-lesioned rats. COX-2 mRNA was decreased 6 and 12 h after VMH lesioning; however, it was significantly increased 24 h after VMH lesions in comparison to sham-operated rats. The levels of EGF and TGF- mRNA were unchanged in VMH lesioned rats.

CONCLUSION: VMH lesions induced enlargement of jejunal villi and increased the gene expression of COX-1 in the small intestine. Prostaglandins, probably E₂, induced by COX-1 may be one candidate factor responsible for the cell proliferation of the small intestinal epithelium in these rats.