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Sex Difference in the Response of Melanin-Concentrating Hormone Neurons in the Lateral Hypothalamic Area to Glucose, as Revealed by the Expression of Phosphorylated Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein

Department of Neuroendocrinology (K.M., T.F., D.M., H.H., F.K.), Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama 236-0004; and International University of Health and Welfare (F.K.), Amity-Nogizaka Minamiaoyama, Minato-ku, Tokyo 107-0062, Japan

Address all correspondence and requests for reprints to: Dr. Toshiya Funabashi, Department of Neuroendocrinology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. E-mail: toshiya{at}med.yokohama-cu.ac.jp.

Because there are sex differences in feeding behavior in rats, we looked for a possible sex difference in the response to glucose of melanin-concentrating hormone (MCH) neurons in the lateral hypothalamic area using phosphorylated cAMP response element-binding protein (pCREB) as a marker of neural activity. Intact male rats and female rats at diestrus 2, proestrus, or estrus were fed normally or fasted for 48 h and injected with saline or glucose (400 mg/kg). Thereafter, preparations were subjected to immunohistochemical processing for the double staining of MCH and pCREB. Fasting increased the ratio of MCH neurons with pCREB (double-stained cells) in both male and female rats. In fasted rats, glucose injection decreased the ratio of double-stained cells more promptly in females than in males. The magnitude of decrease caused by glucose was greater at proestrus and estrus than at diestrus 2. Gonadectomy in males enhanced and in females attenuated the response of MCH neurons to glucose. Testosterone and estrogen replacement in males and females, respectively, restored the response of MCH neurons to glucose. The demonstrated sex differences in the response of MCH neurons to glucose correlated well with the gonadal steroid milieu; thus, MCH neurons may play an important role in sex differences in feeding behavior.

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