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Leptin Inhibits in Vitro Hypothalamic Somatostatin Secretion and Somatostatin mRNA Levels

Department of Physiology (M.Q., R.S., C.D.) and Department of Medicine, Endocrine Area Complejo Hospitalario Universitario de Santiago (F.F.C.), University of Santiago, Santiago de Compostela (Spain); Division of Endocrinology (M.L.H.), Lilly Research Laboratories, Indianapolis, Indiana

Address all correspondence and requests for reprints to: Dr. C. Dieguez, Universidad de Santiago de Compostela, Departamento de Fisioloxia, P.O. Box 563, Santiago de Compostela, E-15700 Spain.

	Abstract

Top Abstract

 
Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. The site of action of leptin is likely to be the hypothalamus, since this area is important in the control of food intake and leptin receptor mRNA is particularly abundant in this area. In order to further unravel the mechanisms by which leptin acts, we have studied the effect of leptin on in vitro somatostatin synthesis and secretion.

Leptin administration to fetal rat neurones in monolayer culture led to a time dependent decrease in basal somatostatin secretion and somatostatin mRNA levels, the maximal effect being observed with 6 x 10^-8 M leptin after 24 h incubation. Furthermore, leptin completely blunted 10^-7 M Neuropeptide Y-induced increase in somatostatin secretion and somatostatin mRNA levels as well as 10^-3 M (Bu)₂-cAMP and 10^-6 M A23187-induced somatostatin secretion. Finally, leptin (3 x 10^-8 M) also inhibited low glucose (1.1 mM) induced-somatostatin secretion in perifused adult hypothalami. This data indicates that leptin can influence the neuroendocrine system by regulating hypothalamic somatostatin gene expression.

Received April 2, 1997.

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