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Sex Difference in Hepatic Peroxisome Proliferator-Activated Receptor Expression: Influence of Pituitary and Gonadal Hormones

Department of Physiology and Pharmacology (M.J., L.C., C.A., D.L., A.L., S.E., J.O.), Göteborg University, Göteborg S-405 30, Sweden; and Institute de Biologie Animale (L.M., W.W.), Faculté des Sciences, Lausanne CH-1015, Switzerland

Address all correspondence and requests for reprints to: Jan Oscarsson, Department of Physiology, Göteborg University, Box 434, S-405 30 Göteborg, Sweden. E-mail: Jan.Oscarsson{at}fysiologi.gu.se.

Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor that is mainly expressed in tissues with a high degree of fatty acid oxidation such as liver, heart, and skeletal muscle. Unsaturated fatty acids, their derivatives, and fibrates activate PPAR. Male rats are more responsive to fibrates than female rats. We therefore wanted to investigate if there is a sex difference in PPAR expression. Male rats had higher levels of hepatic PPAR mRNA and protein than female rats. Fasting increased hepatic PPAR mRNA levels to a similar degree in both sexes. Gonadectomy of male rats decreased PPAR mRNA expression to similar levels as in intact and gonadectomized female rats. Hypophysectomy increased hepatic PPAR mRNA and protein levels. The increase in PPAR mRNA after hypophysectomy was more pronounced in females than in males. GH treatment decreased PPAR mRNA and protein levels, but the sex-differentiated secretory pattern of GH does not determine the sex-differentiated expression of PPAR. The expression of PPAR mRNA in heart or soleus muscle was not influenced by gender, gonadectomy, hypophysectomy, or GH treatment. In summary, pituitary-dependent hormones specifically regulate hepatic PPAR expression. Sex hormones regulate the sex difference in hepatic PPAR levels, but not via the sexually dimorphic GH secretory pattern.

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