In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin(116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis. neuroendocrine function and fertility. Identifi cation of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful t ool for detailed characterization of the biological actions of leptin in di fferent experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a c ontinuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis ill vitro. Tn addition, a comparison of the e ffects of human recombinant leptin and leptin(116-130) amide at the pituita ry level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7) M) significantly inhibited both basal and human chorionic gonadotrophin (hCG) -stimulated testosterone secretion in vitro. Similarly, incubation of testi cular tissue in the presence of increasing concentrations of leptin(116-130 ) amide (10(-9)-10(-5) M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7) M upwards. In addition, leptin(116-130) amide, at al l doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secreti on by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin( 10(-9)-10(-7) M) was ineffe ctive in modulating LH and FSH release. Finally. neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion i n vitro. Our results confirm the ability of leptin, acting at the testicula r level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. I n addition, we provide evidence for a direct inhibitory action of leptin(11 6-130) amide on pituitary LH and FSH secretion, a phenomenon not observed f or the native leptin molecule, in the adult male rat.