The obese gene (ob) product,
leptin, has recently emerged as a key
element in
body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the
leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the
biological actions of
leptin in different 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 continuation 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 in vitro. In addition, a comparison of the effects of human recombinant
leptin and
leptin(116-130) amide at the pituitary 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 testicular 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 all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant
leptin nor
leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of
leptin, acting at the testicular 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. In addition, we provide evidence for a direct inhibitory action of
leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native
leptin molecule, in the adult male rat.