The effect of leptin on luteinizing hormone release is exerted in the zonaincerta and mediated by melanin-concentrating hormone

The adipose hormone, leptin, not only restrains appetite, but also influenc es energy expenditure. One such influence is to promote sexual maturation a nd fertility. The neuromodulatory circuits that mediate this effect are not well known but the present study suggests that one mediator could be melan in-concentrating hormone (MCH). We show that the long-form receptor (Ob-Rb) is expressed in the zona incerta of the rat and that administration of lep tin (both 0.5 mu g and 1.0 mu g/side) into this area of ovariectomized, oes trogen-primed rats stimulated the release of luteinizing hormone (LH) withi n 1 h, the effect enduring for a further 1 h. Injections of leptin into the arcuate nucleus induced a smaller, transient rise in LH while injections i nto the paraventricular and ventromedial nuclei were without effect. MCH ne urones are present in the zona incerta and administration of this hormone i nto the medial preoptic area (mPOA) stimulates LH release, therefore we inv estigated the possibility that MCH might mediate this effect of leptin. An injection of MCH antiserum into mPOA prevented the rise in LH normally indu ced by leptin injected into the zona incerta. In addition, melanocortin rec eptor antagonists ([D-Arg(8)]ACTH(4-10) and [Ala(6)]ACTH(4-10)), previously shown to inhibit the stimulatory effect of MCH on LH release, also inhibit ed the effect of leptin. We propose that one route by which leptin may prom ote reproductive activity is by enhancing MCH release from fibres within th e mPOA. Speculative mechanisms for the action of MCH include the following possibilities: MCH may be acting on the specific MCH receptor which in turn interacts with a melanocortin or melanocortin-like receptor; MCH may bind directly to one of the melanocortin receptors; or melanocortin antagonists may interact with the MCH receptor.