Leptin Actions on the Reproductive Axis

Paolo Magni, Luciano Martini and Marcella Motta

Institute of Endocrinology University of Milan 20133 Milan, Italy

To the editor:

We read with interest the comprehensive editorial by Hileman et al. (1) entitled "Leptin, nutrition, and reproduction: timing is everything," which appeared in JCEM. The paper extensively revises the pleiotropic actions of leptin with particular emphasis on the involvement of this hormone in the regulation of energy metabolism and of the reproductive axis. The authors underline that "although leptin clearly influences reproduction, where leptin acts to exert its effects is not yet resolved." This remains a still not fully clarified aspect of leptin physiology. According to studies mentioned in the paper, leptin has been found to stimulate both GnRH and LH release from hypothalamic and pituitary explants, respectively (2). These data suggest that leptin may act at the hypothalamic level, but leave open the question of whether it acts directly or indirectly (or both) on GnRH neurons. On this aspect, the authors comment that "to date, leptin receptors have not been identified on GnRH neurons," according to some studies performed on brain tissue (3). This observation, however, should be revisited in light of our study published in Endocrinology (5). In this paper, we report that leptin receptors are expressed in mouse immortalized GnRH neurons and that these receptors seem to be functional in modulating GnRH secretion (5). These data, thus, suggest the possibility that leptin may also regulate GnRH secretion by acting directly at the hypothalamic level. GT1 immortalized GnRH neurons represent a well-established in vitro system for studying the control of GnRH secretion (6). This model system seems very useful, since the study of the regulation of GnRH secretion is difficult to perform in vivo, due to the fact that GnRH-secreting neurons are quite few and scattered through the hypothalamic region. The utilization of GT1 immortalized GnRH neurons has generated a large body of papers that have appeared in the most important endocrinological journals. Additional studies seem, however, still necessary to fully clarify this issue in vivo and in the different species.

Received July 19, 2000.

References

  1. Hileman SM, Pierroz DD, Flier JS. 2000 Leptin, nutrition, and reproduction: timing is everything. J Clin Endocrinol Metab. 85:804–807.[Free Full Text]
  2. Yu WH, Kimura M, Walczewska A, Karanth S, McCann SM. 1997 Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci USA. 94:1023–1028.[Abstract/Free Full Text]
  3. Hakansson M-L, Brown H, Ghilardi N, Skoda RC, Meister B. 1998 Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci. 18:559–572.[Abstract/Free Full Text]
  4. Finn PD, Cunningham MJ, Pau K-YF, Spies HG, Clifton DK, Steiner RA. 1998 The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey. Endocrinology. 139:4652–4662.[Abstract/Free Full Text]
  5. Magni P, Vettor R, Pagano C, et al. 1999 Expression of a leptin receptor in immortalized GnRH-secreting neurons. Endocrinology. 140:1581–1585.[Abstract/Free Full Text]
  6. Mellon P, Windle J, Goldsmith P, Padula C, Roberts J, Weiner R. 1990 Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron. 5:1–10[Medline]




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