The endometrium as a novel target for leptin: differences in fertility andsubfertility

Leptin and its receptor are involved in endocrine and paracrine regulation of metabolism, obesity and reproduction. Here, we describe the detection of the functional long isoform receptor of leptin in human endometrium. The l eptin receptor protein was shown to be expressed in glandular and luminal e pithelium and is periodically regulated throughout the menstrual cycle, dem onstrating main expression in follicular and mid-luteal phase. In contrast, leptin receptor mRNA is detectable by reverse transcription-polymerase cha in reaction (RT-PCR) as a constitutive component. Since RT-PCR analyses sho wed that leptin is not expressed in this tissue, the present study suggests that the human endometrium is a novel target for leptin. Therefore, we inv estigated 11 subfertile patients who underwent two biopsies in one menstrua l cycle. The patients presented with a repetitive endometrial maturation de fect, but showed adequate serum hormone concentrations and normal steroid h ormone receptor expression and down-regulation in the endometrium. These pa tients were, however, deficient for expression of the functional leptin rec eptor. These analyses provide evidence that the lack of the leptin receptor in an ovulatory cycle may contribute to subfertility by a yet undefined 'e ndometrial factor'.