GENDER DIFFERENCES IN BOTH SPONTANEOUS AND STIMULATED LEPTIN SECRETION BY HUMAN OMENTAL ADIPOSE-TISSUE IN-VITRO - DEXAMETHASONE AND ESTRADIOL STIMULATE LEPTIN RELEASE IN WOMEN, BUT NOT IN MEN

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulatin g leptin mainly reflects both total fat mass and the size of constitue nt adipocytes, although other ancillary hormonal factors may contribut e to its blood concentration. Relevant gender differences in leptin co ncentrations have been reported, but it is not clear whether the eleva ted leptin levels in women are an intrinsic property of their adipocyt es or merely reflect a greater amount of fat reserves. To clarify thes e points, a systematic study with organ culture from human omental adi pose tissue either stimulated or not with steroid hormones was underta ken in samples obtained at surgery from 67 nonobese donors (33 women a nd 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expre ssed as the mean +/- SEM of the integrated secretion to the medium (ar ea under the curve; nanograms of leptin per g tissue/48 h). Control no nstimulated samples showed a steady leptin secretion along the 96 h st udied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin se cretion in samples from 33 women (3904 +/- 347) was significantly high er (P < 0.05) than that in samples from 34 men (2940 +/- 323). Coincub ation of adipose tissue with 1 mu mol/L dexamethasone induced a clear- cut leptin increase (P ( 0.05) in samples from women(5848 +/- 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 +/- 741; n = 6). Similarly, coincubation of adipose tis sue with 1 mu mol/L estradiol induced a notable leptin increase (P < 0 .05) in samples from women (5698 +/- 688; n = 9), whereas it did not a lter the secretion in the male samples (3373 +/- 444; n = 6). In sampl es from both sexes, coincubation with 1 mu mol/L estrone or progestero ne had no effect, whereas 1 mu mol/L forskolin significantly (P < 0.05 ) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from wo men than in samples from men, 2) is stimulated by dexamethasone and es tradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both gende rs. This different response to the stimulation of adipose tissue may b e the biological basis for the gender differences observed in circulat ing levels of human leptin.