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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 Men¹

Department of Medicine, Santiago de Compostela University, Endocrine Section (X.C., V.P., R.P., M.L., J.C., F.F.C.), the Department of Morphological Sciences (R.G.), and the Department of Physiology (C.D.), University of Santiago de Compostela; and the Division of General Surgery (L.G.V.), Hospital de Conxo, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain

Address all correspondence and requests for reprints to: F. F. Casanueva, M.D., Ph.D., P.O. Box 563, Santiago de Compostela E-15780, Spain. E-mail: meffcasa{at}uscmail.usc.es

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves.

To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 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 expressed as the mean ± SEM of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h).

Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 ± 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 ± 323). Coincubation of adipose tissue with 1 µmol/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 tissue with 1 µmol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 ± 688; n = 9), whereas it did not alter the secretion in the male samples (3373 ± 444; n = 6). In samples from both sexes, coincubation with 1 µmol/L estrone or progesterone had no effect, whereas 1 µmol/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 women than in samples from men, 2) is stimulated by dexamethasone and estradiol 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 genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.

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