REGIONAL DIFFERENCES AND UP-REGULATION OF PROGESTERONE RECEPTORS IN ADIPOSE TISSUES FROM ESTROGEN-TREATED SHEEP

Differing risk factors between men and women for a number of vascular and metabolic diseases have been linked to regional obesity. The diffe rences in the distribution of adipose tissues between men (abdominal o r upper-body obesity) and women (gluteal/femoral or lower body obesity ) suggest a role for sex steroids in the regional distribution of fat. Previous work from this laboratory has shown the presence of oestroge n receptor (ER) in gluteal, perirenal and omental adipose tissues of e wes with similar physical characteristics to the ER in uterine tissue. The concentration profile for adipose ER was gluteal> perirenal>oment al. In this report, we determined the physiological significance of ad ipose ERs by showing an up-regulation of the progesterone receptor (PR ) in adipose tissues after oestrogen treatment in a fashion similar to that seen in a major responsive tissue such as uterus. Using PR antib odies (PR-6 and C-262), Western blot analysis of PR from oestrogen-tre ated sheep indicated that PR was induced in uterus>>>gluteal adipose>p erirenal adipose consistent with the concentration of ER contained in these tissues. PR could not be detected by Western blotting in omental adipose tissue from oestrogen-treated animals or in gluteal, perirena l and omental adipose tissues from untreated animals. Sucrose gradient profiles of progestin (R-5020) binding ti-om uterus and gluteal adipo se tissues of oestrogen-treated ewes showed specific binding in both t he 5S and 9S regions of the gradient, while perirenal and omental adip ose tissue had only the 5S peak. The amount of specific binding was in creased with oestrogen treatment in all the tissues. When gluteal adip ose tissue cytosol was preincubated with PR antibody (C-262) to preven t binding of ligand and subjected to sucrose gradient analysis, both t he 5S and 9S regions were diminished, suggesting that both peaks conta ined PR. Dilution of uterine cytosol resulted in an increase in the ra tio of the 5S to the 9S peak, indicating that the 9S PR complex dissoc iates at low concentrations; this may be the reason why only the 5S pe ak was observed in perirenal and omental adipose tissues. These data o ffer further support for a direct role of sex steroids in regional adi pose accretion and metabolism.