ESTROGEN ANTAGONISM ON T-3 AND GROWTH-HORMONE CONTROL OF THE LIVER MICROSOMAL LOW-AFFINITY GLUCOCORTICOID BINDING-SITE (LAGS)

Male rat liver microsomes contain a low-affinity glucocorticoid bindin g site (LAGS) capable of binding all natural glucocorticoids and proge sterone with a K-d from 20 to 100 nM. The LAGS level is under endocrin e control by T-3, glucocorticoids and GH. These hormones act synergist ically at physiological concentrations to increase the LAGS level. Sin ce female rats show a LAGS level that is much lower than the males (0. 15 vs 23 pmol/mg protein, respectively), here we investigated whether estradiol could decrease the LAGS in the male rat. Orchiectomized (OX) male rats showed a higher LAGS level than intact rats. This effect wa s reversed by implanting a Sylastic capsule containing testosterone. W hen the OX rats were implanted for 20 days with estrogen capsules that provided an estradiol level in serum of 40 pg/ml, their LAGS level de creased from 23 to 0.2 pmol/mg protein. This effect was not observed i n intact male rats and can be partially reversed by testosterone impla nts into OX rats. Both hypophysectomized male rats and hypothyroid-orc hiectomized male rats showed very low levels of LAGS. Administration o f physiological doses of GH and/or T-3 to these rats greatly increased their LAGS level (from 0.3 to 15 and 16 pmol/mg protein, respectively ). Implantation of estrogen capsules to these rats two weeks prior to starting treatment completely inhibited the increase in the LAGS level in response to T-3, and significantly decreased the response to hGH, and to a combination of hGH and T-3. These results suggest that physio logical estradiol levels call antagonize the LAGS induction by T-3 and hGH in the male rat, and could be responsible for the low level of LA GS in the female rat. Moreover, estrogen capsules also inhibited the i ncrease in the body and hepatic weights observed after hGH treatment, which suggests a powerful inhibitory effect of low estradiol levels on the male rat liver functions under regulation by T-3 and/or GH. (C) 1 997 Elsevier Science Ltd. All rights reserved.