Effects of Org OD 14 on pituitary and peripheral beta-endorphin in castrated rats and post-menopausal women

Abstract

The aim of the first part of this study was to evaluate the effects of a new synthetic steroid (7 alpha,17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14), on anterior pituitary (AP) and neurointermediate pituitary lobe (NIL) contents and on circulating levels of beta-endorphin (beta-EP) in rats. Three weeks after ovariectomy, groups of 9 rats were treated with either Org OD 14 (2 or 10 micrograms/day/rat for 14 days) or a placebo. In addition, 2 groups of ovariectomized rats were also treated with oestradiol benzoate (EB) (2 or 10 micrograms/day/rat for 14 days) to compare the effectiveness of the new steroid with that of a classical oestrogenic substance. beta-Ep concentrations were measured in plasma and in AP and NIL extracts by means of double-antibody radioimmunoassay (RIA), employing a specific anti-camel beta-EP (C-terminal fragment). Both doses of Org OD 14 induced a significant dose-related increase in plasma and pituitary lobe beta-EP concentrations as compared with the results on placebo treatment. By comparison, EB was active only at a dose of 10 micrograms/day. Despite the common stimulatory effects of EB and Org OD 14 on pituitary beta-EP, these findings suggest that the two steroids have different modes of action. The second part of the study investigated the changes in beta-EP and beta-lipotrophin (beta-LPH) plasma levels in a group of post-menopausal women treated for 6 months with Org OD 14 (2.5 mg/day) in comparison with the levels in a placebo-treated group. The clinical efficacy of Org OD 14 treatment in post-menopausal symptoms was confirmed, as well as its lack of or only transient effect on plasma lipids and lipoproteins. beta-EP and beta-LPH plasma levels were significantly higher in the Org OD 14-treated group than in the placebo group as from the second month until the end of the observation period.