ULTRASTRUCTURAL EFFECTS OF ESTRADIOL AND 5-ALPHA-ANDROSTANE-3-ALPHA, 17-BETA-DIOL ON NEURONS WITHIN THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS

The metabolite of dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Diol), is a potent inhibitor of estrogen-induced go nadotropin and prolactin secretion and lordosis behavior in the female rat. This study examined whether 3 alpha-Diol can counteract the ultr astructural changes which are known to occur in the ventromedial nucle us (VMN) of the hypothalamus following estrogen treatment. Ovariectomi zed rats were treated with estradiol (E(2); n = 7), 3 alpha-Diol (n = 5), E(2) and 3 alpha-Diol (n = 6), or received control (n = 6) treatme nts. E(2) was administered in subcutaneous capsules for two discontinu ous 2-hour periods separated by 5 h, a 'pulsed' treatment regimen know n to mimic the timing of endogenous E(2) action and to influence neuro nal ultrastructure in the VMN. Animals given 3 alpha-Diol received sub cutaneous injections (6 mg/kg) 3 h prior to each implantation of E(2) or empty capsules. Control animals received vehicle 3 h prior to impla ntation of blank capsules. Animals were perfused 24 h after initial ho rmone treatment and neurons from the ventrolateral portion of the VMN were examined using electron microscopy. Separately, both E(2) and 3 a lpha-Diol treatment increased somal and nuclear size, altered somal an d nuclear shape, and increased the numbers of lysosomes present in the cytoplasm above control levels. E(2) treatment resulted in increased stacking of the rough endoplasmic reticulum while 3 alpha-Diol treatme nt resulted in an unusual plexiform rough endoplasmic reticulum distri bution. In contrast, combined treatment with E(2) and 3 alpha-Diol res ulted in cells which were similar to ovariectomized control cells on t hese measures. All steroid treatments decreased the amount of heteroch romatin present within the nucleus compared to that seen in controls. Thus, 3 alpha-Diol influences the ultrastructural characteristics of n eurons within the VMN in a manner somewhat though not altogether simil ar to E(2). However, 3 alpha-Diol given in combination with E(2) count eracts or prevents the actions of E(2) within these same neurons.