Ultrastructural Effects of Estradiol and 3α-Androstane-3α,17β-diol on Neurons within the Ventromedial Nucleus of the Hypothalamus

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Abstract
The metabolite of dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Diol), is a potent inhibitor of estrogen-induced gonadotropin and prolactin secretion and lordosis behavior in the female rat. This study examined whether 3 alpha-Diol can counteract the ultrastructural changes which are known to occur in the ventromedial nucleus (VMN) of the hypothalamus following estrogen treatment. Ovariectomized rats were treated with estradiol (E2; n = 7), 3 alpha-Diol (n = 5), E2 and 3 alpha-Diol (n = 6), or received control (n = 6) treatments. E2 was administered in subcutaneous capsules for two discontinuous 2-hour periods separated by 5 h, a 'pulsed' treatment regimen known to mimic the timing of endogenous E2 action and to influence neuronal ultrastructure in the VMN. Animals given 3 alpha-Diol received subcutaneous injections (6 mg/kg) 3 h prior to each implantation of E2 or empty capsules. Control animals received vehicle 3 h prior to implantation of blank capsules. Animals were perfused 24 h after initial hormone treatment and neurons from the ventrolateral portion of the VMN were examined using electron microscopy. Separately, both E2 and 3 alpha-Diol treatment increased somal and nuclear size, altered somal and nuclear shape, and increased the numbers of lysosomes present in the cytoplasm above control levels. E2 treatment resulted in increased stacking of the rough endoplasmic reticulum while 3 alpha-Diol treatment resulted in an unusual plexiform rough endoplasmic reticulum distribution. In contrast, combined treatment with E2 and 3 alpha-Diol resulted in cells which were similar to ovariectomized control cells on these measures. All steroid treatments decreased the amount of heterochromatin present within the nucleus compared to that seen in controls. Thus, 3 alpha-Diol influences the ultrastructural characteristics of neurons within the VMN in a manner somewhat though not altogether similar to E2. However, 3 alpha-Diol given in combination with E2 counteracts or prevents the actions of E2 within these same neurons.

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