Ms. Erskine et S. Miller, ULTRASTRUCTURAL EFFECTS OF ESTRADIOL AND 5-ALPHA-ANDROSTANE-3-ALPHA, 17-BETA-DIOL ON NEURONS WITHIN THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS, Neuroendocrinology, 61(6), 1995, pp. 669-679
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.