The relative affinities of the 1 alpha,25-dihydroxyvitamin D3 (1,25-D3) analogues 20-epi-1 alpha,25-dihydroxyvitamin D3 (IE) and 20-epi-22-oxa-24a,26a,27a-tri-homo-1 alpha,25-dihydroxyvitamin D3 (ID) to the nuclear vitamin D receptor (VDR) are similar to that of 1,25-D3, but their antiproliferative action is 1000-fold greater. We tested whether the greater antiproliferative effect of these analogues is due to a differential activation of the VDR. In ROS 17/2.8 cells, the effective doses required to produce 50% maximal stimulation (ED50) of transfected reporter genes driven by either the osteocalcin or the osteopontin vitamin D-response elements (VDRE) were 5 x 10(-9) M, 10(-10) M, and 10(-11) M for 1,25-D3, ID, and IE, respectively. Similar results were obtained when recombinant human VDR was cotransfected into CV-1 cells with an osteocalcin VDRE-reporter plasmid. We found that in vitro the sensitivity of 1,25-D3-induced and analogue-induced receptors to proteases was different. The ED50 for binding to VDRE, as determined by electrophoretic mobility shift assays, was significantly higher for 1,25-D3-induced than for analogue-induced VDR. The concentration of retinoid X receptor (RXR) was significantly lower in 1,25-D3-induced than analogue-induced VDR complexes with VDRE. We therefore conclude that IE and ID augment transcriptional activity of VDR more than 1,25-D3 does, by producing conformational changes that enhance dimerization of VDR with RXR. We suggest that these conformational changes are due to differences in the contact sites of the 20-epi analogues and 1,25-D3 with the VDR.

The ovaries of Hipposideros speoris were studied histologically and histochemically for the enzymes, 3β-hydroxysteriod dehydrogenase (3β-HSDH), Succinic dehydrogenase (SDH) and lipid from July 2005 to 2006. The interstitial cells or so called "epithelial cords" showed variations in their distribution, morphology, enzymic and their association with other ovarian structures. These cords appear to be formed in the ovarian cortex by the transformation of granulosa of the primordial follicles and small preantral follicles whose ova regress and disappear. Mostly these cords were conspicuous, hypertrophied, abundant and in clusters or in zones occupying a major portion of the cortex during 4 to 5 months of gestation and also during lactation. Both histological and histochemical studies revealed their significance as steroidogenic cells. The frequency with which these structures were observed during pregnancy made it obligatory to conclude that they have a certain significant role in ovarian physiology in overtaking the function of corpus luteum after its regression.

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