Abstract Reinsertion of autogenous nucleus pulposus, an innovative method to delay further disc degeneration, has been proved with an experimental animal model. This study examined whether coculture of nucleus pulposus cells with annulus fibrosus cells (a) activates annulus fibrosus cells and (b) retards disc degeneration when reinserted into the disc in a rabbit model of disc degeneration. Coculture of the two cell types stimulated proliferation of each, as indicated by increased DNA synthesis measured by increases in DNA polymerase α expression and uptake of 5‐bromo‐2 deoxy‐uridine assessed by an enzyme‐linked immunosorbent assay. In a model of disc degeneration in rabbits, reinsertion of activated nucleus pulposus cells delayed the formation of clusters of chondrocyte‐like cells, the destruction of disc architecture, and the elaboration of type‐II collagen as measured immunohistochemically compared with no treatment. The direct reinsertion of activated nucleus pulposus cells into the disc offers a promising line of investigation for delaying intervertebral disc degeneration, although these results obtained with notochordal cells may not necessarily apply when mature central nucleus pulposus cells are used.
Substantial evidence has been accumulated to support the gonadal regulation of immune functions. They are mainly based on the following observations: i) the existence of sexual dimorphism in immune response, ii) alteration of immune response by gonadectomy or sex steroid replacement, iii) alteration of immune response during pregnancy, and iv) existence of sex steroid receptors in the thymus tissue which affect T cell function through thymic hormones produced in the gland. In the present study, we have tried to review some of this evidence by adding our own findings. We also referred to the experimental findings which show that the thymus, brain and gonads are close-related functionally, and form a functional axis, the so-called "hypothalamic-pituitary-gonadal-thymic" axis which is of great importance not only because it regulates immune response, but because its influence may extend to other organ system within the living body.
Proliferation of TECs in response to SHs is mediated by plasma membrane associated signal pathways generated as a result of interactions between SHs and plasma-borne inhibitors; the action of cyclins and cyclin-dependent families, such as cdc2 kinases, play a key role in cell cycle progression in TECs; the DHT in 10~(-10)mol/L enhanced the modulation of cyclin-dependent kinase families, but the 17beta-E_(2) shown as the concentration-dependent, inhibited the modulation of cyclin-dependent kinase families.
The uptake and binding of 17α,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione, a synthetic progestin, by the hypothalamus and cerebral cortex of ovariectomized oestrogen-primed rats was examined in vitro . Uptake of this steroid by the medial basal hypothalamus was higher than that by the remaining hypothalamus and cerebral cortex. The component in the cytosol from whole hypothalami which bound the radioactive progestin sedimented in the 7S region when centrifuged in a sucrose density gradient. The tritiated progestin was displaced by incubation with non-radioactive progestin or progesterone but not by oestradiol-17β, corticosterone or 5α-dihydrotestosterone (1 μmol/l). No 7S binding component was detected in a similar preparation from the cerebral cortex. The nuclear fraction from whole hypothalami extracted by KCl (0·4 mol/l) contained a progestin-binding complex which sedimented at 9S and which was heat-labile and protein in nature. It was concluded that the hypothalamus of ovariectomized oestrogen-primed rats contains progestin-binding material in the cytoplasm and progestin, bound to such material, is transported from the cytoplasm to the nucleus.
Gonadectomized male rats of Wistar strain were administered 3H-progesterone. Various brain tissues and anterior pituitary were analyzed for retention of radioactivity, using a liquid scintillation technique. Radioactivity, in all tissues, was highest at 20 min after steroid treatment, and thereafter dropped nearly in the same pattern as each other. Among the tissues examined median eminence and anterior pituitary retained more radioactivity for a longer time than did the other tissues. The results suggest that there is long-term retention of progesteronein the median eminence and anterior pituitary of male rats.
The present study was carried out to determine the direct effect of sex hormones (SHs) on thymus epithelial cell (TEC) production/secretion of the thymic hormone thymosin alpha-1 (TMA1) by using the techniques of in situ hybridization and quantitative high-performance liquid chromatography. The results were as follows: (a) the TECs which stained positive for TMA1-mRNA tended to group together, and TMA1-mRNA expression was observed exclusively in their cytoplasm; (b) at doses over 3 × 10−9 M estradiol-17β(E2β) caused a progressive loss of the number of TMA1-mRNA-positive cells, whereas 5α-dihydrotestosterone (5α-DHT) did not affect the cell number at all; (c) the degree of TMA1-mRNA expression decreased significantly at increasing concentrations of E2 β over 3 × 10−12 M and 5α-DHT over 3 × 10−10 M; (d) the production of TMA1 by TECs was significantly inhibited by increasing concentrations of E2 β over 3 × 10−11 M and 5α-DHT over 3 × 10−10 M. The above results clearly indicate that SHs, especially E2 β, directly modulate TECs to produce the thymic hormone TMA1 probably through their receptor mechanism.
