286 research outputs found
Interactions between type 1 astrocytes and LHRH-secreting neurons (GT1-1 cells) : modification of steroid metabolism and possible role of TGFβ1
No full textThe hypothesis that type 1 astrocytes (A1) might modify the activities of the enzymes 5 alpha-reductase (5 alpha-R) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) present in the GT1-1 cells has been tested. The data obtained indicate that, utilizing a co-culture technique, A1 are able to: (1) decrease the formation of dihydrotestosterone (DHT) from testosterone (T), (2) increase the formation of dihydroprogesterone (DHP) from progesterone (P); (3) decrease the conversion of DHP into tetrahydroprogesterone (THP) in GT1-1 cells. Moreover, GT1-1 cells are able to increase the formation of DHP in Al; that of DHT was unchanged. The present data might suggest the possible existence of a third isoform of the enzyme 5 alpha-R; details on this hypothesis are provided in the text. Interestingly, the inhibitory effect exerted by A1 on the formation of DHT in GT1-1 cells can be mimicked by transforming growth factor beta 1 (TGF beta 1). Since TGF beta 1 had been previously shown to be directly involved in the stimulatory control of LHRH secretion by GT1-1 cells, acting both on LHRH release [R.C. Melcangi, M. Galbiati, E. Messi, F. Piva, L. Martini, M. Motta, Type 1 astrocytes influence luteinizing hormone-releasing hormone release from the hypothalamic cell line GT1-1: is transforming growth factor-beta the principle involved? Endocrinology 136 (1995) 679-686.] and gene expression [M. Galbiati, M. Zanisi, E. Messi, I. Cavarretta, L. Martini, R.C. Melcangi, Transforming growth factor-beta and astrocytic conditioned medium influence LHRH gene expression in the hypothalamic cell line GT1, Endocrinology 137 (1996) 5605-5609], the present data also show that TGF beta 1 might intervene in modulating feedback signals reaching hypothalamic LHRH producing neurons. The present findings underline once more the importance of the physiological crosstalk between A1 and neurons. (C) 1999 Elsevier Science Ltd, All rights reserved
The brain: a vulnerable target
No full textThis article addresses the description of several endocrine-related functions of the brain. It has emerged that steroids and growth factors may influence brain functions, and that brain cells may metabolize sex steroids. The crosstalk between different types of brain cells (neurons, astrocytes, the LHRH (luteinizing hormone-releasing hormone) producing GT1 cell line, etc.) has been described. Of relevance is that brain enzymes may convert sex steroids into compounds able to bind the GABAa receptor, creating a link between brain steroids and one neurotransmitter system. The data presented also provide the first demonstration that glial-neuronal interactions may intervene, in conjunction with neuronal-neuronal communications, in the control of the secretion of hypothalamic hormones. The detailed discussion of all these mechanisms has provided a long list of possible targets during the aging process. Fortunately, the demonstration that stem cells may be rescued in the "adult" CNS by the proper manipulations with growth factors opens new hope and directions for future interventions
Androgen metabolism in the brain
No full textThe paper summarizes the most recent views on androgen metabolism in the brain. In particular it will be shown that: (1) the enzyme 5 alpha-reductase is particularly concentrated in the white matter; (2) 5 alpha-reductase is also present in the myelin; 5 alpha-reductase is present in higher concentrations in neurons (isolated or cultured) that in glial cells (astrocytes and oligodendrocytes); (4) only neurons possess the capability of aromatizing androgens to estrogens; and (5) a possible role of steroid metabolism in the control of the process of myelinogenesis is suggested
Testosterone and progesterone metabolism in the human neuroblastoma cell line SH-SY5Y
No full textThe ability of the human neuroblastoma cell line SH-SY5Y to metabolize androgens and progesterone was studied by incubating the cells in the presence of labeled testosterone (T) or progesterone (P) to measure, respectively, the formation of dihydrotestosterone (DHT) or dihydroprogesterone (DHP) (5 alpha-reductase activity). The 3 alpha-hydroxysteroid dehydrogenase activity was studied by evaluating the conversion of labeled DHT into 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). The results show that undifferentiated neuroblastoma cells possess a significant 5 alpha-reductase activity, as shown by the considerable conversion of T into DHT; moreover, this enzymatic activity seems to be significantly stimulated following cell differentiation induced by the phorbol ester TPA, but not after differentiation induced by retinoic acid (RA). The 5 alpha-reductase(s) present in SH-SY5Y cells is also able to convert P into DHP. In undifferentiated cells, this conversion was about 8 times higher than that of T into DHT. Under the influences of TPA and RA, the formation of DHP followed the same pattern observed for the formation of DHT. SH-SY5Y cells also appear to possess the enzyme 3 alpha-hydroxysteroid dehydrogenase, since they are able to convert DHT into 3 alpha-diol. This enzymatic activity is not altered following TPA-induced differentiation and appears to be decreased following treatment with RA. It is suggested that the SH-SY5Y cell line may represent a useful "in vitro" model for the study of the mechanisms involved in the control of androgen and P metabolism in nervous cells
Androgen and progesterone metabolism in the central and peripheral nervous system
No full textThis paper summarizes the most recent data obtained in the authors' laboratory on the metabolism of testosterone and progesterone in neurons, in the glia, and in neuroblastoma cells. The activities of the 5 alpha-reductase (the enzyme that converts testosterone into dihydrotestosterone, DHT), and of the 3 alpha-hydroxysteroid dehydrogenase (the enzyme that converts DHT into 5 alpha-androstane-3 alpha, 17 beta-diol, 3 alpha-diol) have been first evaluated in primary cultures of neurons, oligodendrocytes and type-1 and -2 astrocytes, obtained from the fetal or neonatal rat brain. All the cultures were used on the fifth day. The formation of DHT of 3 alpha-diol was evaluated incubating the different cultures with labeled testosterone or DHT as substrates. The results obtained indicate that the formation of DHT takes place preferentially in neurons; however, type-2 astrocytes and oligodendrocytes also possess considerable 5 alpha-reductase activity, while type-1 astrocytes show a much lower enzymatic concentration. A completely different localization was observed for 3 alpha-hydroxysteroid dehydrogenase; the formation of 3 alpha-diol appears to be prevalently, if not exclusively, present in type-1 astrocytes; 3 alpha-diol is formed in very low yields by neurons, type-2 astrocytes and oligodendrocytes. The compartmentalization of two strictly correlated enzymes (5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase) in separate central nervous system (CNS) cell populations suggests the simultaneous participation of neurons and glial cells in the 5 alpha-reductive metabolism of testosterone. Subsequently it has been shown that, similarly to what happens when testosterone is used as the substrate, the 5 alpha-reductase which metabolizes progesterone into 5 alpha-pregnane-3,20-dione (DHP) shows a significantly higher activity in neurons than in glial cells; however, type-1 and -2 astrocytes as well as oligodendrocytes also possess some ability to 5 alpha-reduce progesterone. On the other hand, 3 alpha-hydroxysteroid dehydrogenase, the enzyme which converts DHP into 5 alpha-pregnane-3 alpha-ol-20-one, appears to be present mainly in type-1 astrocytes; much lower levels of this enzyme are present in neurons and in type-2 astrocytes. At variance with the previous results obtained using androgens as precursors, oligodendrocytes show considerable 3 alpha-hydroxysteroid dehydrogenase activity, even if this is statistically lower than that present in type-1 astrocytes. The existence of isoforms of the enzyme involved in androgen and progesterone metabolism is discussed.(ABSTRACT TRUNCATED AT 400 WORDS
Steroids and glial function
No full textHormonal and locally produced steroids act in the nervous
system as neuroendocrine regulators, as trophic factors and
as neuromodulators and have a major impact on neural development
and function. Glial cells play a prominent role in
the local production of steroids and in the mediation of steroid
effects on neurons and other glial cells. In this review,
we examine the role of glia in the synthesis and metabolism
of steroids and the functional implications of glial steroidogenesis.
We analyze the mechanisms of steroid signaling on
glia, including the role of nuclear receptors and the mechanisms
of membrane and cytoplasmic signaling mediated
by changes in intracellular calcium levels and activation of
signaling kinases. Effects of steroids on functional parameters
of glia, such as proliferation, myelin formation, metabolism,
cytoskeletal reorganization, and gliosis are also
reviewed, as well as the implications of steroid actions on
glia for the regulation of synaptic function and connectivity,
the regulation of neuroendocrine events, and the response
of neural tissue to injury
The 5 alpha-reductase in the brain: molecular aspects and relation to brain function
No full textAll the classes of hormonal steroids physiologically produced in the body (androgens, estrogens, progestagens, and corticosteroids) are able to exert important effects on the brain, but the mechanisms of their actions are not always well understood. Steroids may interact with intracellular receptors to activate the genome, but some of their effects are probably extragenomic and involve interactions with cellular membranes. Moreover, not all the steroids act always in their native molecular form; a large group of them must actually be transformed into "active" metabolites. This may occur at the level of their respective target structures. For example, androgens are metabolized in the brain into estrogens and into 5 alpha-reduced androgens, like 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone; DHT) and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). Progesterone, and possibly corticosteroids, may also be transformed into their corresponding 5 alpha-reduced metabolites. Also the cellular target (neurons and/or glial cells) of the hormonal steroids in the brain is not always clear. This review analyzes in detail one of the two major enzymatic systems that transform steroids in the brain, namely the 5 alpha-reductase-3 alpha-(3 beta)-hydroxysteroid dehydrogenase pathway. An active 5 alpha-reductase-3 alpha-hydroxysteroid dehydrogenase system is widely distributed in practically all CNS structures in all phases of development. In the brain, this enzymatic system is not regulated by castration or sex steroid administration; furthermore, neural inputs seem to be ineffective at the hypothalamic level. A recent interesting finding is the presence of high concentrations of the 5 alpha-reductase in the white matter. This probably is due to the fact that the white matter is particularly rich in myelin membranes, with which the enzymatic activity appears to be associated. An active 5 alpha-reductase activity has also been shown to be present in peripheral myelinated nerves. The localization in myelin membranes may suggest a possible involvement of 5 alpha-reduced metabolites of the different steroids in the process of myelination. The presence of the 5 alpha-reductase was analyzed in neurons, astrocytes, and oligodendrocytes isolated from the brains of male rats, as well as in neurons and glial cells grown in culture. Neurons appear to be more active than glial cells in converting testosterone into DHT. Only neurons possess aromatase activity.(ABSTRACT TRUNCATED AT 400 WORDS
Neuroprotective effects of neuroactive steroids in the spinal cord and peripheral nerves
No full text
Testosterone and progesterone metabolism in the central nervous system: cellular localization and mechanism of control of the enzymes involved
No full textThis paper summarizes the most recent data obtained in the authors' laboratory on the metabolism of testosterone and progesterone in neurons and in the glia. 1. The activities of 5 alpha-reductase (the enzyme that converts testosterone into dihydrotestosterone; DHT) and of 3 alpha-hydroxy steroid dehydrogenase (the enzyme that converts DHT into 5 alpha-androstane-3 alpha, 17 beta-diol; 3 alpha-diol) were first evaluated in primary cultures of neurons, oligodendrocytes, and type-1 and type-2 astrocytes, obtained from the fetal or neonatal rat brain. The formation of DHT and 3 alpha-diol was evaluated incubating the different cultures with labeled testosterone or labeled DHT as substrates. The results obtained indicate that the formation of DHT takes place preferentially in neurons; however, also type-2 astrocytes and oligodendrocytes possess considerable 5 alpha-reductase activity. A completely different localization was observed for 3 alpha-hydroxysteroid dehydrogenase; the formation of 3 alpha-diol appears to be prevalently, if not exclusively, present in type-1 astrocytes; 3 alpha-diol is formed in very low yields by neurons, type-2 astrocytes, and oligodendrocytes. Moreover, the results indicate that, in type 1 astrocytes, both 5 alpha-reductase and 3 alpha-HSD are stimulated by coculture with neurons and by the addition of neuron-conditioned medium, suggesting that secretory products released by neurons might intervene in the control of glial cell function. 2. Subsequently it was shown that, similarly to what happens when testosterone is used as the substrate, 5 alpha-reductase, which metabolizes progesterone into 5 alpha-pregnane-3,20-dione, (DHP), shows a significantly higher activity in neurons than in glial cells; however, also type-1 and type-2 astrocytes as well as oligodendrocytes possess some ability to 5 alpha-reduce progesterone. On the contrary, 3 alpha-hydroxysteroid dehydrogenase, the enzyme which converts DHP into 5 alpha-pregnane-3 alpha-ol-20-one (THP), appears to be present mainly in type-1 astrocytes; much lower levels of this enzyme are present in neurons and in type-2 astrocytes. At variance with the previous results obtained using androgens as precursors, oligodendrocytes show considerable 3 alpha-hydroxysteroid dehydrogenase activity, even if this is statistically lowe than that present in type-1 astrocytes. The existence of isoenzymatic forms of the enzymes involved in androgen and progesterone metabolism is discussed
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