Oligodendrocyte Progenitor Proliferation and Maturation Is Differentially Regulated by Male and Female Sex Steroid Hormones

Marin-Husstege, Mireya; Muggironi, Michela; Raban, D.; Skoff, Robert P.; Casaccia‐Bonnefil, Patrizia

doi:10.1159/000082141

Cited by 110 publications

(104 citation statements)

References 61 publications

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“…Some differences in estrogen-induced kinase activity between female and male OLs were observed (Fig. 5), and could be due to differences in ratios of different mER receptors, a modulating effect of androgen receptors, or an effect of the original in vivo environment of the OLs on their developmental potential (Marin-Husstege et al, 2004). However, the fact that both female and male OLs have mERa/b, which mediates nongenomic signaling pathways via 17a and 17b-estradiol and PPT and DPN, suggests that both female and male OLs have similar potential to respond to non-genomic estrogen stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…However, the function of these extranuclear receptors in OLs is not known. Prolonged exposure to estradiol stimulates proliferation and differentiation of OLs (Jung-Testas et al, 1992;Marin-Husstege et al, 2004;Zhang et al, 2004), and protects them from cell death because of hyperoxia or cytotoxic agents (Gerstner et al, 2007;Takao et al, 2004), but these effects may have been mediated through the nuclear receptor. To provide evidence for a role for a membrane ER in rapid signaling in OLs, we have investigated the effect of both 17a-and 17b-estradiol on short-term activation of several signaling pathways known to be involved in development of myelinating cells, involving MAPK, Akt, and GSK-3b (Cui et al, 2005;Khorchid et al, 1999;Ogata et al, 2004;Palacios et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Hirahara

Matsuda

Gao

et al. 2008

Glia

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There is general acceptance that the estrogen receptor can act as a transcription factor. However, estrogens can also bind to receptors that are located at the plasma membrane and stimulate rapid intracellular signaling processes. We recently showed that a membrane-associated estrogen receptor (mER) is present within myelin and at the oligodendrocyte (OL) plasma membrane. To understand the physiological function of mER in OLs, we investigated its cellular localization and involvement in rapid signaling in CG4 cells and OL primary cultures. An ERa was expressed along the lacy network of veins in the membrane sheets and in the perikaryon and nucleus in OLs. ERb was located in the nucleus, and to a lesser extent along the veins. The expression of ERa and ERb in OL membranes was confirmed by Western analysis of isolated membranes. OL membranes mainly had truncated forms of ERa, 53 and 50 kDa, in addition to some 65 kDa form, whereas ERb was a 54 kDa form. CG4 cells and OLs were pulsed with 17a-and 17b-estradiol for various times and the total lysates were analyzed for phosphorylated kinases. Both 17a-and 17b-estradiol elicited rapid phosphorylation of p42/44MAPK, Akt, and GSK-3b within 8 min. This rapid signaling is consistent with estradiol ligation of a membrane form of ER. Since 17a-estradiol is produced at higher concentrations than 17b-estradiol in the brain of both sexes, signaling via 17a-estradiol-liganded mER may have an important function in OLs. V V C

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Hirahara

Matsuda

Gao

et al. 2008

Glia

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“…In contrast to the intrinsic synthesis of progesterone by Olgs, they do not express enzymes necessary for synthesis of estradiol or testosterone (Zwain and Yen, 1999). However, Olgs express these receptors (Jung-Testas et al, 1994;Finley and Kritzer, 1999;Zhang et al, 2004), and, in tissue culture, the proliferation, maturation, and death of Olgs varies depending on concentrations of estrogen (Marin-Husstege et al, 2004;Takao et al, 2004). Estrogen appears to enhance survival of cultured, mature Olgs when exposed to cytotoxic compounds (Takao et al, 2004).…”

Section: Oligodendrocyte Proliferation and Cell Death Is Increased Inmentioning

confidence: 99%

Proliferation and Death of Oligodendrocytes and Myelin Proteins Are Differentially Regulated in Male and Female Rodents

et al. 2006

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Sexual dimorphism of neurons and astrocytes has been demonstrated in different centers of the brain, but sexual dimorphism of oligodendrocytes and myelin has not been examined. We show, using immunocytochemistry and in situ hybridization, that the density of oligodendrocytes in corpus callosum, fornix, and spinal cord is 20 -40% greater in males compared with females. These differences are present in young and aged rodents and are independent of strain and species. Proteolipid protein and carbonic anhydrase-II transcripts, measured by real-time PCR, are approximately two to three times greater in males. Myelin basic protein and 2Ј,3Ј-cyclic nucleotide 3Ј-phosphodiesterase, measured by Western blots, are 20 -160% greater in males compared with females. Surprisingly, both generation of new glia and apoptosis of glia, including oligodendrocytes, are approximately two times greater in female corpus callosum. These results indicate that the lifespan of oligodendrocytes is shorter in females than in males. Castration of males produces a female phenotype characterized by fewer oligodendrocytes and increased generation of new glia. These findings indicate that exogenous androgens differentially affect the lifespan of male and female oligodendrocytes, and they can override the endogenous production of neurosteroids. The data imply that turnover of myelin is greater in females than in males. -Calpain, a protease upregulated in degeneration of myelin, is dramatically increased at both transcriptional and translational levels in females compared with males. These morphological, molecular, and biochemical data show surprisingly large differences in turnover of oligodendrocytes and myelin between sexes. We discuss the potential significance of these differences to multiple sclerosis, a sexually dimorphic disease, whose progression is altered by exogenous hormones.

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“…This suggests that the lifespan of oligodendrocytes in females is reduced, which could limit the number of axons that become myelinated. In vitro, estrogen delays the exit of oligodendrocytes from the cell cycle which results in higher numbers of proliferating oligodendrocytes in cell cultures derived from female tissue (Marin-Husstege et al, 2004). However, the possible role of ovarian hormones on the sex differences in oligodendrocyte survival in vivo remains unexplored.…”

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confidence: 99%

Pubertal ovarian hormone exposure reduces the number of myelinated axons in the splenium of the rat corpus callosum

Yates

Juraska

2008

Experimental Neurology

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The size of the female rat corpus callosum decreases in response to pubertal ovarian hormone exposure, but the underlying changes in axonal composition have not been examined. In the current study, animals underwent ovariectomy or sham surgery at day 20, and the number of myelinated and unmyelinated axons were examined in young adulthood (2 mo.) using electron microscopy. Ovariectomized animals had a greater number of myelinated axons compared to intact animals, while total axon number was not affected. Ovarian hormone exposure seems to limit the number of axons that become myelinated in the splenium, while not affecting the number of axons crossing through the region. Keywordsestrogen; progesterone; myelin; oligdodendrocyte; adolescence; corticosteroids The corpus callosum is sexually dimorphic in the rat, with males having a larger total corpus callosum size than females (Berrebi et al, 1988;Fitch et al, 1991;Bimonte et al., 2000a;2000b;2000c;Denenberg et al., 1991). The splenium, defined as the posterior 20% of the total callosal length, carries axons from the visual cortex (Kim et al., 1996). Sex differences in the size of the splenium (Nunez and Juraska, 1998) are due to a greater number of myelinated axons within the splenium of males though there are no differences in total axon number (Kim et al., 1996). Differences in myelinated axon number are established by young adulthood (day 60), but are not seen in prepubertal animals examined at 25 days of age (Kim and Juraska, 1997). On the other hand, females have more total axons at day 25. However, because of continued axon elimination in females this difference is abolished by day 60 (Kim and Juraska, 1997). Thus, the onset of puberty around day 35 may affect both myelination and axon withdrawal.Prepubertal ovariectomy (OVX) at day 25 has been shown to increase the overall size of the corpus callosum in adulthood (Bimonte et al., 2000a(Bimonte et al., , 2000b(Bimonte et al., , 2000c, while OVX at day 70 is without effect (Bimonte et al, 2000c). The underlying structural changes responsible for this increase in size have not been examined. It is possible that the removal of ovarian hormones before puberty reduces axon elimination or increases the number of axons that get myelinated, resulting in a greater callosal size. In the primary visual cortex, which projects axons through Corresponding author: Janice M. Juraska, Ph.D., Department of Psychology, 603 E. Daniel St., Champaign, IL 61820, (217) 333-8546, Fax: (217) 244-5876, jjuraska@cyrus.psych.uiuc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Pu...

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Oligodendrocyte Progenitor Proliferation and Maturation Is Differentially Regulated by Male and Female Sex Steroid Hormones

Cited by 110 publications

References 61 publications

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

The localization and non‐genomic function of the membrane‐associated estrogen receptor in oligodendrocytes

Proliferation and Death of Oligodendrocytes and Myelin Proteins Are Differentially Regulated in Male and Female Rodents

Pubertal ovarian hormone exposure reduces the number of myelinated axons in the splenium of the rat corpus callosum

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