Histone deacetylase inhibitors suppress transdifferentiation of gonadotrophs to prolactin cells and proliferation of prolactin cells induced by diethylstilbestrol in male mouse pituitary

  • Nandar Tun
  • Yasuaki Shibata
  • Myat Thu Soe
  • Myo Win Htun
  • Takehiko KojiEmail author
Original Paper


Diethylstilbestrol (DES), an estrogen agonist, increases prolactin (PRL) cells through transdifferentiation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells to PRL cells as well as proliferation of PRL cells in adult male mouse pituitary. Since hyperacetylation of histone H3 is implicated in the regulation of activation of various genes, we examined the effect of DES on the state of histone H3 acetylation. DES significantly reduced the immunohistochemical signal for acetylated histone H3 at lysine 9 (H3K9ac) in PRL, LH and FSH cells, but not for H3K18ac or H3K23ac. DES-treated mice were injected intraperitoneally with HDAC inhibitors (HDACi), sodium phenylbutyrate (NaPB) or valproic acid (VPA), to mimic the acetylation level of histone H3. As expected, HDACi treatment restored the level of H3K9ac expression in these cells, and also inhibited DES-induced increase in PRL cells. Furthermore, NaPB and VPA also abrogated the effects of DES on the population density of both LH and FSH cells. Similarly, the numbers of proliferating and apoptotic cells in the pituitary in NaPB- or VPA-treated mice were comparable to those of the control mice. Considered together, these results indicated that the acetylation level of histone H3 plays an important role in DES-induced transdifferentiation of LH to PRL cells as well as proliferation of PRL cells.


Diethylstilbestrol Prolactin Gonadotrophs Transdifferentiation Histone H3 lysine 9 acetylation Histone deacetylase inhibitor 



This work was supported by the Grant-in-Aid for Scientific Research from Japanese Ministry of Education, Culture, Sports, Science and Technology (nos. 1247003, 15390058, 16659047, 16H05813 and 16K15173 to T. Koji) and by a grant from the Japanese Environment Agency (to T. Koji). We thank Dr. Daisuke Endo and Mrs. Shiho Kondo for their helpful advice and technical support.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Nandar Tun
    • 1
  • Yasuaki Shibata
    • 1
  • Myat Thu Soe
    • 1
  • Myo Win Htun
    • 1
  • Takehiko Koji
    • 1
    Email author
  1. 1.Department of Histology and Cell BiologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan

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