Involvement of GLCCI1 in mouse spermatogenesis.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2023 Jan

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Spermatid production is a complex regulatory process in which coordination between hormonal control and apoptosis plays a pivotal role in maintaining a balanced number of sperm cells. Apoptosis in spermatogenesis is controlled by pro-apoptotic and anti-apoptotic molecules. Hormones involved in the apoptotic process during spermatogenesis include gonadotrophins, sex hormones, and glucocorticoid (GC). GC acts broadly as an apoptosis inducer by binding to its receptor (glucocorticoid receptor: GR) during organ development processes, such as spermatogenesis. However, the downstream pathway induced in GC-GR signaling and the apoptotic process during spermatogenesis remains poorly understood. We reported previously that GC induces full-length glucocorticoid-induced transcript 1 (GLCCI1-long), which functions as an anti-apoptotic mediator in thymic T cell development. Here, we demonstrate that mature murine testis expresses a novel isoform of GLCCI1 protein (GLCCI1-short) in addition to GLCCI1-long. We demonstrate that GLCCI1-long is expressed in spermatocytes along with GR. In contrast, GLCCI1-short is primarily expressed in spermatids where GR is absent; instead, the estrogen receptor is expressed. GLCCI1-short also binds to LC8, which is a known mediator of the anti-apoptotic effect of GLCCI1-long. A luciferase reporter assay revealed that β-estradiol treatment synergistically increased Glcci1-short promotor-driven luciferase activity in Erα-overexpressing cells. Together with the evidence that the conversion of testosterone to estrogen is preceded by aromatase expression in spermatids, we hypothesize that estrogen induces GLCCI1-short, which, in turn, may function as a novel anti-apoptotic mediator in mature murine testis. © 2022 Federation of American Societies for Experimental Biology.

Citation

Masaru Takada, Daisuke Fukuhara, Toshihiko Takiura, Yukino Nishibori, Masashi Kotani, Zentaro Kiuchi, Akihiko Kudo, Olga Beltcheva, Noriko Ito-Nitta, Kazuhiro R Nitta, Toru Kimura, Jun-Ichi Suehiro, Tomohisa Katada, Hiromu Takematsu, Kunimasa Yan. Involvement of GLCCI1 in mouse spermatogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2023 Jan;37(1):e22680