17Beta-Estradiol Induces the Translocation of the Estrogen Receptors ESR1 and ESR2 to the Cell Membrane, MAPK3/1 Phosphorylation and Proliferation of Cultured Immature Rat Sertoli Cells1

Abstract

The aim of the present study was to determine the mechanisms involved in estrogen actions in cultured rat Sertoli cells. RT-PCR detected transcripts for the estrogen receptors ESR1 and ESR2 in cultured immature Sertoli cells and in the testis of 15-, 28-, and 120-day-old rats. The expression of ESR1 and ESR2 was confirmed in Sertoli cells by immunofluorescence and Western blot. Immunohistochemistry with cryosections of testes from immature and adult rats revealed that ESR1 is present in Sertoli, Leydig, and some peritubular myoid cells, and ESR2 is present in multiple cell types, including germ cells. Treatment of Sertoli cells with 17beta-estradiol (E(2)) induced a translocation of ESR1 and ESR2 to the plasma membrane and a concomitant phosphorylation of MAPK3/1. Both effects reached a maximum after 10 min and were blocked by PP2, an inhibitor of the SRC family of protein tyrosine kinases, and by the antiestrogen ICI 182,780 (ICI). MAPK3/1 phosphorylation was also decreased in the presence of AG 1478, an inhibitor of the epidermal growth factor receptor (EGFR) kinase, and in the presence of MAP2K1/2 inhibitor UO126. Treatment with E(2) for 24 h increased the incorporation of [methyl-(3)H]thymidine, which was blocked by ICI. These results indicate that E(2) activates an SRC-mediated translocation of estrogen receptors to the plasma membrane, which results in the activation of EGFR and the mitogen-activated protein kinase signaling pathway. In addition, activation of ESR1 and/or ESR2 by E(2) is involved in proliferation of immature Sertoli cells. The estrogen actions in Sertoli cells might be a key step mediating cellular events important for spermatogenesis and fertility.

Administration of testosterone inhibits initiation of seminal tubule growth and decreases Sertoli cell number in the earliest period of rat's postnatal development.

“…Estradiol may contribute indirectly to the proliferation and maturation of Sertoli cell via the stimulation of FSH secretion, and is also likely to have direct paracrine actions within the testis augmenting the action of FSH on Sertoli cell function as shown previously [4,7]. It has been demonstrated recently that physiological levels of estrogen promotes proliferation of cultured immature rat SC [34]. Though, estrogens are usually recognized as factor inducing detrimental effects on SC number and function, it is suggested that this effect may depend on the blood concentration of the hormone [35,36].…”

Estrogen receptors and function in the male reproductive system

“…In testis from immature and adult rats, splicing variants for Esr1 were not detected, and only a single protein band for ESR1 was detected (20). On the other hand, two splicing variants were detected for Esr2 in testis: the Esr2_v1 isoform (20), with high similarity with the human ESR2 (21), and the Esr2_v2, which contains an in-frame insert of 54 nucleotides, only described in tissues from rodents (13).…”

“…On the other hand, two splicing variants were detected for Esr2 in testis: the Esr2_v1 isoform (20), with high similarity with the human ESR2 (21), and the Esr2_v2, which contains an in-frame insert of 54 nucleotides, only described in tissues from rodents (13). Esr2_v2 encodes a protein that differs from the isoform 1 of ESR2 only by an insertion of 18 aminoacids in the ligand binding domain.…”

“…Esr2_v2 encodes a protein that differs from the isoform 1 of ESR2 only by an insertion of 18 aminoacids in the ligand binding domain. In fact, in Western blot analysis only one protein band was distinguished with an antibody that recognizes the aminoterminal region of the receptor that is common to both ESR2 isoforms (20). The physiological implication of the existence of several ESR2 isoforms has been investigated.…”

The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1

“…In the testis of adult mice, both ER types have been identified: ERa is localized in Leydig cells, whereas ERb is expressed in Sertoli cells and most germ cells [3]. Although ERa has also been detected in rat Sertoli cells [4], no clear evidence documented its presence in the same cells of mice.…”