17β-Estradiol Regulates Cultured Immature Boar Sertoli Cell Proliferation via the cAMP-ERK1/2 Pathway and the Estrogen Receptor β

Estrogen plays an important role in regulating Sertoli cell number in the testis. The objective of the study was to identify whether 17 beta-estradiol affected the proliferation of cultured, immature boar Sertoli cells via the estrogen receptor beta (ER beta) and the cAMP-extracellular signal-regulated kinase (ERK1/2) pathway. Low levels (10(-10)-10(-8) mol L(-1)) of 17 beta-estradiol increased cell number, but high levels (10(-7)-10(-6) mol L(-1)) decreased it (P < 0.05). Sertoli cell number began to recover for an additional 24 h in the medium without 17 beta-estradiol (10(-6)mol L(-1)) (P>0.05). The effects of 17 beta-estradiol (10(-9) mol L(-1)) peaked at the first 24 h (P < 0.05). 17 beta-estradiol activated ERK1/2 from 5 min to 24 h, but the activiy of ERK1/2 began to decrease after 4 h. Both PD98059 and U0126, two ERK inhibitors, blocked cell division (P < 0.05). 17 beta-estradiol (10(-10)-10(-6) mol L(-1)) dose-dependently increased cAMP production (P<0.05), and both 17 beta-estradiol (10(-9) mol L(-1)) and forskolin, which increases cAMP levels, induced cell proliferation and activated ERK1/2 (P < 0.05). Rp-cAMP, an antagonist of cAMP, blocked this 17 beta-estradiol activity (P < 0.05). Two estrogen receptor antagonists, ICI 182780 and ER beta antagonist (ER beta Ant), reduced Sertoli cell number, cAMP production and ERK1/2 activation (P < 0.05), but ER alpha Ant did not (P> 0.05). Therefore, 17 beta-estradiol mainly promotes pig Sertoli cell proliferation via ER beta to induce cAMP production and ER beta activation to promote cell proliferation.