Are testicular cortisol and WISP2 involved in estrogen-regulated Sertoli cell proliferation?

Abstract

The number of Sertoli cells has a major effect on adult testis size and sperm production capacity. Mechanisms that regulate the number of Sertoli cells in livestock are at best nebulously understood; however, with lesser testicular estrogen production, proliferation of Sertoli cells is prolonged compared with vehicle-treated littermates. Decreased WISP2 gene expression in testes as a result of less endogenous estrogen is similar to altered WISP2 gene expression following corticosteroid treatment of some cultured cells. Taken together, these findings indicate decreased testicular cortisol might be in the signaling pathway between reduced endogenous estrogens and the prolonged interval of Sertoli cell proliferation. Hence, in these studies, potential actions of testicular corticosteroid on Sertoli cell numbers were evaluated. Testicular cortisol concentrations were reduced at 6.5 weeks of age (P < 0.05) in littermates treated with the aromatase inhibitor, letrozole, compared with littermates treated with vehicle. Letrozole treatment leads to reduced testicular estradiol and greater Sertoli cell numbers during the early juvenile interval in pigs. The inverse relationship between testicular glucocorticoid and Sertoli cell proliferation was also tested by increasing local testicular glucocorticoids using the synthetic compound, dexamethasone. Local administration beginning at 1.5 weeks of age (osmotic pump and catheter (n = 3) or a silastic implant (n = 5)) reduced Sertoli cell numbers at 6.5 weeks of age compared with littermates that received the vehicle treatment (P< 0.05). In summary, testicular glucocorticoid concentration was inversely correlated with Sertoli cell numbers during the first wave of Sertoli cell proliferation.