Thyroid Hormone Effects on Sertoli Cell Gene Expression in the Rat

79 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1998.Thyroid hormones, along with other hormones such as follicle stimulating hormone (FSH), regulate neonatal Sertoli cell development. It was not clear however, if all of the changes seen in Sertoli cell development during hypothyroidism represent direct effects of thyroid hormone deficiency on the Sertoli cells, or if some effects result from secondary changes due to hypothyroidism. The aim of the present studies was to determine if the effects of hypothyroidism on Sertoli cell development are mediated in part by autocrine changes in hormone production and receptor expression and/or by changes in systemic hormones that could affect Sertoli cell activity. Three specific hypotheses were tested: (1) TSH regulates inhibin-$\alpha$ mRNA expression in cultured neonatal rat Sertoli cells; (2) expression of AR mRNA is regulated by T$\sb3$ in developing rat Sertoli cells in vitro and (3) expression of MIS mRNA is regulated by T$\sb3$ in neonatal rat Sertoli cells. Sertoli cells were enzymatically isolated from 2, 5- and 20-day-old rat testes and were grown in serum free medium with or without hormone treatment. At the end of the culture period total RNA was extracted from these cultures to perform Northern blot analysis. The major findings were: (1) TSH does not regulate inhibin-$\alpha$ production in cultured Sertoli cells. (2) T$\sb3$ stimulates AR mRNA expression in cultured Sertoli cells and (3) MIS mRNA expression in neonatal Sertoli cells is down-regulated by T$\sb3.$ Collectively, these results indicate that in addition to its direct effects on Sertoli cell protein production, T$\sb3$ also induces changes AR mRNA expression, which could increase androgen sensitivity and be a key element in normal Sertoli cell maturation. In addition, T$\sb3$ is a major regulator of MIS mRNA expression and many effects of T$\sb3$ may also partially reflect changes in MIS action. The present data provide a more complete understanding of the gamut of T$\sb3$ actions on the developing Sertoli cell and indicate that T$\sb3$ is one of the major regulators of Sertoli cell function.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD