Prepuberal - Onset Hypothyroidism Induces Reversible Boost in Lipogenic Activity in Sertoli Cells of Adult Rats

Abstract

Sertoli cells, the major site of intermediary metabolism in the testis, are the target for thyroid hormone action, though thyroid hormone receptors are present in Leydig cells also. We have earlier shown specific changes in basal and LH-induced steroidogenic activity in Leydig cells of adult rats with transient prepuberal - onset hypothyroidism. In this paper we report the response of Sertoli cell lipids and lipogenic enzymes in adult rats to prepuberal onset hypothyroidism. Hypothyroidism was induced in 30 day old rats by surgical thyroidectomy. After 60 days, one group of hypothyroid rats was allowed to attain euthyroidism by L-thyroxine (T₄) replacement therapy (intramuscular injection of 6μg T₄/100 g body weight for thirty days) and sacrificed. Sertoli cells were isolated by enzymatic dispersion and the concentration of various lipid fractions and the activities of lipogenic enzymes were assessed. Hypothyroidism increased Sertoli cell total lipids and total cholesterol, glycereides and phospholipids. Of the lipogenic enzymes, activities of glucose-6-phosphate dehydrogenase, 6-phospho gluconate dehydrogenase and malic enzyme decreased, whereas those of NADP+ isocitrate dehydrogenase, ATP-citrate lyase, fatty acid synthase and α - glycerophosphate dehydrogenase increased. T₄ replacement to thyroidectomized rats maintained normal levels of most of the parameters. The present study indicates that thyroid hormones have an inhibitory effect on Sertoli cell lipogenesis. It is suggested that accumulation of lipids in Sertoli cells may be one of the biochemical mechanisms underlying prepuberal-onset hypothyroidism-induced male infertility, which can be corrected with timely treatment of T₄ to maintain euthyroidism.