Follicle-stimulating hormone and leukemia inhibitory factor regulate sertoli cell retinol metabolism

Sertoli cells, the somatic epithelial cells of the seminiferous tubules, pr ovide both structural and biochemical support for developing male germ cell s. The Sertoli cells are targets of retinoid action in the testis. We have found that FSH, (Bu)(2)cAMP, and leukemia inhibitory factor elicit substant ial changes in the metabolism of [H-3]retinol (vitamin A) in primary cultur es of purified rat Sertoli cells. Addition of (Bu)(2)cAMP for 2 h or FSH fo r 6 h results in a 3-fold increase in the metabolism of [H-3]retinol to [H- 3]retinoic acid ([H-3]RA); the esterification of [H-3]retinol to [H-3]retin yl esters, especially [H-3]retinyl palmitate, is also increased by approxim ately 5-fold. The addition of 1 muM all-trans-RA also elicits changes in [H -3] retinol metabolism, but in this case the metabolism of [H-3]retinol to [H-3]RA is inhibited, whereas the metabolism of [H-3]retinol to [H-3]retiny l esters is increased by over 50-fold. Leukemia inhibitory factor increases the esterification of [H-3]retinol by 2- to 3-fold. FSH leads to a reducti on in the level of cellular retinol binding protein I transcripts, whereas RA increases the cellular retinol binding protein I messenger RNA level by about 2-fold at approximately 24 h. Levels of AHD-2 (aldehyde dehydrogenase -2) and RALDH-2 (retinaldehyde dehydrogenase-2) messenger RNAs, which encod e enzymes that convert [H-3]retinaldehyde to [H-3]RA, are increased by abou t 2-fold by FSH, whereas no change in CYP26 (RA hydroxylase) expression is seen. Our results suggest that one function of FSH (and/or (Bu)(2)cAMP) in Sertoli cells is to increase the metabolism of retinol to the biologically active metabolite RA and to retinyl esters.