Corticosteroid 11β-Dehydrogenase in Rat Testis*

Abstract

Corticosteroid 11 beta-dehydrogenase, the enzyme that catalyzes the oxidation of the biologically active steroid cortisol to its inactive metabolite cortisone, is present in testis. Since excess cortisol in men and other mammals and excess corticosterone in rodents cause physiological abnormalities including abnormal testicular function, it was pertinent to study the cellular distribution of 11 beta-dehydrogenase in the testis. Purified antiserum directed against homogeneous rat 11 beta-dehydrogenase was used to localize the enzyme in the developing rat testis. With immunofluorescence, the enzyme was not detectable in fetal testis or in the testis of young male rats until the 26th day of development. A few interstitial cells were stained in the testis of 26-day-old animals. In the testis of 31-day-old rats many cells in the interstitium were positive. In adult animals the entire interstitial region displayed bright fluorescence. Depleting animals of germ cells did not abolish the fluorescence. The appearance of this enzyme correlates temporally with the postnatal increase in Leydig cell number and the developmental rise in serum testosterone. We suggest that 11 beta-dehydrogenase of Leydig cells protects the testis from the deleterious effects of cortisol.

Comparison of cell types in the rat Leydig cell lineage after ethane dimethanesulfonate treatment

“…2B). These data indicate that 21 days post-EDS, cells in the Leydig cell lineage were mostly RPLCs as most 3bHSD1-positive cells regenerated at this time were not stained with 11bHSD1, a biomarker for immature Leydig cells during puberty (Phillips et al 1989).…”

“…SRD5A1 disappears in Leydig cells when immature Leydig cells differentiate into ALCs, leading to testosterone becoming the primary androgen (Ge & Hardy 1998). Interestingly, a glucocorticoid-metabolizing enzyme, 11b-hydroxysteroid dehydrogenase 1 (11bHSD1, encoded by Hsd11b1), starts its expression in immature Leydig cells of rat testis at postnatal day 28 (Phillips et al 1989, Neumann et al 1993, Ge et al 1997. 11bHSD1 is a biomarker for Leydig cell development in adult population and plays a role in the regulation of testosterone production .…”

Rapid mechanisms of glucocorticoid signaling in the Leydig cell☆

“…Enzyme histochemistry detects the oxidative component of oxidoreductases, with electron transfer to the enzyme's pyridine cofactor forming NADPH and further electron donation to diaphorase (a ubiquitouslyexpressed enzyme), and finally to the tetrazolium salt dye, resulting in deposition of blue formazan crystals [40]. When an antibody to 11βHSD1 was produced [41], immunocytochemical staining revealed abundant expression of type 1 protein in rat Leydig cells postnatally [42]. The protein is not present in the fetal Leydig cells that develop in the testis prior to birth, and expressed only weakly in the postnatal generation of Leydig cells until mid-puberty (day 31 postpartum) [42,43].…”

“…When an antibody to 11βHSD1 was produced [41], immunocytochemical staining revealed abundant expression of type 1 protein in rat Leydig cells postnatally [42]. The protein is not present in the fetal Leydig cells that develop in the testis prior to birth, and expressed only weakly in the postnatal generation of Leydig cells until mid-puberty (day 31 postpartum) [42,43]. Based on an apparent association between the postnatal increases in testicular 11βHSD1 expression and pubertal maturation of testosterone secretion, oxidative inactivation of glucocorticoids by 11βHSD1 within the testis alleviating GR-mediated suppression of androgen biosynthesis in adult rat Leydig cells has been proposed [44].…”

Cloning and Primary Structure of Murine 11β‐Hydroxysteroid Dehydrogenase/Microsomal Carbonyl Reductase

“…A defined role for 1lP-HSDlA as modulator of glucocorticoid hormone action in cell lines containing the type-I1 receptor was shown (Stewart and Whorwood, 1994;Duperrex et al, 1993). The 11P-HSDIA isoform also plays a fundamental role in glucocorticoid-dependent androgen secretion of Leydig cells or could mediate cortisoldependent regulation of vascular tone in resistance vessels (Philipps et al, 1989;Monder et al, 1994;Walker and Moisan, 1992).…”