Et. Samy et al., Sertoli cell prostaglandin D-2 synthetase is a multifunctional molecule: Its expression and regulation, ENDOCRINOL, 141(2), 2000, pp. 710-721
PGD(2) synthetase (PGD-S; PGH(2) D-isomerase; EC 5.3.99.2) is a bifunctiona
l protein first identified in the mammalian brain. It acts as a PGD(2)-prod
ucing enzyme and a retinoid transporter. PGD-S is present in the testis, wh
ere its protein and messenger RNA levels are similar to those in the brain.
In view of its diversified regulatory functions, we investigated its regul
ation using primary cultures of Sertoli cells in vitro to assess its role i
n the testis. When Sertoli cells were cultured in serum-free medium to allo
w the formation of specialized junctions, it was found that PGD-S expressio
n increased steadily with time, coinciding with the formation of inter-Sert
oli junctions in vitro. However, neither germ cells (using a Sertoli/germ c
ell ratio between 1:1 and 1:30 when Sertoli cells were cultured at a densit
y of 5 x 10(4) cells/cm(2)) nor germ cell-conditioned medium affected the e
xpression of Sertoli cell PGD-S in vitro. These results thus unequivocally
demonstrated that germ cells do not play a role in regulating testicular PG
D-S expression. Although FSH, dihydrotestosterone, and testosterone had no
apparent effect on Sertoli cell PGD-S expression, the addition, of progeste
rone ( 1 x 10(-11) to 1 x 10(-9) M) and T-3 (1 x 10(-11) to 1 x 10(-9) M) t
o Sertoli cell cultures elicited a significant increase in PCD-S expression
by as much as 4.5- and 2.5 fold, respectively. As PGD-S is a known retinoi
d transporter, the effects of all-trans-retinoic acid and all-trans-retinal
on Sertoli cell PGD-S expression were also assessed. Both compounds were f
ound to induce Sertoli cell PGD-S expression. In summary, PGD-S is a putati
ve Sertoli cell product whose expression is regulated by progesterone, meta
bolites of vitamin A, and T-3. In view of its dual biological properties, a
study of its regulation and physiology will yield new insights into unders
tanding its role in the testis.