The Sertoli cells play an essential role in the maintenance and control of spermatogenesis. The ecto-
nucleoside triphosphate diphosphohydrolase (E-NTPDase) and
5'-nucleotidase activities can modulate the extracellular
adenine nucleotide levels, controlling
nucleotide-mediated signaling events in Sertoli cells. Since
thyroid hormones (TH) and
adenine nucleotides and
nucleosides play important modulatory roles in Sertoli cell proliferation and differentiation, the aim of our study was to investigate the effect of
hypothyroidism upon the NTPDase and
5'-nucleotidase activities in Sertoli cell cultures, as well as to verify whether these effects may be reversed by short and long-term supplementation with TH.
Congenital hypothyroidism was induced by adding 0.02%
methimazole in the
drinking water from day 9 of gestation and continually until 18 days of age.
Hypothyroidism significantly decreased the extracellular
ATP and
ADP hydrolysis and this effect was significantly reversed when cell cultures were supplemented with 1 microM T3 or 0.1 microM T4 for 30 min. In contrast,
AMP hydrolysis was not altered by
hypothyroidism, but was increased by T4 supplementation for 24 h. The presence of the
enzymes NTPDase 1, 2 and 3 was detected by RT-PCR in Sertoli cell cultures, however,
hypothyroidism was not able to alter the expression of these
enzymes. These findings demonstrate that TH modify NTPDase activities in hypothyroid Sertoli cells, probably via nongenomic mechanisms and, consequently, may influence the reproductive function throughout development.