Mp. Hardy et al., LEYDIG-CELLS INCREASE THEIR NUMBERS BUT DECLINE IN STEROIDOGENIC FUNCTION IN THE ADULT-RAT AFTER NEONATAL-HYPOTHYROIDISM, Endocrinology, 132(6), 1993, pp. 2417-2420
Administration of the goitrogen, 6-propyl-2-thiouracil (PTU), to suckl
ing rat pups from birth through day 24 postpartum as a 0.1% solution i
n the mother's drinking water increases adult testis size and sperm pr
oduction by about 80% and 140%, respectively, without affecting periph
eral testosterone levels. The objectives of this study were to determi
ne whether adult Leydig cell numbers were altered in PTU-treated rats
and whether the steroidogenic function of these cells was normal. The
number of Leydig cells per testis at 180 days increased by 69% in PTU-
treated compared to control rats, whereas the average Leydig cell volu
me declined by about 20%. Steroidogenic function assessed in isolated
adult Leydig cells decreased after neonatal PTU treatment. LH-stimulat
ed testosterone production was reduced by 55% in Leydig cells from tre
ated rats, commensurate with a 50% decline in the number of hCG-bindin
g sites in these cells. The difference in steroidogenic potential was
even more striking after incubations with saturating concentrations of
steroid substrate, 22(R)-hydroxycholesterol; Leydig cells from treate
d males produced 73% less testosterone than controls. Therefore, this
decrease in testosterone production may be partially due to a reductio
n in the numbers of LH receptors, but also reflects the impaired stero
idogenic potential of these cells. These results clearly show that the
dramatic increase in adult Leydig cell number after neonatal PTU trea
tment is counterbalanced by a permanent decline in Leydig cell steroid
ogenic function, producing no net change in peripheral testosterone le
vels.