Differential response of luteinizing hormone receptor and steroidogenic enzyme gene expression to human chorionic gonadotropin stimulation in the neonatal and adult rat testis.

To study further the functional differences of the fetal-neonatal and adult growth phases of Leydig cells, neonatal (5-day-old) and adult (60-day-old) male rats were challenged with a 600 IU/kg injection of human CG (hCG). Certain Leydig cell responses were monitored 1, 2, and 3 days after the hCG injection. The down-regulation of LH receptors and blockage of the 17-hydroxylase/C17-20 lyase step in adult testis, and the absence of these responses in neonatal testis were confirmed. Novel data were obtained on concomitant responses of LH receptor and steroidogenic enzyme messenger RNAs (mRNAs). The LH receptor mRNA was increased 4-5-fold by 2 days after hCG injection in the neonatal testis (P less than 0.05), but in the adult was decreased during all 3 days by 50% (P less than 0.05). The mRNA level of the cytochrome P450 for cholesterol side chain cleavage responded similarly at both ages, with a 180-260% increase during 2 and 3 days (P less than 0.05-0.01). In contrast, the 17-hydroxylase/17,20-lyase cytochrome P450 mRNAs displayed opposite responses, increasing 4.5-fold in 2 days (P less than 0.01) in the neonates, but decreasing by 80% in 1 day in the adults (P less than 0.01). No response of the aromatase cytochrome P450 mRNA to hCG stimulation was found at either age studied. These results demonstrate that the functional differences of the neonatal and adult Leydig cells to high gonadotropic stimulation occur at the level of expression of specific genes, including those of the LH receptor and the 17-hydroxylase/17,20-lyase cytochrome P450. Although aromatization of testicular androgens has been suggested to mediate the blockade of the 17-hydroxylase/C17-20 lyase step in adult testes, altered steady state levels of aromatase mRNA are not involved in this response. LH receptor mRNA decreases in adult rat testis in response to treatment with high levels of hCG. Thus, this phenomenon of down-regulation of membrane receptors includes a decreased LH receptor mRNA as well as cellular internalization of the existing receptors.