Fetal development of Leydig cell activity in the mouse is independent of pituitary gonadotroph function.

During fetal development the testes secrete anti-Mullerian hormone and testosterone to induce formation of the male phenotype. Adult Leydig cells secrete testosterone under the control of LH, but the role of the fetal pituitary in regulating fetal Leydig cell function is unclear. To study the early relationship between pituitary and Leydig cell function, we have examined the development of fetal pituitary LH levels and Leydig cell function in normal mice and in hypogonadal (hpg) mice that lack GnRH and, thus, circulating gonadotropins. In normal and hpg mice, pituitary LH content was barely detectable until embryonic day 17 (E17), when levels began to increase significantly in both groups. Pituitary levels of LH in hpg mice were, however, only about 10% of normal at all ages. Full-length LH receptor transcripts were first detectable in fetal testes on E16 in both normal and hpg mice. In normal mice, levels of testicular messenger RNA (mRNA) encoding cytochrome P450 side-chain cleavage and 17alpha-hydroxylase increased from E13 to reach a peak around birth. In hpg mice, levels of mRNA encoding these enzymes were normal until around birth, at which time there was a significant decline. Levels of testicular mRNA encoding 3beta-hydroxysteroid dehydrogenase type I were similar in normal and hpg mice and showed little change during development. Intratesticular testosterone reached a peak on E18 in normal animals before declining again after birth. In hpg mice, intratesticular testosterone levels were normal throughout fetal development and on the day of birth, but were barely detectable by postnatal day 5. Results show 1) that fetal Leydig cell function in the mouse is normal in the absence of endogenous circulating gonadotropins; 2) that Leydig cells become dependent on gonadotropins shortly after birth; and 3) that pituitary LH synthesis can start in the absence of GnRH but is dependent on LH for a normal level of synthesis and secretion.