Testicular steroid metabolism during development in the normal and hypogonadal mouse

Abstract

ABSTRACT The patterns of testicular steroidogenesis were investigated during postnatal development in the normal mouse and in the hypogonadal (hpg) mouse from 20 days. The hpg mouse lacks GnRH and may be used to examine the function of this peptide in normal gonadal development. Testicular tissue was incubated with [3H]pregnenolone and metabolites were separated by thin-layer chromatography and high-performance liquid chromatography. In the normal mouse from 1 to 10 days, metabolism occurred predominantly through the Δ4 pathway, and progesterone, 17α-hydroxyprogesterone, androstenedione and testosterone were the main metabolites formed, together with significant amounts of an unidentified polar steroid. Between 15 and 25 days, androstenedione became the major metabolite formed from pregnenolone. There was also a marked increase in 5α-reductase activity during this age range, and 5α-dihydrotestosterone and 5α-androstane-3α, 17β-diol were significant metabolites. In normal animals older than 30 days, testosterone became the major metabolite, and between 30 days and adulthood the pattern of metabolism changed significantly due to increased formation of intermediates from the Δ5pathway. In the hpg mouse between 20 and 30 days, the pattern of steroid metabolism was unlike that of any age of the normal animal. Progesterone was the major metabolite formed and dehydroisoandrosterone was the major C19 steroid formed, although significant levels of androstenedione and testosterone were also formed. After 30 days there was a marked decrease in steroid metabolism, with androstenedione (the major androgen) being formed mainly through the Δ4 pathway. Addition of human chorionic gonadotrophin to tissue from normal or hpg animals had little effect on the pattern of metabolism, except in the 10- and 20-day-old normal animal where there was an increased accumulation of progesterone. These results indicate that in the normal mouse the major testicular steroidogenic pathways show significant changes during development. In the hpg mouse the steroidogenic pathways are markedly different from those in normal animals, indicating the importance of the gonadotrophins in controlling the pattern of steroidogenesis. The change in the testicular steroidogenic pattern during development in the hpg mouse may also indicate, however, that these testes are under some stimulation during early postnatal development. J. Endocr. (1988) 119, 257–264