Testicular steroid metabolism during development in the normal and hypogonadal mouse.
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 delta 4 pathway, and progesterone, 17 alpha-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 5 alpha-reductase activity during this age range, and 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-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 delta 5 pathway. 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 delta 4 pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheffield
J W
JW
Department of Veterinary Basic Sciences, Royal Veterinary College, London.
O'Shaughnessy
P J
PJ
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D007006:Hypogonadism / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011284:Pregnenolone / Q000378:metabolism; D011372:Progestins / Q000378:metabolism*; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013997:Time Factors
D000728:Androgens; D006063:Chorionic Gonadotropin; D011372:Progestins; D011284:Pregnenolone