Differentiation of Steroid Biosynthetic Pathways in Developing Testes1, 2

Abstract

Studies reported deal with elucidation of the steroid biosynthetic activity in testicular tissue during differentiation and following hypophysectomy and after treatment with gonadotropins. Testes of animals were removed and 50 mg samples of testicular tissue prepared. Techniques used are described. Tissue from 1- 13- 17- 20- 40- and 90-day-old rats was used. Testes tissue from 1-day-old rats converted 59% of progesterone to testosterone. The degree of conversion diminished with increase in age to a trace in 20-day-old rats. Later this capacity gradually returned. In 90-day-old rats conversion was similar to that of newborn rats. Progesterone was metabolized to the same degree (97-99%) regardless of the age of the animals. As the capacity to convert progesterone to testosterone diminished postnatally androsterone appeared with a peak in 20-day-old rats followed by diminution to 0 in 90-day-old rats. Only a small percentage of progesterone was converted to androstenedione. Also androstenediol was formed from progesterone in incubates of testicular tissue from 20-day-old rats. Only 15% of testosterone was metabolized by testicular tissue from 1-day-old rats the major metabolite being androstenedione. Tissue from 20-day-old rats metabolized 48% of testosterone the major metabolite being androsterone (37%). Only 2% was converted to androsten edione. Tissue from 90-day-old rats metabolized 31% of testosterone the major metabolite being androstenedione (19%). Groups of hypophysect omized rats were killed from 3 to 40 days after the operation and tissue incubated as in previous studies. At 3-5 days after the operation levels of conversion of progesterone to testosterone were comparable to those observed in incubates with tissue of newborn or of adult rats. However a different metabolite was observed i.e. 20alpha-hydroxyprogesterone. The amount of testosterone being formed diminished after hypophysectomy while the amount of progesterone not metabolized increased. The major metabolite was 20alpha-hydroxyprogesterone. Metabolism of progesterone by testicular tissue from hypophysectomized rats treated daily with 100 IU of human chorionic gonadotropin (HCG) for 10 or 20 days was studied. After 10 days of HCG treatment the sex accessories were markedly stimulated. A large proportion of progesterone remained unmetabolized and only a small amount of testosterone was formed. It is concluded that the differentiation of steroid biosynthetic pathways involves a complicated pattern of stimulation and repression of enzyme synthesis. The state of biosynthetic activity in the testes after hypophysectomy is unlike that present in the immature animal. HCG given to hypophysectomized animals after the Leydig cells have atrophied does not reinstate biosynthetic activity in a normal pattern. At certain stages testosterone is catabolized to other androgens.