ANDROGENS AND MASCULINIZATION OF GENITALIA IN THE SPOTTED HYENA (CROCUTA-CROCUTA) - 1 - UROGENITAL MORPHOLOGY AND PLACENTAL ANDROGEN PRODUCTION DURING FETAL LIFE

According to common understanding of sexual differentiation, the forma tion and development of a penile clitoris in female spotted hyaenas re quires the presence of naturally circulating androgens during fetal li fe. The purpose of the present study was to determine potential source (s) of such fetal androgens by investigating the timing of urogenital development and placental production of androgen during early and mid- gestation. Fetuses determined to be female by molecular techniques (la ck of SRY gene) at days 33 and 48 of gestation had undifferentiated go nads, but the clitoris was already 'masculinized' and was generally si milar to the phallus of a 50-day-old male fetus. Wolffian and Mulleria n ducts terminated at the urogenital sinus in both sexes and a urethra was present along the entire length of the clitoris and penis. The ad renal gland was large and histologically differentiated at 33 days. St eroid gradients across the uterus (a drop in Delta(4)-androstenedione, with increases in oestrogen and androgen), and high androstenedione i n ovarian veins indicated that ovarian androstenedione was metabolized and secreted as testosterone by the placenta throughout gestation. In vitro, whole or homogenized placentae at days 48 and 58 of gestation (110 days total) metabolized radiolabelled androstenedione into testos terone and oestradiol; the specific enzymatic activity of early placen tal tissues was higher than at later stages. A human placental homogen ate had higher aromatase activity but did not produce testosterone unl ess aromatase was inhibited. Infusion of labelled androstenedione into the uterine arteries of hyaenas demonstrated the conversion of this s ubstrate into testosterone and oestradiol and their secretion into the fetal circulation. Evidently, androgen is produced by the placenta an d secreted into the fetal circulation from early in pregnancy when mas culinization is first evident, before differentiation of the fetal ova ry.