Male and female human embryos develop identically during the first phase of gestation. The indifferent gonads then differentiate into ovaries or testes and soon begin to secrete their characteristic hormones. If ovaries (or no gonads) are present the final phenotype is female; thus no gonadal hormones are required for female development during embryogenesis. Two hormones of the fetal testis—Müllerian regression hormone and testosterone—are responsible for the formation of the male phenotype. Analysis of fibroblasts from the skin of patients with abnormalities of sexual development due to single gene defects shows that testosterone is responsible for virilization of the male internal genital tract, that its derivative dihydrotestosterone causes development of the male external genitalia, and that both hormones act in the embryo by the same receptor mechanisms operative in postnatal life.

The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha-reductase, decreases serum dihydrotestosterone levels, but has little effect on serum testosterone. The current study was designed to assess the effect of finasteride on dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or 100 mg/day finasteride for 7 days before transurethral resection of the prostate. In the placebo group the mean concentration of prostatic dihydrotestosterone was 10.3 +/- 0.6 nmol/kg (+/- SE), and the mean concentration of testosterone was 0.7 +/- 0.1 nmol/kg. After 7 days of treatment with all doses of finasteride, prostatic dihydrotestosterone declined to 15% or less of control levels, and the testosterone concentration increased in a reciprocal fashion. Compared to the placebo group, there was no significant difference in the mean prostatic dihydrotestosterone level achieved in any of the finasteride-treated groups. However, prostatic dihydrotestosterone levels were lower in the groups receiving higher doses of the drug. In two additional patients, finasteride treatment for 2 days also caused a decrease in prostatic dihydrotestosterone levels. No significant adverse experiences occurred during the study. We conclude that finasteride causes profound decrease in prostatic dihydrotestosterone.

The gonads of the tammar wallaby, Macropus eugenii, are sexually indifferent at birth (Day 0) despite the fact that phenotypic sexual differentiation has already commenced as evidenced by the presence of a scrotum in males and mammary anlagen in females. The seminiferous cords of the testis first become clearly recognizable on Day 2 of pouch life, and ovarian differentiation is recognizable by Day 10. To monitor the endocrine development of the gonads during sexual differentiation of the urogenital tract, we measured the steroid hormone content in 92 pools of gonads from male and female tammar pouch young from the day of birth to 206 days of pouch life. Progesterone, estradiol, and dihydrotestosterone concentrations were low (less than 0.05 ng/mg protein) in both ovaries and testes at all stages examined, and testosterone concentrations were uniformly low in ovaries. Testosterone concentrations in testes were low on Days 0-4, averaging about 0.2 ng/mg protein; they rose by Days 5-10 to an average of 0.9 ng/mg protein, remained elevated until about Day 40, and thereafter fell to values similar to those in the ovaries. The phallus and urogenital sinus were able to convert testosterone to dihydrotestosterone from the earliest stages examined (Days 10 and 11). Thus in the tammar wallaby, as in eutherian mammals, testosterone is the androgen secreted by the developing testis, and dihydrotestosterone is formed in certain androgen target tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of castration and dihydrotestosterone (DHT) treatment on levels of skeletal muscle androgen receptor (AR) were examined in three groups of adult male rats: 1) intact normal rats, 2) rats castrated at 16 wk of age, and 3) rats castrated at 16 wk of age and given DHT for 1 wk starting at week 17. All animals were killed at 18 wk of age. Castration caused a decrease (P < 0.05) in the weights of the levator ani and bulbocavernosus muscles. The administration of DHT to the castrated rats increased (P < 0.05) the weights of the levator ani and bulbocavernosus muscles. Castration caused a significant downregulation of AR levels in the bulbocavernosus (P < 0.05) but had no significant effect on AR levels in the levator ani muscle. DHT administration to the castrated group upregulated AR levels in the bulbocavernosus and levator ani muscles. The plantaris muscle did not significantly (P > 0.05) change for any of the treatments. These findings suggest that the effects of castration and androgen replacement differentially affect skeletal muscle mass and AR levels.

We assessed the activity of the aromatase enzyme complex in slices of brain from rats by measuring the release of 3H2O from [1 beta-3H]testosterone. In hypothalami from 12-day-old rats, the rate of aromatase activity was linear with time and amount of tissue. The reaction was saturated at a substrate concentration of 0.1 microM, and the apparent Km of the reaction was 27 nM. The production of 3H2O was inhibited by 4-hydroxyandrostenedione, with an apparent Ki of 20 nM. Aromatase activity was first detected in the diencephalon of 16-day-old fetuses and reached maximum rates in hypothalamic tissue between days 18 and 20 of gestation. The highest rate of activity per mg protein (approximately 4.8 pmol h-1 mg protein-1) was observed in the preoptic area (POA) on the 20th day of embryonic development. However, when expressed as a rate per tissue fragment, aromatase activity was as high in the medial basal hypothalamus as in the POA. After day 20 of gestation aromatase activity rapidly decreased in the POA and medial basal hypothalamus of both males and females. The lowest levels were observed between postnatal days 16 and 20. Aromatase activity was not detectable in cerebral cortex and cerebellum at any age studied. Since serum testosterone was higher in males than females during the first 4 days of postnatal life, and since aromatase activity is elevated in the hypothalamus at this time, our results support the current concept that local formation of estrogen mediates testosterone-induced masculinization of the brain during the neonatal period. However, our results also indicate that failure of the rat brain to undergo complete sexual differentiation before birth cannot be due to an inability of the fetal hypothalamus to aromatize androgens, since aromatase activity was higher in the hypothalamus than in any other fetal tissue.