Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins.

We have observed that familial factors have a decided influence on the plasma content of sex steroids in men both in the general population and in men of families with prostatic cancer. The contribution of genetic and nongenetic familial factors on the variation of plasma sex steroid content and action has now been investigated in 75 pairs of normal male monozygotic (MZ) twins and 88 pairs of dizygotic (DZ) twins. Zygosity was determined by measuring ten blood proteins and enzymes. The mean plasma values for testosterone (T), dihydrotestosterone (DHT), estradiol (E2), estrone (E1), and 3 alpha-androstanediol glucuronide (3 alpha-diol G), free T, LH, FSH, SHBG, age, and degree of adiposity were all similar between the groups of twins. Familial factors (P less than 0.01) accounted for 50% or more of the variation in plasma hormone levels in MZ twins (3 alpha-diol G, 84%; T/DHT, 70%; T, 63%; E1, 63%; free T, 61%; E2, 57%; DHT, 56%; LH, 55%; and FSH, 54%) except for SHBG, which was 30%. The familial influence was greater in MZ twins than in DZ twins for all measurements except for SHBG. The heritability of the variation of hormone levels in plasma was determined from the equation: 2[rMZ(intraclass correlation) - rDZ]. Genes regulate 25% to 76% of the total variation of plasma content of the hormones except for DHT (12%) and SHBG (less than 1%). Genetic regulation of tissue DHT formation was suggested by observing a 48% genetic effect on the plasma content of 3 alpha-diol G.(ABSTRACT TRUNCATED AT 250 WORDS)