INTRA-ADRENAL FACTORS ARE NOT INVOLVED IN THE DIFFERENTIAL CONTROL OFCORTISOL AND ADRENAL ANDROGENS IN HUMAN ADRENALS

The differential control of adrenal androgens and cortisol mag be due to intra-adrenal factors, which may be age-or sex-related, or due to e xtra-adrenal factors, such as circulating hormones. The purpose of thi s study was to identify any intrinsic differences that may exist in st eroidogenic production occurring within adrenals obtained from males a nd females, and any maturational differences that may evolve with age. Using human adrenals from 48 transplant donors (32 males, 16 females; ages 5-60 years), the influences of age and sex on basal production o f and ACTH-stimulated cortisol, androstenedione and dehydroepiandroste rone (DHEA) were examined in freshly prepared adrenal cell suspensions . Basal and ACTH-stimulated cortisol, androstenedione and DHEA product ion were similar in adrenals from males and females and did not correl ate significantly with age when the whole group was examined. When ste roidogenesis in male and female adrenals was examined separately again st age, a significant correlation was observed only for basal; and ACT H-stimulated androstenedione in adrenals from males in the younger age group, 5-30 years (basal: r=0.84, P=0.0001; ACTH-stimulated: r=0.52, P=0.007). Examination of the relationships between the steroids disclo sed that the basal and ACTH-stimulated cortisol/androgen ratios did no t correlate significantly with age, but the androstenedione/DHEA ratio showed a significant direct relationship with age in males only (basa l: r=0.53, P=0.006; ACTH-stimulated: r=0.5, P=0.01). These data sugges t that the influences of sex and age are minor in the modulation of ad renal steroidogenesis and support the concept that extra-adrenal facto rs dominate in the differential modulation of adrenal androgens and co rtisol. The relationship between the androstenedione/DHEA ratio and in creasing age in men is consistent with the recently reported stimulato ry effect of testosterone on adrenal steroidogenesis by induction of t he conversion of DHEA to androstenedione.