Intra-adrenal factors are not involved in the differential control of cortisol and adrenal androgens in human adrenals

Abstract

The differential control of adrenal androgens and cortisol may be due to intra-adrenal factors, which may be age-or sex-related, or due to extra-adrenal factors, such as circulating hormones. The purpose of this study was to identify any intrinsic differences that may exist in steroidogenic production occurring within adrenals obtained from males and 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 of and ACTH-stimulated cortisol, androstenedione and dehydroepiandrosterone (DHEA) were examined in freshly prepared adrenal cell suspensions. Basal and ACTH-stimulated cortisol, androstenedione and DHEA production were similar in adrenals from males and females and did not correlate significantly with age when the whole group was examined. When steroidogenesis in male and female adrenals was examined separately against age, a significant correlation was observed only for basal and ACTH-stimulated androstenedione in adrenals from males in the younger age group, 5-30 years (basal: r ¼ 0.84, P ¼ 0.0001; ACTH-stimulated: r ¼ 0.52, P ¼ 0.007). Examination of the relationships between the steroids disclosed that the basal and ACTH-stimulated cortisol/androgen ratios did not correlate significantly with age, but the androstenedione/DHEA ratio showed a significant direct relationship with age in males only (basal: r ¼ 0.53, P ¼ 0.006; ACTH-stimulated: r ¼ 0.5, P=0.01).These data suggest that the influences of sex and age are minor in the modulation of adrenal steroidogenesis and support the concept that extra-adrenal factors dominate in the differential modulation of adrenal androgens and cortisol. The relationship between the androstenedione/ DHEA ratio and increasing age in men is consistent with the recently reported stimulatory effect of testosterone on adrenal steroidogenesis by induction of the conversion of DHEA to androstenedione.

Testosterone Increases Circulating Dehydroepiandrosterone Sulfate Levels in the Male Rhesus Macaque

“…However, in humans the male and female ZR are similar in both size and cytochrome b5 expression (27). Also, cultured male and female adrenal glands respond with identical levels of DHEA secretion when stimulated by ACTH (2). Further, females receiving long-term treatment with T show an increased response of DHEA to ACTH stimulation as compared to female controls (28, 29), suggesting that the adrenal machinery is the same in males and females, but the hormonal input from the HPG axis can modulate adrenal output.…”

“…It is clear, however, that the gross, cellular, and molecular adrenal structure of males and females is essentially similar, suggesting that some factor outside the adrenal gland is responsible for the greater secretion of DHEA/S in males (2). Given that the sex differences in DHEA/S are most pronounced during early adulthood, it is plausible that the different levels of sex-steroid hormones between adult males and females may play a contributing role.…”

Sex-specific Cortisol and Sex Steroids Responses in Stressed Sockeye Salmon during Spawning Period

“…In mammals, over 45 steroids including androgens have been isolated and chemically characterized from adrenal gland extracts, and studied on the function (Norman and Litwack, 1997). Recently, Fearon et al (1998) reported that the differential control of adrenal androgens and cortisol in human. Thus, the existence of interrenal androgen may be needed to consider on the relationship between the function of HIP axis and stress in teleost.…”

Androgen Secretion in Ectopic ACTH Syndrome and in Cushing’s Disease: Modifications Before and After Surgery

“…Extraadrenal factors (such as prolactin, growth hormone, insulin, cytokines, sex steroids and pituitary POMC-derived peptides, such as b-endorphin and joining peptide) may also explain the variation in production of cortisol and androgens by controlling adrenal androgen biosynthesis and secretion. Recently, it was shown that adrenal androgen production does not correlate with age and sex, suggesting that extraadrenal rather than intraadrenal factors may modulate cortisol and androgen production [16].…”