Lower Serum Androstenedione Levels in Pre-Rheumatoid Arthritis versus Normal Control Women: Correlations with Lower Serum Cortisol Levels

Figure 1

A simplified schema of the major adrenal and sex steroids, emphasizing the biosynthetic pathways leading to mineralocorticoids, glucocorticoids, adrenal androgens (AAs), and sex steroids. Initial conversion from cholesterol to pregnenolone is acutely controlled by ACTH, which chronically activates genes promoting other enzymes in the biosynthetic steps. The adrenal cortical volume increases during pre-pubertal adrenarche until young adulthood, particularly in the zona reticularis (ZR), along with its greater AA production, including DHEA, DHEAS, and androstenedione. Individual variability occurs in serum DHEAS levels, being lower in adult females than males, particularly after menopause (adrenopause). Serum AAs progressively decline with aging and are presumably accompanied by diminishing ZR mass. To the contrary, cortisol is derived from the zona fasciculata (ZF) and its levels remain stable over the ages, as does the ZF mass.