Corticotropin-releasing hormone as adrenal androgen secretagogue

The regulation of adrenarche is one of the enigmas of pediatric endocrinolo gy. Adrenarche is thought to be governed by a dual control mechanism in whi ch an adrenal androgen secretagogue acts upon a zona reticularis primed by ACTH. We hy pothesized that corticotropin-releasing hormone (CRH) may serve as adrenal androgen secretagogue. We tested the concept by infusing either saline or human (h) CRH (1 mu g/kg/h in saline) over 3 h, after overnight dexamethasone pretreatment, into eight young men within a randomized, cross -over study design. Serum ACTH and dehydroepiandrosterone-sulfate were meas ured once hourly; DHEA, androstenedione and 17-hydroxy-progesterone were de termined at baseline and after 3 h of saline/hCRH infusion. ACTH levels rem ained unaltered during saline infusion and average ACTH responses amounted to 13 pg/mL (3.3 pmol/L) during hCRH infusion. Neither saline nor hCRH infu sion altered 17-hydroxy-progesterone levels. Serum dehydroepiandrosterone-s ulfate rose swiftly within 3 h of hCRH infusion and remained unchanged afte r saline (mean increase 37 versus 1%; p < 0.01). On average, serum DHEA dou bled and androstenedione tripled during hCRH infusion, although no changes were observed during saline infusion (p < 0.01). In conclusion, CRH appears to have the capacity to act as adrenal androgen secretagogue. We suggest t hat the enigma of adrenarche may have an elegant solution, with CRH and ACT H coupled in sequence at the hypothalamic-pituitary level, and in parallel within the zona reticularis, just as they presumably are within the fetal a drenal, which is exposed to CRH of placental origin.