We tested the hypothesis that adrenal androgen production is supported by a pituitary factor distinct from ACTH. Six adult male chimpanzees who had completed adrenal maturation (adrenarche) were castrated and either hypophysectomized or sham hypophysectomized. Hypophysectomized animals received synthetic ACTH-(1-24) and T4 to prevent adrenal insufficiency and hypothyroidism. Adrenal function was evaluated with a 3-h ACTH infusion before and 7, 21, 40, 120, and 180 days after hypophysectomy. Plasma cortisol (F), dehydroepiandrosterone (DHA), DHA sulfate (DHAS), and androstenedione (Δ4A) were measured at six time points during the ACTH infusions. The mean ratios of DHA to F, DHAS to F and Δ4A to F during ACTH infusion were calculated as indices of the relative activity of the androgen pathway compared to that of the cortisol pathway. The DHA to F ratio during ACTH infusion was 31% of the pretreatment level 40 days after hypophysectomy (P < 0.01 compared to the sham-hypophysectomized controls). The DHAS to F ratio during ACTH infusion, which paralleled the DHA to F ratio, also fell significantly (P < 0.025). Hypophysectomy did not alter the Δ4A to F ratio. None of the ratios was altered by sham hypophysectomy. MCRs for F and DHA, which were measured before and 180 days after hypophysectomy or sham hypophysectomy, did not change significantly. Additionally, plasma corticosteroid-binding globulin levels remained unchanged throughout the study for both groups of chimpanzees. Thus, the changes in the DHA to F ratio cannot be explained by alterations in the MCRs of DHA or F or in the plasma transport protein for F. These data suggest that ACTH maintained normal F and Δ4A secretion after hypophysectomy but failed to maintain normal DHA and DHAS secretion. This is consistent with the hypothesis that normal Δ5-adrenal androgen secretion is dependent upon a non-ACTH pituitary factor or with the hypothesis of different ACTH requirements for the maintenance of F and Δ5-adrenal androgen secretion.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical