Acth and sulfatase activity

Abstract

The conversion of 5-en-3β-ol steroid sulfates to active hormones has been extensively studied. A preliminary desulfation of the precursors is required to allow their structure 5-ene-3β (-ol to be transformed to the configuration 4-ene-3-keto present in active hormones. Steroid sulfatase is a very active enzyme but present at a very low concentration with respect to other steroid biosynthesizing enzymes in the adrenal tissue. It represents a limiting enzyme reaction in corticoid production from early precursors. Steroid sulfatase hydrolyzes pregnenolone-sulfate (P-S) much more effectively than DHEA-sulfate (D-S). Its activity and concentration in the adrenal is increased by in vivo stimulation with ACTH, however, ACTH does not seem to stimulate other enzyme reactions after free pregnenolone. Both P-S and D-S act on the steroid sulfatase inhibiting reciprocally the desulfation of the other, in such a way that when both sulfates are present simultaneously, P-S is efficiently hydrolyzed to release free P which is quickly converted to progesterone and corticoids, while most of D-S remains as sulfate and is excreted as such. Measurements of the endogeneous pools of steroid precursors in the adrenal show that, ACTH stimulation decreases the levels of P-S, while free P increases first and then decreases as it is converted to progesterone and corticoids. ACTH may have two parallel but distinct mechanisms of action on corticoid biosynthesis. One, already established, is through the activation of adenylcyclase, c-AMP release and a final increment of TPNH to favor adrenal hydroxylations and side chain cleavages. The other, to be demonstrated as yet, suggests a stimulation of steroid sulfatase without c-AMP participation and regulates the amount of free 5-en-3β-ol steroid available for active hormone biosynthesis.