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Control of steroid synthesis in human fetal adrenals in mono layer culture



Control of steroid synthesis in human fetal adrenals in mono layer culture



Canadian Journal of Biochemistry 56(6): 577-584



The actions of ACTH, N6,O2-dibutyryl adenosine-3',5'-cyclic phosphate (dbcAMP) and human chorionic gonadotropin (hCG) on the sulfation of DHA [dehydroisoandrosterone] and the synthesis of cortisol by human fetal adrenal cells in monolayer culture were described. EM studies indicate that the cells present in cultures at the end of 5 days were intact and had many of the characteristics of secretory cells. Sulfation of DHA was strongly inhibited by 11-deoxycorticosterone, testosterone, androsterone and dihydrotestosterone. Very small effects were observed with progesterone and corticosterone and insignificant effects with estrone, estradiol and estriol. Androstenedione and 17.alpha.-hydroxylated corticosteroids showed no inhibition. When used as substrate, C21 .DELTA.4-3-ketosteroids were good precursors of cortisol with 11-deoxycortisol being the best one followed by 17.alpha.-hydroxyprogesterone and progesterone. The conversion of progesterone (4 .mu.g/2 ml) to cortisol was 5-fold greater than under conditions where no substrate was present (endogenous production). ACTH in the concentration of 5 .times. 10-4 U[unit]/ml added twice daily to the cell cultures for 8 days increased 8-fold the sulfation of DHA and increased cortisol synthesis from progesterone 35-fold in 5 days. The addition of dbcAMP (5 .times. 10-5 M) or hCG used at 2.0 or 0.2 U/ml did not stimulate the sulfation of DHA. A lag period of at least 36 h was required before the stimulation of DHA sulfation or cortisol synthesis from progesterone was observed. Apparently dbcAMP stimulates the conversion of progesterone, 17.alpha.-hydroxyprogesterone and 11-deoxycortisol to cortisol by the adrenal cells. While 11.beta.- and 21-hydroxylation was stimulated by dbcAMP, 17.alpha.-hydroxylation was apparently not altered.

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Accession: 005051337

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PMID: 208729


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