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The ability of cells from the zona fasciculata and the zona reticularis of the human adrenal cortex to transform labelled pregnenolone and progesterone to cortisol in vitro was investigated. Examination of the ³H:¹⁴C ratios of 16-hydroxyprogesterone, 17-hydroxyprogesterone, 11-deoxycorticosterone and cortisol formed during incubations in vitro suggested that the role of progesterone in the transformation of pregnenolone to cortisol might be a relatively minor one.

An attempt was subsequently made to estimate the relative importance of the biosynthetic pathway to cortisol by way of progesterone in hyperplastic adrenal tissue by a mathematical approach.