Functional zonation of the midgestation human fetal adrenal cortex: fetal versus definitive zone use of progesterone for cortisol synthesis.

Studies of human fetal adrenal function and its control have revolved mainly around the remarkable capacity of the unique fetal zone of this gland to elaborate dehydroepiandrosterone sulfate. Another important function of the fetal adrenal, however, is its production of cortisol. Because the human fetal adrenal is deficient in 3 beta-hydroxysteroid dehydrogenase activity, cortisol has been thought to be formed from circulating progesterone. To further investigate this hypothesis, cortisol production by separated fetal and definitive zones of the midgestation human fetal adrenal in organ culture has been examined in the absence and presence of varying concentrations of progesterone and adrenocorticotropic hormone. Cortisol was measured by radioimmunoassay. In the absence of progesterone, cortisol production by both zones increased gradually over time in culture in response to adrenocorticotropic hormone. In the presence of progesterone, cortisol production by the definitive zone was unchanged. In contrast, the response of the fetal zone to progesterone was immediate: cortisol production increased significantly and remained high throughout the culture period. These results suggest a greater capacity of the fetal zone to utilize progesterone for cortisol production and are consistent with morphologic evidence that the active zone of the midgestation human fetal adrenal is the fetal zone, possessing not only the enzyme activity necessary for dehydroepiandrosterone sulfate production but, except for 3 beta-hydroxysteroid dehydrogenase, that for cortisol production as well.

Progesterone and estrogen production by placental monolayer cultures: effect of dehydroepiandrosterone and luteinizing hormone-releasing hormone.

The effect of dehydroepiandrosterone (DHA) and LRH on estrogen and progesterone production by cultured placental cells has been investigated. Placental monolayer cultures were established by trypsin dispersion of term placental villi and were maintained for 5 days in culture medium containing either no steroid or 10(-7) - 10(-5)M DHA, DHA sulfate (DHAS), or 16 alpha-hydroxy-DHA (16 alpha-OH DHA), in all cases with and without the addition of 2 X 10(-7) or 2 X 10(-6)M LRH. The cultures were changed every 24 h, and the media collected were analyzed for estrogen and progesterone by RIA. 17 beta-Estradiol production was dependent on the presence of DHA or DHAS in the medium and increased in proportion to the concentration of precursor added. Similarly, estriol was produced in proportion to the amount of 16 alpha-OH DHA added to the medium. At the same time, high concentrations (10(-5) M) of DHA and DHAS, but not 16 alpha-OH DHA, markedly suppressed progesterone production. LRH had an inhibitory effect on both progesterone and estrogen output by the cultures. These studies suggest that not only the fetus, through its increasing adrenal production of DHA and DHAS toward term, but the placenta itself, through its production of LRH, could modulate placental steroid synthesis.