The human fetal adrenal gland is primarily composed of fetal zone cells, which exhibit a high rate of steroidogenesis and a rapid growth rate during fetal life. α-Human atrial natriuretic polypeptide has been shown to inhibit basal and adrenocorticotropic hormone-stimulated steroidogenesis in the human adult and in some human adrenal adenoma cells. The purpose of this investigation was to determine the effect of atrial natriuretic polypeptide on steroidogenesis by fetal zone cells. Dispersed fetal zone cells were incubated in Krebs-Ringer's medium with adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate and in the presence of atrial natriuretic polypeptide. The medium was analyzed for content of dehydroepiandrosterone sulfate and cortisol by radioimmunoassay. The addition of adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate increased the secretion of dehydroepiandrosterone sulfate and cortisol twofold to threefold and twofold to sixfold, respectively, above basal rates. Atrial natriuretic polypeptide significantly inhibited basal dehydroepiandrosterone sulfate and cortisol secretion. When cells were incubated in the presence of adrenocorticotropic hormone, forskolin, 22R-hydroxycholesterol, or dibutyryl cyclic adenosine monophosphate plus atrial natriuretic polypeptide, cortisol secretion was inhibited 50% to 90% and dehydroepiandrosterone sulfate was inhibited 25% to 50%. Atrial natriuretic polypeptide had no effect on the metabolism of progesterone tagged with carbon 14 in fetal zone cells. In conclusion, atrial natriuretic polypeptide inhibited basal and adrenocorticotropic hormone-stimulated steroid secretion by fetal zone cells. Furthermore, these results suggested that the action of atrial natriuretic polypeptide was by inhibition of cholesterol side-chain cleavage or transfer of cholesterol to the mitochondrion.
- Atrial natriuretic polypeptide
- adrenal gland
- fetal zone cells
ASJC Scopus subject areas
- Obstetrics and Gynecology