Inhibin subunit expression has recently been shown to occur in rat and sheep adrenals. We now show the presence of inhibin subunit mRNAs in human fetal and adult adrenal tissue specimens and cultured adrenocortical cells. Northern blot analysis revealed that inhibin alpha-subunit gene is as strongly expressed in fetal adrenals as in fetal testes, whereas adult adrenals expressed alpha-subunit mRNA to a lesser extent. beta A-Subunit mRNA was detectable in placenta, and beta B mRNA was found in testes. With reverse transcription-polymerase chain reaction analysis all inhibin subunit mRNAs (alpha, beta A, and beta B) could be found in fetal adrenal samples. In cultured fetal and adult adrenal cells ACTH and dibutyryl cAMP increased inhibin alpha-subunit mRNA 3- to 4-fold. beta A mRNA was spontaneously induced in cultured adrenal cells. 12-O-Tetradecanoyl phorbol-13-acetate, a protein kinase-C regulator, increased beta A mRNA levels 9.6- and 3.3-fold in fetal and adult adrenal cultures, respectively. 12-O-Tetradecanoyl phorbol-13-acetate treatment abolished ACTH-induced alpha-subunit mRNA accumulation in both fetal and adult cultures. Our results show that inhibin genes are expressed in human fetal adrenals and testes during the second trimester of gestation. Adult adrenals also express inhibin genes, although to a lesser extent than fetal adrenals. Both cAMP- and protein kinase-C-dependent pathways regulate inhibin subunit gene expression in adrenocortical cells. These findings suggest that inhibins/activins are produced locally in human adrenals, where they could function as paracrine or autocrine regulators of adrenal growth and steroidogenesis.