Hormonally Regulated Inhibin Gene Expression in Human Fetal and Adult Adrenals*

Abstract

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.

Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm

“…We also showed negative inhibin immunostaining in the zona glomerulosa, weak staining in the zona fasciculata, and very strong staining in the zona reticularis. The slightly higher (though not significantly) inhibin subunit gene expression detected in hyperplastic compared with normal adrenals could be explained by increased ACTH action on inhibin subunit gene expression (Voutilainen et al 1991) in hyperplastic adrenals. Alternatively, but less likely, this difference could be caused by a higher cortical to medullary tissue ratio in hyperplastic than in normal adrenals.…”

“…Both inhibin and subunit mRNA species and peptides can be detected in adrenal cortex, but not in the medulla (Meunier et al 1988, Voutilainen et al 1991, Spencer et al 1992, McCluggage et al 1998. The first reports suggested all adrenocortical tumours to be inhibin positive (Chivite et al 1998, McCluggage et al 1998.…”

“…Steroid-producing organs, pituitary gland, placenta and the central nervous system are the main sites of inhibin subunit gene expression (Meunier et al 1988, Voutilainen 1995. In humans, inhibin subunit gene is expressed in both foetal and adult adrenal cortex (Voutilainen et al 1991, Spencer et al 1992, and the inner zones, particularly the zona reticularis, have the strongest immunoreactivity with anti-inhibin antibody (Chivite et al 1998, McCluggage et al 1998. The role of adrenal inhibins is not fully understood.…”

“…The role of adrenal inhibins is not fully understood. Adrenocorticotrophic hormone (ACTH) has been shown to upregulate the expression of adrenal inhibins in vitro (Crawford et al 1987, Voutilainen et al 1991. A negative autoregulation of inhibin subunit expression was suggested in a transgenic mouse study, where gonadal inhibins were shown to downregulate the expression of the inhibin subunit gene in the adrenal gland (Kananen et al 1996).…”

Second trimester levels of maternal serum total activin A and placental inhibin/activin alpha and betaA subunit messenger ribonucleic acids in Down syndrome pregnancy

“…Specific oligonucleotide primers designed to amplify sequences of inhibin/activin bA, inhibin a subunit (18) and GAPDH (19) cDNAs are shown in Table 1. Computer analysis performed to study the possible secondary structure of the different cDNAs and to compare the synthesized oligomers with the human sequences in the MicroGenie (Beckman, Palo Alto, CA, USA) gene database bank revealed no more than 74% homology in the former and 72% in the latter among all other genes.…”