Expression of Activin/Inhibin Receptor and Binding Protein Genes and Regulation of Activin/Inhibin Peptide Secretion in Human Adrenocortical Cells

• Published in: The journal of clinical endocrinology and metabolism Vol. 87; no. 9; pp. 4257 - 4263
• Main Authors: Vänttinen, Teemu, Kuulasmaa, Tiina, Liu, Jianqi, Voutilainen, Raimo
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-09-2002
• Subjects: Activin Receptors - genetics; Activin Receptors, Type I - genetics; Activin Receptors, Type II - genetics; Activins - genetics; Activins - pharmacology; Adrenal Cortex - metabolism; Adrenals. Interrenals; Adrenocortical hormones. Regulation; Adult; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Cell Line; DNA Primers; Fetus; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humans; Hydrocortisone - metabolism; Inhibin-beta Subunits - pharmacology; Inhibins - genetics; Polymerase Chain Reaction; Protein Subunits; Proteins; Receptors, Peptide - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Transcription, Genetic; Vertebrates: endocrinology; Human; Cell culture; Protein kinase C; Adrenal glands; Enzyme; Transferases; Inhibin; Gene expression; Endocrine secretion; Binding protein; Adrenocorticotropic hormone; Adenohypophyseal hormone; Enzymatic activity; Hormonal regulation; Activin; Reverse transcription polymerase chain reaction; Hormonal receptor
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-020460

Activins and inhibins are glycoprotein hormones produced mainly in gonads but also in other organs. They are believed to be important para/autocrine regulators of various cell functions. We investigated activin/inhibin receptor and binding protein gene expression and the regulation of activin/inhibin secretion in human adrenal cells. RT-PCR revealed inhibin/activin α-, βA/B-subunit, follistatin, activin type I/II receptor, and inhibin receptor (betaglycan and inhibin-binding protein) mRNA expression in fetal and adult adrenals and cultured adrenocortical cells. Cultured cells secreted activin A and inhibin A/B as determined by specific ELISAs. ACTH stimulated inhibin A/B secretion in fetal (1.8- and 1.8-fold of control, respectively) and in adult cells (3.4- and 1.7-fold of control, respectively) without significant effect on activin A. 8-bromoadenosine cAMP (protein kinase A activator) increased activin A and inhibin A/B secretion in the human adrenocortical NCI-H295R cell line (32-, 17-, and 3-fold of control, respectively). 12-O-tetradecanoyl phorbol-13-acetate (protein kinase C activator) stimulated both activin A and inhibin A secretion (764- and 32-fold of control, respectively), and activin treatment increased inhibin B secretion in these cells (25-fold of control). In conclusion, human adrenocortical cells produce dimeric activins and inhibins. ACTH stimulates inhibin secretion and decreases activin/inhibin secretion ratio, probably via the protein kinase A signal transduction pathway. This, together with the adrenocortical activin/ inhibin receptor and binding protein expression, suggests a physiological role for activins and inhibins in the human adrenal gland.