Expression of activin/inhibin receptor and binding protein genes and regulation of activin/inhibin peptide secretion in human adrenocortical cells.
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 alpha-, betaA/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.
Vänttinen
Teemu
T
Department of Pediatrics, Kuopio University and University Hospital, Kuopio FIN-70211, Finland.
Kuulasmaa
Tiina
T
Liu
Jianqi
J
Voutilainen
Raimo
R
D029404:Activin Receptors / Q000235:genetics*; D030201:Activin Receptors, Type I / Q000235:genetics*; D030301:Activin Receptors, Type II / Q000235:genetics*; D028341:Activins / Q000235:genetics* / Q000494:pharmacology; D000302:Adrenal Cortex / Q000378:metabolism*; D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D005333:Fetus; D005786:Gene Expression Regulation; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D028322:Inhibin-beta Subunits / Q000494:pharmacology; D007265:Inhibins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D021122:Protein Subunits; D011506:Proteins; D012333:RNA, Messenger / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D002352:Carrier Proteins; D017931:DNA Primers; D021122:Protein Subunits; D011506:Proteins; D012333:RNA, Messenger; D018000:Receptors, Peptide; C422405:activin A; C422362:inhibin A; C422364:inhibin B; D028341:Activins; D007265:Inhibins; D028322:Inhibin-beta Subunits; C425423:ACVR1 protein, human; D029404:Activin Receptors; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A; D006854:Hydrocortisone