Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis.
ACTH has been shown to stimulate androgen production by the fetal/neonatal mouse testis through the melanocortin type 2 receptor (MC2R). This study was designed to localize the expression of MC2R in the neonatal mouse testis and characterize the effects of ACTH on testicular androgen production. Using immunohistochemistry, MC2R was localized to the fetal-type Leydig cell population of the neonatal testis. ACTH caused a time-dependent increase in cyclic AMP (cAMP) and testosterone production by isolated cells with an increase in cAMP apparent in < 3 min. There was no additive effect of maximally stimulating doses of ACTH and human chorionic gonadotropin (hCG). Androgen production in response to ACTH and hCG was reduced by UO126 and dexamethasone, which are the inhibitors of ERK1/2 and phospholipase A2 respectively. Expression of mRNA encoding StAR was increased fourfold by both ACTH and hCG, although expression of mRNA encoding for steroidogenic enzymes was not markedly affected. The potency of N-terminal fragments of ACTH to stimulate androgen production was similar to that seen previously in the adrenal. Data indicate that both LH and ACTH, acting through their respective receptors, stimulate steroidogenesis by fetal-type Leydig cells via arachidonic acid, protein kinase A, and ERK1/2 activation of StAR.
Johnston
Heather
H
Division of Cell Sciences, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, UK.
King
Peter J
PJ
O'Shaughnessy
Peter J
PJ
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002070:Butadienes / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003366:Cosyntropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010750:Phosphoproteins / Q000235:genetics; D044103:Receptor, Melanocortin, Type 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000196:embryology; D013739:Testosterone / Q000096:biosynthesis*; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
D002070:Butadienes; D006063:Chorionic Gonadotropin; D009570:Nitriles; D010446:Peptide Fragments; D010750:Phosphoproteins; D044103:Receptor, Melanocortin, Type 2; C113580:U 0126; D000098682:Steroidogenic Acute Regulatory Protein; D003366:Cosyntropin; D013739:Testosterone; C039322:ACTH (1-16); D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D020929:Mitogen-Activated Protein Kinase Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; C028238:ACTH (1-17)