Overexpression of activin-beta A subunit mRNA is associated with decreased activin type II receptor mRNA levels in the testes of alpha-inhibin deficient mice.
Activins and inhibins are polypeptides of the transforming growth factor-beta family that participate in differentiation and growth of diverse cell types, and are involved in endocrine/paracrine regulation of the hypothalamo-pituitary-gonadal axis. Mice with alpha-inhibin subunit gene deletion develop large testicular tumors. In these animals, a 200-fold increase in testicular expression of activin beta A subunit mRNA was detected using S1-nuclease protection analysis. Northern blot analysis demonstrated that a predominant mRNA form of approximately 6.5 kb and a second minor form of 4.5 kb were overexpressed in the testes of the alpha-inhibin deficient animals. Testicular expression of the type II activin receptor was decreased 3-fold in these mice. In contrast, hypothalamic beta A and type II activin receptor mRNA levels remained unaltered. alpha-Inhibin may play a role to suppress the expression of beta A mRNA in the mammalian testes. These results demonstrate that increased expression of activin is accompanied by a tissue specific reduction in the expression of its own receptor mRNA in vivo.
Trudeau
V L
VL
Neurosciences Unit, University of Ottawa, Loeb Medical Research Institute, ON, Canada.
Matzuk
M M
MM
Haché
R J
RJ
Renaud
L P
LP
D029404:Activin Receptors; D028341:Activins; D000591:Amino Acid Isomerases / Q000096:biosynthesis; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis; D004706:Endodeoxyribonucleases / Q000096:biosynthesis; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism*; D007265:Inhibins / Q000096:biosynthesis* / Q000172:deficiency*; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D019696:Peptidylprolyl Isomerase; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D013737:Testis / Q000378:metabolism*
D002352:Carrier Proteins; D046911:Macromolecular Substances; D015347:RNA Probes; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; D004706:Endodeoxyribonucleases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase