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Title: DEVELOPMENTAL REGULATION OF CYTOCHROME P450 17ALPHA-HYDROXYLASE/C17-20 LYASE AND 3BETA-HYDROXYSTEROID DEHYDROGENASE- ISOMERASE MESSENGER RIBO- NUCLEIC ACID EXPRESSION & ACTIVITY DURING SEXUAL MATURATION IN RAT TESTIS

Author
item MACK, SERDIA - HOWARD UNIVERSITY
item Garrett, Wesley
item Guthrie, Howard

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/5/2000
Publication Date: N/A
Citation: N/A

Interpretive Summary: There is considerable variation in development of male sex characteristics, sperm quality, and sperm production which may be related to critical production of testosterone during pubertal development in swine. Knowledge is lacking concerning the expression pattern of two genes which encode enzymes in the metabolic pathway for production of testosterone in the testis. The expression of messenger ribonucleic acid encoding 3beta- hydroxysteroid dehydrogenase/delta 5-4 isomerase and cytochrome P450 17alpha-hydroxylase/C17-20 lyase was measured by in situ hybridization to understand the basis for changes in steroidogenesis known to occur during pubertal development using the male rat as an experimental model. These enzymes were expressed abundantly by clusters of Leydig cells in 21 and 28 day old immature animals. However, during pubertal development, expression decreased to undetectable levels at 45 and 60 and at 60 days of age, respectively, even though rats secreted increasing amounts of testosterone during this time and testis tissue could produce the steroids in culture. In the adult testis at 90 days of age, expression of the enzymes was restored and was comparable to levels of expression observed in immature animals. These results are important to other scientists because they show that gene expression and enzyme activity are not corresponding events during pubertal development in the rat.

Technical Abstract: We investigated mRNA expression of 3beta-hydroxysteroid dehydrogenase/D5-4 isomerase (3beta HSD) and cytochrome P450 17alpha-hydroxylase/C17-20 lyase (P45017a) by in situ hybridization to understand the basis for changes in steroidogenesis known to occur during sexual maturation in the rat. These results were compared to their respective enzyme activities, immunoexpression of 3bHSD protein, and plasma testosterone. Amounts of 3bHSD and P45017a mRNAs were age dependent; both transcripts were expressed abundantly by clusters of immature Leydig cells in 21 and 28 day old animals. During sexual maturation, mRNA for 3bHSD and P45017a decreased to undetectable levels at 45 and 60 and at 60 days of age, respectively, even though large populations of Leydig cells immunostained for 3bHSD protein. In the adult testis, 90 days of age, expression of 3bHSD and P450 17alpha transcripts rebounded and were comparable to levels of expression observed in immature animals. Enzyme activities per testis for 3bHSD and P450 were inversely related to mRNA expression the pubertal phase of development. Enzyme activities for 3bHSD and P45017a peaked at 60 and 45 days of age, respectively. These results show that gene expression and enzyme activity are not corresponding events during pubertal development in the rat. Moreover, these data suggest that expression of 3bHSD and P45017a gene transcripts are regulated differentially during development.