Lactogen and LH receptors. Rat P-450 17 alpha, structural analysis and hormonal regulation of mRNA levels in the Leydig cell.

Abstract:

:A complete amino acid sequence for rat testis P-450 17 alpha was deduced from nucleotide analysis of a cDNA clone isolated from a rat Leydig cell library. This cDNA expressed in COS-1 cells both 17 alpha-hydroxylase and 17,20 lyase activities. Rat P-450 17 alpha exhibited significant similarity to the nucleotide and deduced amino acid sequences of the bovine and human P-450 17 alpha, particularly with the highly conserved regions and secondary structure. The rat P-450 17 alpha is anchored to the ER by two transmembrane regions: the N-terminal insertion peptide and the stop-transfer sequence. The C-terminal is associated with the ER by four hydrophobic clefts including the steroid-binding site. We have demonstrated a dual effect of hCG, causing early increases of Leydig cell P-450 17 alpha mRNA levels at low doses, while higher desensitizing doses caused marked subsequent reduction of mRNA levels. Our studies demonstrate that gonadotropin stimulation and desensitization of P-450 17 alpha dependent enzymes (17 alpha-hydroxylase/17,20 desmolase) in the adult rat testis and E2 induced desensitization in fetal Leydig cells are related to levels of P-450 17 alpha mRNA.

journal_name

Ann N Y Acad Sci

authors

Dufau ML,Minegishi T,Buczko E,Kitamura M,Delgado C,Namiki M

doi

10.1111/j.1749-6632.1989.tb25888.x

subject

Has Abstract

pub_date

1989-01-01 00:00:00

pages

57-76

eissn

0077-8923

issn

1749-6632

journal_volume

564

pub_type

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