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Lactogen and LH Receptors. Rat P‐450 17α , Structural Analysis and Hormonal Regulation of mRNA Levels in the Leydig Cell
Author(s) -
DUFAU MARIA L.,
MINEGISHI TAKASHI,
BUCZKO ELLEN,
KITAMURA MASAYA,
DELGADO CARLOS,
NAMIKI MIKIO
Publication year - 1989
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1989.tb25888.x
Subject(s) - pediatric endocrinology , medicine , endocrinology , gynecology
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.