CYTOCHROME-P450S IN THE GUINEA-PIG ADRENAL THAT ARE IMMUNOLOGICALLY SIMILAR TO LIVER FORMS - ESTROGEN SUPPRESSION EXPLAINS MALE-FEMALE DIFFERENCES

被引:3
作者
BLACK, VH [1 ]
机构
[1] NYU, SCH MED, KAPLAN CANC CTR, NEW YORK, NY 10016 USA
关键词
D O I
10.1016/0960-0760(92)90313-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several cytochrome P450s have been identified in guinea pig adrenal microsomes which are distinct from the known steroidogenic P450s, c17 and c21, and are immunochemically related to cytochrome P450s found in liver. One, a 52 K protein related to P450 I (CYP1), occurs almost exclusively in males, is localized to the inner zone, and is suppressed by ACTH. Its levels correlate with microsomal capacity for xenobiotic metabolism. The others, related to P450s II and Ill (CYP2 and 3), are more predominant in males, but not exclusive to them, are found in both the inner and outer zones, and are not suppressed by ACTH. Their functions remain to be elucidated. The male predominance of the CYP1-related protein has recently been shown to be due to suppression of the protein in females by estrogen. To determine if estrogen is also involved in the regulation of the CYP2-related proteins, ovariectomized and sham-operated animals were treated with a long-acting estrogen, estradiol valerate, or with the vehicle alone. These P450s reached male levels in ovariectomized females treated only with the vehicle. Their enhanced levels were suppressed by treatment with estrogen. Estrogen treatment also suppressed the levels of the P450s seen in sham-operated females. Endogenous estrogen produced similar effects. In hemi-ovariectomized females the contralateral ovary hypertrophied, a state in which estrogen levels would be maintained or increased. In these females no increase occurred in the immunodetectable P450s. In normal females, estrogen levels are low in prepubertal animals, rise at the time of puberty and drop again after ovarian cycling is completed. The CYP2-related proteins were present in adrenal microsomes of prepubertal females, but were suppressed after puberty. On the other hand, post-estrous females, in whom estrogen levels would be low, acquired male levels of these proteins in their adrenal microsomes. P450c17 and P450c21, as well as 3beta-hydroxysteroid dehydrogenase, were not affected by surgery or estrogen. Taken together, these experiments indicate that suppression by estrogen in females can account, in large part, for the predominance of several immunochemical homologs of liver P450s in adult male guinea pig adrenals.
引用
收藏
页码:863 / 868
页数:6
相关论文
共 22 条
[1]   ESTRADIOL METABOLISM BY COMPLEMENTARY DEOXYRIBONUCLEIC ACID-EXPRESSED HUMAN CYTOCHROME-P450S [J].
AOYAMA, T ;
KORZEKWA, K ;
NAGATA, K ;
GILLETTE, J ;
GELBOIN, HV ;
GONZALEZ, FJ .
ENDOCRINOLOGY, 1990, 126 (06) :3101-3106
[2]  
BLACK V H, 1990, Journal of Cell Biology, V111, p462A
[3]   IMMUNODETECTABLE CYTOCHROMES-P450-I, CYTOCHROME-P-450-II, AND CYTOCHROME-P-450-III IN GUINEA-PIG ADRENAL-HORMONE RESPONSIVENESS AND RELATIONSHIP TO CAPACITY FOR XENOBIOTIC METABOLISM [J].
BLACK, VH .
ENDOCRINOLOGY, 1990, 127 (03) :1153-1159
[4]   EFFECTS OF AGE, ADRENOCORTICOTROPIN, AND DEXAMETHASONE ON A MALE-SPECIFIC CYTOCHROME-P450 LOCALIZED IN THE INNER ZONE OF THE GUINEA-PIG ADRENAL [J].
BLACK, VH ;
BARILLA, JR ;
MARTIN, KO .
ENDOCRINOLOGY, 1989, 124 (05) :2494-2498
[5]   A CYTOCHROME-P450 IMMUNOCHEMICALLY RELATED TO P450C,D (P450I) LOCALIZED TO THE SMOOTH MICROSOMES AND INNER ZONE OF THE GUINEA-PIG ADRENAL [J].
BLACK, VH ;
BARILLA, JR ;
RUSSO, JJ ;
MARTIN, KO .
ENDOCRINOLOGY, 1989, 124 (05) :2480-2493
[7]   ESTRADIOL 16-ALPHA-HYDROXYLATION IN THE MOUSE CORRELATES WITH MAMMARY-TUMOR INCIDENCE AND PRESENCE OF MURINE MAMMARY-TUMOR VIRUS - A POSSIBLE MODEL FOR THE HORMONAL ETIOLOGY OF BREAST-CANCER IN HUMANS [J].
BRADLOW, HL ;
HERSHCOPF, RJ ;
MARTUCCI, CP ;
FISHMAN, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (18) :6295-6299
[8]   EXPRESSION AND FUNCTION OF 3 CYTOCHROME-P-450 ISOZYMES IN RAT EXTRAHEPATIC TISSUES [J].
CHRISTOU, M ;
WILSON, NM ;
JEFCOATE, CR .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1987, 258 (02) :519-534
[9]   ADRENAL-GLAND TOXICITY - CHEMICALLY-INDUCED DYSFUNCTION [J].
COLBY, HD .
JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, 1988, 7 (01) :45-69
[10]   DIFFERENTIAL CONTROL OF ADRENAL DRUG AND STEROID METABOLISM IN GUINEA-PIG [J].
GREINER, JW ;
KRAMER, RE ;
RUMBAUGH, RC ;
COLBY, HD .
LIFE SCIENCES, 1977, 20 (06) :1017-1026