Endocrine regulation of cytochrome P-450 in the rat brain and pituitary gland.
In an effort to understand the physiological functions of cytochrome P-450 in the central nervous system and pituitary gland, we evaluated changes in the level of the enzyme as a function of the endocrine status of rats and the ability of these tissues to synthesize or degrade steroids. The P-450 content of microsomes prepared from the hypothalamic preoptic area (HPOA), the olfactory lobes and the cerebrum was 0.040 +/- 0.009 and in the pituitary gland 2.2 +/- 0.6 (S.D.) nmol/g tissue. The P-450 content of the HPOA and olfactory lobes, but not of the rest of the cerebrum, was influenced by the endocrine status of rats. In microsomes it increased five- to tenfold over control levels during late pregnancy in the olfactory lobes and during lactation in the HPOA, and in both brain regions treatment of rats with 5 alpha-dihydrotestosterone (DHT) caused an eight- to tenfold increase in the P-450 content. Androstenedione was not a good substrate for brain P-450. The level of androstenedione 19-hydroxylase in the olfactory lobe microsomal fraction was 0.50 +/- 0.06 nmol 19-hydroxyandrostenedione formed/g tissue per h. This activity was tenfold lower in other brain areas and was not detectable in the pituitary gland. The rate of aromatization of androstenedione to oestradiol in the HPOA and olfactory lobe of lactating rats was 0.46 +/- 0.14 and 0.38 +/- 0.05 pmol/oestradiol formed/g tissue per h respectively. 5 alpha-Androstane-3 beta,17 beta-diol (A-5 alpha-3 beta,17 beta-diol) was a much better substrate for P-450 throughout the brain and pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
M
M
Warner
P
P
Tollet
M
M
Strömstedt
K
K
Carlström
J A
JA
Gustafsson
D043582:5-alpha-Dihydroprogesterone; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology*; D011277:Pregnanediones / Q000494:pharmacology*; D011301:Preoptic Area / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D011277:Pregnanediones; D003577:Cytochrome P-450 Enzyme System; D043582:5-alpha-Dihydroprogesterone