Identification of a rat adrenal cytochrome P450 active in polycyclic hydrocarbon metabolism as rat CYP1B1. Demonstration of a unique tissue- specific pattern of hormonal and aryl hydrocarbon receptor-linked regulation

Ovarian stimulation and granulosa-cell tumour

A novel ACTH-inducible P450, cytochrome P450RAP, is responsible for polycyclic aromatic hydrocarbon (PAH) metabolism in male rat adrenal microsomes. P450RAP is present at similar levels in male and female adrenal microsomes and is immunochemically distinct from P450IA1. Anti-P450RAP immunoblots a protein present in ovarian and testicular microsomes that is the same size as P450RAP and which coelutes with the P450 fraction during chromatography on an immobilized artificial membrane column made with phosphatidylcholine. Rat adrenal, ovarian, and testicular microsomes exhibit similar regioselectivities in the metabolism of two polycyclic aromatic hydrocarbons, dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (BP). Unlike P450IA1, these microsomes form little or no 7-OH-DMBA and BP-4,5-diol but do catalyze the formation of a high proportion of the presumptive procarcinogen, DMBA-3,4-diol. The relative activities of PAH metabolism by untreated adrenal, testicular, and ovarian microsomes are approximately 60...

Polycyclic aromatic hydrocarbon metabolism in rat adrenal, ovary, and testis microsomes is catalyzed by the same novel cytochrome P450 (P450RAP)

A propos de la fertilisation in vitro: problemes de la stimulation folliculaire, risques possibles de cancer par stimulation ovarienne excessive, cas publies de cancers de l'ovaire au cours du traitement, approche individualisee du traitement

https://www.bmj.com/content/bmj/299/6694/309.full.pdf

Follicular stimulation for high tech pregnancies: are we playing it safe?

Epidemiology, etiology, and fertility drugs in ovarian epithelial carcinoma: Where are we today?

1. The metabolism of 7,12-dimethylbenz(a)anthracene (DMBA) by primary cultures of human ovarian cells has been studied to identify the cell type(s) responsible for biotransformation of this carcinogen. The rate of DMBA metabolism was maximal in granulosa cells prestimulated in vivo with antiestrogen, hMG (human menopausal gonadotropin) and hCG (human chorionic gonadotropin), i.e., treatments required for maximal oocyte maturation and, thus, granulosa cell proliferation. In cells from unstimulated ovaries, the metabolism was maximal in granulosa-lutein cells isolated from corpus luteum.2. Steroid (progesterone and estradiol) levels were determined in the spent culture media or in media in parallel with DMBA metabolism to find out whether elevated steroid levels in vivo are required for the rapid metabolism of DMBA. In granulosa cell cultures from stimulated cycles, the concentrations of both progesterone and estradiol were at least 2 or 3 times higher, respectively, than in any of the other cell types test...

Lars Hamberger

Papers

Metabolism of 7,12-Dimethylbenz(a)Anthracene by Different types of Cells in the Human Ovary