Regulation of Cholesterol to Pregnenolone Conversion

P450scc plays a key role in carrying out the conversion of cholesterol to pregnenolone and is subject to many levels of regulation. In the adrenal, gonads, and placenta, P450scc is regulated by various tropic hormones, utilizing cAMP or calcium as intracellular messengers.12 Steroid hormone biosynthesis in the adrenals is stimulated by the pituitary hormone corticotropin, which binds to its receptor at the cell surface and activates adenyl cyclase to increase intra-cellular cAMP. The latter...

Contributors

Department of Genetics and Medicine, Harvard Medical School Massachusetts General Hospital Director, Medical and Population Genetics, Whitehead MIT Center for Genome Research Boston, MA Emily Banks, M.B., B.S., B.Med.Sci., Ph.D. David J. Bentrem, M.D. Department of Surgery and Molecular Pharmacology Northwestern University Medical School Robert H. Luire Comprehensive Cancer Center Chicago, IL Philip Bretsky, M.P.H. Department of Preventive Medicine University of Southern California Keck School...

David J Bentrem V Craig Jordan

Prevention of disease is far superior to treating symptomatic illness. Until recently, the prevention of cancer focused on the identification of environmental carcinogens and the reduction of their exposure to the population. Education to avoid cigarette smoking is an example of primary prevention of lung cancer. Secondary prevention consists of screening individuals at increased risk for malignancy with the assumption that early detection and treatment will affect survival. Mammography and...

Glucocorticoid and Mineralocorticoid Receptors

Glucocorticoids are involved in a wide array of physiological responses, including regulation of glucose, lipid, and protein metabolism, stress response, immune function, and mood (Tables 3.4, 3.5). Given the wide array of responses that these hormones (produced primarily by the adrenal gland) elicit, it is not surprising that the GR is expressed widely and that its function has been extensively explored. As discussed above (see Crosstalk Between Nuclear Receptors and Other Transcription...

The 216aHydroxylated Estrogen Breast Cancer Risk Hypothesis

On the basis of the studies described above, which showed that increased formation of 16a-hydroxylated metabolites relative to 2-hydroxy-lated estrogen metabolites may be associated with an elevated risk of breast cancer, it was hypothesized that a low urinary 2-hydroxyestrone to 16a-hydroxyestrone ratio should be inversely associated with breast cancer risk.144 Development of a competitive-type enzyme immunoas-say (EIA) method for quantifying these metabolites in urine145 allowed the...

Hydroxysteroid Dehydrogenases In Breast Epithelial Cells

Both 17HSD1 and 17HSD2 are expressed in normal breast tissue,23,51 and recent investigations suggest that the oxidative (type 2) activity is the dominant form in nontumorous breast cells.51-53 In a study in which a total of 22 samples was analyzed, 17HSD1 protein was detected in most of the normal breast samples from women having regular menstrual cycles and in all samples from women using hormonal con-traception.23 The type 1 enzyme is expressed in epithelial cells of ducts and alveoli...

References

On the treatment of inoperable cases of carcinoma of the mamma suggestions for a new method of treatment with illustrative cases. Lancet 2 104, 1896. 2. Bittner JJ. The causes and control of mammary cancer in mice. Harvey Lect 42 221, 1946-1947. 3. Bittner JJ. The genesis of breast cancer in mice. Texas Rep Biol Med 10 160, 1952. 4. Rous P, Kidd JG. Conditional neoplasms and subthreshold neoplastic states. J Exp Med 73 365, 1941. 5. Berenblum I. Cocarcinogenesis. Br Med Bull 4 343,...

Italian Study

The third tamoxifen prevention study, performed in Italy, began in October 1992 and randomized 5408 women aged 35-70 to 20 milligrams of tamoxifen or placebo daily for 5 years.161 Originally, 20,000 volunteers without risk factors were sought, but the study was stopped prematurely because of poor recruitment and compliance. Women were required to have had a hysterectomy for a nonneoplastic condition to obviate concerns about an increased risk of endometrial carcinoma. There was no requirement...

Info

The Marsden group extensively studied gynecological complications associated with tamox-ifen treatment in healthy women. Since ovarian and uterine assessment by transvaginal ultrasound became available some time after the trial's start, many subjects did not have a baseline evaluation. Ovarian screening demonstrated a significantly increased risk (p < 0.005) of benign ovarian cysts in premenopausal women who had received tamoxifen for more than 3 months compared to controls. There were no...

Raloxifene

Figure 12.11 Comparison of the molecular structures of new and established selective estrogen receptor modulators. ance, 2 not be cross-resistant with tamoxifen, and 3 have fewer side effects such as a lower incidence of endometrial cancer observed with tamoxifen. Steroidal antiestrogens have been developed and have proven to be antiestrogenic in all target tissues206 through premature destruction of the ER.207,208 The pure antiestrogens are effective in laboratory models as second-line...