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 intracellular cAMP. The latter...

Prostate Cancer

The expansion of prostate cancer screening efforts in the United States during the mid 1980s, Table 1.1 Examples of Candidate Genes in Five Hormone-Related Cancers Table 1.1 Examples of Candidate Genes in Five Hormone-Related Cancers FSH, progesterone, inhibin B Testosterone (dihydrotestosterone) LH, estrogen CYP17, HSD17B3, HSD17B4, HSD17B5, SRD5A2, AR CYP17, cytochrome P-450 17,20 lyase CYP19, aromatase HSD17B1, 17 -hydroxysteroid dehydrogenase type I ER, estrogen receptor PR, progesterone...

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. Imperial Cancer Research Fund Cancer Epidemiology Unit University of Oxford Radcliffe Infirmary Oxford, United Kingdom David J. Bentrem, M.D. Department of Surgery and Molecular Pharmacology Northwestern University Medical School Robert H. Luire Comprehensive Cancer...

Regulation Of 173hydroxysteroid Dehydrogenase 1 Expression

Besides genetic alterations, abnormal regulation of gene transcription can result in changed protein expression and biological response. An example is the mouse gene for 17HSD8, also known as the ke6 gene, in which no nucleotide alterations have been detected but lack of the regulatory protein of which probably results in recessive polycystic kidney disease.47 To elucidate the mechanisms resulting in the expression, or possible overexpression, of 17HSD1, regulation of HSD17B1 expression in...

Expression in Breast Cancer

Estrogen levels are consistently elevated in breast tissue of cancer patients compared to normal individuals.53,54 The presence of a breast tumor enhances the local expression of aromatase three- to fourfold in the surrounding breast adipose tissue, to levels equivalent to those within the tumor itself. Furthermore, there is a gradient of aromatase expression with the tumor as its focus.55-57 Breast tumors produce factors that stimulate the proliferation of mesenchymal cells surrounding them,...

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...

T187m R227q F234l F194l

Peat polymorphism in the 3'-untranslated region. Constitutional DNA missense substitutions are identified below the gene in the single-letter amino acid code. tein, others resulted in either increases or decreases in enzyme kinetics. One in particular, an alanine-to-threonine substitution at codon 49 (A49T), resulted in a substantial increase in enzyme activity. Although uncommon in healthy control men, the Reichardt group assessed its possible role in prostate cancer etiology in a multiracial...

Orchiectomy

Surgical castration, most commonly achieved with bilateral subcapsular orchiectomy, was one of the first forms of therapy available for prostate cancer. Its continued use in the twenty-first century identifies it as the clinical former standard against which newer hormonal therapies must be compared.23 Surgical castration results in a rapid fall in serum T concentration to 0 -10 Table 19.1 Hormonal Therapies of Proven or Potential Use in Prostate Cancer Surgical therapy Orchiectomy...

HSD3B1 and HSD3B2

The enzyme 3 -hydroxysteroid dehydrogen-ase is a critical component of the androgen-me-tabolism pathway because it catalyzes andros-tendione production in steroidogenic tissues and converts active DHT into inactive metabolites in steroid target tissues. The HSD3B gene family has two genes and five pseudogenes, all of which map to chromosome 1p13.92-94 The HSD3B1 gene encodes the type I enzyme, which is exclusively expressed in the placenta and peripheral tissues, such as prostate, breast, and...

Genetic Basis Of Hormonal Carcinogenesis

The identification and genetic characterization of families at high risk of breast cancer is the most striking example of the potential importance of inherited traits in breast cancer causation. The localization and sequencing of BRCA1 and BRCA2 has provided two important genes contributing to familial breast and ovarian can-cer.24,25 Somewhat surprisingly, mutations in these genes, which appear to be classic tumor-suppressor genes, seem to contribute little, if at all, to the causative pathway...