The intracrine sex steroid biosynthesis pathways.
There is an increasing number of differences reported between the steroidogenesis pathways described in the traditional literature related to gonadal steroidogenesis and the more recent observations achieved using new technologies, especially molecular cloning, pangenomic expression studies, precise quantification of mRNA expression using real-time PCR, use of steroidogenic enzymes stably transfected in cells, detailed enzymatic activity analysis in cultured cell lines and mass spectrometry analysis of steroids. The objective of this chapter is to present steroidogenesis in the light of new findings that demonstrate pathways of biosynthesis of estradiol (E(2)) and dihydrotestosterone (DHT) from adrenal dehydroepiandrosterone (DHEA) in peripheral intracrine tissues which do not involve testosterone as intermediate as classically found in the testis and ovary. Steroidogenic enzymes different from those of the ovary and testis act in a tissue-specific manner to catalyze the transformation of DHEA into active sex steroids. These new pathways are especially important in post-menopausal women where all estrogens and practically all androgens are made at their site of action in peripheral tissues from DHEA, the precursor of adrenal origin. In men, on the other hand, from 40 to 50% of androgens are made in peripheral tissues from adrenal DHEA, thus indicating the major importance of the intracrine pathways in both men and women. We also examine the molecular evolution of steroidogenic enzymes which explains the major differences in steroid metabolism observed between laboratory animals and humans.
Luu-The
Van
V
Oncology, Molecular Endocrinology and Human Genomics Research Center (CREMOGH), Department of Molecular Medicine, Laval University and Laval University Hospital Research Center (CRCHUL), Quebec, Canada. Van.Luu-The@crchul.ulaval.ca <Van.Luu-The@crchul.ulaval.ca>
Labrie
Fernand
F
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000311:Adrenal Glands / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D003687:Dehydroepiandrosterone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis* / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D010053:Ovary / Q000737:chemistry / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000145:classification / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000737:chemistry / Q000378:metabolism
D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3; D013250:Steroid Hydroxylases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase