Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes
The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2011-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/16/12/9983/ |
| _version_ | 1818979745798291456 |
|---|---|
| author | Leping Ye Ren-Shan Ge Zhi-Jian Su |
| author_facet | Leping Ye Ren-Shan Ge Zhi-Jian Su |
| author_sort | Leping Ye |
| collection | DOAJ |
| description | The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1) for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant constituents (genistein and gossypol). This paper reviews these endocrine disruptors targeting steroidogenic enzymes. |
| first_indexed | 2024-12-20T17:04:25Z |
| format | Article |
| id | doaj.art-803a1c0e5f634b73aca355fe15cb8976 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-20T17:04:25Z |
| publishDate | 2011-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-803a1c0e5f634b73aca355fe15cb89762022-12-21T19:32:22ZengMDPI AGMolecules1420-30492011-12-01161299831000110.3390/molecules16129983Inhibitors of Testosterone Biosynthetic and Metabolic Activation EnzymesLeping YeRen-Shan GeZhi-Jian SuThe Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1) for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant constituents (genistein and gossypol). This paper reviews these endocrine disruptors targeting steroidogenic enzymes.http://www.mdpi.com/1420-3049/16/12/9983/endocrine disruptorsteroidogenic enzymessteroidogenic inhibitorsLeydig cellsmale reproduction |
| spellingShingle | Leping Ye Ren-Shan Ge Zhi-Jian Su Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes Molecules endocrine disruptor steroidogenic enzymes steroidogenic inhibitors Leydig cells male reproduction |
| title | Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes |
| title_full | Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes |
| title_fullStr | Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes |
| title_full_unstemmed | Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes |
| title_short | Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes |
| title_sort | inhibitors of testosterone biosynthetic and metabolic activation enzymes |
| topic | endocrine disruptor steroidogenic enzymes steroidogenic inhibitors Leydig cells male reproduction |
| url | http://www.mdpi.com/1420-3049/16/12/9983/ |
| work_keys_str_mv | AT lepingye inhibitorsoftestosteronebiosyntheticandmetabolicactivationenzymes AT renshange inhibitorsoftestosteronebiosyntheticandmetabolicactivationenzymes AT zhijiansu inhibitorsoftestosteronebiosyntheticandmetabolicactivationenzymes |