Estrogen sulfamates: a new approach to oral estrogen therapy
| Autor: | Michael Dr Oettel, A. Barth, Birgitt Schneider, J. Züchner, K. Müller, Gudrun Reddersen, Sigfrid Prof-Dr Schwarz, W. Elger, Annemarie Hedden, P. Ritter, E. Krahl |
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| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Estrone medicine.drug_class medicine.medical_treatment Cmax Administration Oral Estrogen receptor Reproductive technology Biology Steroid chemistry.chemical_compound Endocrinology Estrone sulfate Internal medicine Tumor Cells Cultured Genetics medicine Animals Bile Prodrugs Rats Wistar Molecular Biology Sulfonamides Estradiol Estrogens Rats Perfusion Liver Receptors Estrogen Reproductive Medicine chemistry Estrogen Female Animal Science and Zoology Folliculogenesis hormones hormone substitutes and hormone antagonists Developmental Biology Biotechnology |
| Zdroj: | Reproduction, Fertility and Development. 13:297 |
| ISSN: | 1031-3613 |
| DOI: | 10.1071/rd01029 |
| Popis: | Sulfamate substitution (-O-SO 2-NH 2) at carbon atom 3 of the steroid skeleton leads to orally active prodrugs of estrogens with much higher systemic, but lower hepatic, estrogenic activity than their parent steroids. This dissociation is achieved by first passage through the liver in erythrocytes, followed by systemic hydrolysis which releases the ‘parent’ estrogen. In the rat, orally administered tritiated estradiol sulfamate, unlike estradiol, appears in the circulation at high concentrations. At C max , approximately one third of the administered dose forms a depot in the circulation (98% in erythrocytes, 2% in plasma). Significant estradiol, estrone and estrone sulfate concentrations were recorded in plasma during depletion of the red blood cell pool. Estradiol sulfamate (J995) has no estrogen receptor affinity per se or estrogenic activity in vitro ( i.e. without hydrolysis). Its oral uterotropic activity in rats is approximately 100 times greater than that of estradiol, however, its hepatotropic activity is only marginally elevated. These functions include bile secretion, the secretion of angiotensinogen, lipoproteins (total and high-density lipoprotein cholesterol) and insulin-like growth factor I (IGF-I). Orally administred estradiol sulfamate led to systemic estrogenic effects without significant hepatic responses, whereas estradiol and other ‘conventional’ estrogens exerted parallel systemic and hepatic estrogenic effects. Sulfamate technology represents an approach to the use of natural estrogens for fertility control and hormone replacement therapy in both genders. In this context, reduced effects on hemostatic factors, angiotensinogen, bile and IGF-I secretion seem the most important aspects. In addition, blood concentrations of estrogens are less variable than with conventional estrogens. |
| Databáze: | OpenAIRE |
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