In:
Reproduction, Fertility and Development, CSIRO Publishing, Vol. 13, No. 4 ( 2001), p. 297-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1031-3613
Language:
English
Publisher:
CSIRO Publishing
Publication Date:
2001
SSG:
12
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