Diethylstilbestrol Versus Estradiol: DISCUSSION(2)
Because AFP in most rodents is an effective binder of E2 but not of DES, reduced bioavailability of perinatally administered E2 would seem to be a reasonable explanation for its lower potency as a perinatal ED agent compared to DES. However, that cannot be the case for the differential ED potency of E2 versus DES in the hamster, because hamster AFP is like that in humans, which does not bind E2.
An alternative explanation stems from various in vitro and in vivo assays showing that DES is inherently more estrogenic than E2. Of course, in a whole animal, the relative potency of such agents is influenced by a web of complex biological and pharmacokinetic dynamics, such as the method of agent administration (e.g., s.c. injection compared to the more “natural,” oral route), developmental stage, metabolic activation/clearance, and influence of serum-binding proteins other than AFP (e.g., albumin, sex hormone-binding globulin). For instance, a finding relevant to the latter topic is that albumin does bind DES preferentially to E2 in rats and hamsters. Also, preliminary observations (unpublished results) indicate that the conjugated estrogen, E2-benzoate, more closely mimics the neonatal ED action of DES in the male and female hamster than does the natural ovarian estrogen, E2.