Interaction of ring B unsaturated estrogens with estrogen receptors of human endometrium and rat uterus

During development, 17alpha-estradiol is a potent estrogen and carcinogen.

“…This study demonstrated that neonatal treatment with E2-177a can induce teratogenic and morphological changes equivalent observed when compared to E2-17P (20).…”

B-Ring unsaturated estrogens: biological evaluation of 17α-Dihydroequilein and novel B-Nor-6-thiaequilenins as tissue selective estrogens

“…In 1991, Bhavnani and co-workers examined a number of ring B unsaturated steroids in their unconjugated form in order to determine their relative binding affinities for the estrogen receptor and their in vivo effects on uterine hypertrophy in ovary-intact rats. 2 All of the individual equine components caused an increase in uterine wet weight with the exception of 4 which lacked a significant effect at the highest dose tested. More recently, the sulfate ester conjugate of 17a-DHEqn has been shown to lower serum cholesterol, 3 increase hippocampal dendritic spine density in rats, 4 and improve arterial vasomotor function in macaques.…”

“…The trend we observe for 1-4 is consistent with data previously reported in ovary-intact rats although in these studies 17a-DHEqn did not induce uterine weight gain after daily subcutaneous administration of 2 mg/kg for 3 days. 2 In order to assess whether 4 antagonizes the effects of estrogen in the uterus it was evaluated in ovary-intact rats that were co-administered with test compound and ethynyl estradiol (EE2, 0.1 mpk) for three days. As shown in Table 1, the known pure antagonist ICI 182,780 8 effectively blocks the stimulatory response of EE2 in a dose dependent manner.…”

“…The biological effects of modifying the C-17 hydroxy group of CEEs and other estrogens has been well documented. 2 We were specifically interested in how alterations at the C/D ring juncture with respect to the C-17 hydroxyl group might influence receptor affinity and, ultimately, uterine pharmacology. However, due to the synthetic complexity involved in the enantioselective preparation of such derivatives, we chose to investigate the benzothiophene, or B-nor-5-thiaequilenin, scaffold.…”

Mechanisms of Cardioprotection by Estrogens

“…The identity and biological activities of these polar metabolites are only beginning to be investigated. 17p-dihydroequilin sulphate is a far greater uterotrophic agent than equilin (12) and has one of the highest binding affinities for estrogen receptors (13) in the human and rat uterus, but in the rabbit uterus all the equine estrogens were less effective than 17 P-estradiol, but better than 17a-estradiol (12). Howard and Keaty (14) examined the clinical potency of CEE components using suppression of urinary gonadotrophic levels in oopherectomized women.…”