We have previously found that several families of nonpolar short chain 11β-ethers and esters ofestradiol are selective estrogen receptor modulators （SERMs）. Surprisingly, the transformation from potent estrogen to ...We have previously found that several families of nonpolar short chain 11β-ethers and esters ofestradiol are selective estrogen receptor modulators （SERMs）. Surprisingly, the transformation from potent estrogen to anti-estrogen occurs when the 11β-side chain is increased slightly in length from four to five non-hydrogen atoms. To generate strong antagonists for preclinical development, we have synthesized other similar ER ligands with 11β-ethers and with an additional ethinyl group at the 17β-position in order to slow metabolism of the steroidal moiety. Here we report the synthesis and biological activity of two such compounds （11β-i-PrO-propyl and 11β-t-BuO-propyl ethers） with extremely strong antagonist activities.展开更多
Objective: To study the effect of Chineseherbal medicine for replenishing Kidney combined with acupuncture in treating anovulationand infertility, and the relationship betweenits ovulation inducing effect and endometr...Objective: To study the effect of Chineseherbal medicine for replenishing Kidney combined with acupuncture in treating anovulationand infertility, and the relationship betweenits ovulation inducing effect and endometrialcontents of estradiol receptor (ER) and progesterone receptor (PR). Methods: Twentynine cases were treated with replenishing Kidney drugs combined with acupuncture for 1～3months. Patients' ER and PR were measuredby immunohistochemical method. And pa- tients were classified according to PR contentinto PR positive group and mild PR positivegroup. Results: Fifteen cases of PR positivegroup, completed treatment for 45 cycles, among them, 40 cycles showed ovulation, theovulation rate being 88. 89 %. Ten in 14 cases, who complicated with infertility, becamepregnant, the pregnant rate being 71. 43%.While in 11 cases of Ph mild positive group, 9complicated with in fertility, completed treatment for 33 cycle, 10 cycles showed ovulation(30. 30 % ), and pregnant rate 22. 22 % (2/9). The difference between the two groupswas significant (P < 0. 01 ). Conclusion: Thereplenishing Kidney drugs combined withacupuncture treatment could result a good effect in treating infertility due to anovulation,especially on those with high endometrial PRcontent.展开更多
OBJECTIVE: To investigate the hormone-like activities of Kuntai capsule(KTC) in the uteri of ovariectomized rats and immature rabbits.METHODS: Following bilateral ovariectomy, rats were randomly divided into six group...OBJECTIVE: To investigate the hormone-like activities of Kuntai capsule(KTC) in the uteri of ovariectomized rats and immature rabbits.METHODS: Following bilateral ovariectomy, rats were randomly divided into six groups including sham group, control group, estradiol valerate group, KTC 0.24, 0.6, and 1.5 g/kg groups. The rats were treated with 0.5% CMC-Na, estradiol valerate and KTC(0.24, 0.6, and 1.5 g/kg), respectively for 28 consecutive days. Then the estrous cycle, uterine changes and pathological changes were examined.Serum levels of estradiol(E2), and progesterone(P4)were measured by enzyme-linked immunosorbent assay(ELISA). Protein levels of estradiol receptor(ER), progesterone receptor(PR), vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA) and nuclear-associated antigen-67(Ki-67) in uterine tissues were detected by western blot. Immature rabbits were estrogen-primed prior to intragastric administration with KTC for 6 d consecutively. Then, the uteri underwent hematoxylin-eosin staining to observe endometrial transformation.RESULTS: Compared with the control group, 0.6and 1.5 g/kg KTC markedly decreased the uterine organ coefficient and endometrial thickness(P <0.05). The serum level of P4 was increased in the KTC 0.6 g/kg group(P < 0.05). There were no significant variations in the serum level of E2 in the KTC groups compared with the control group. ERβ, but not ERα, was markedly upregulated after KTC administration(P < 0.05). Furthermore, 1.5 g/kg KTC significantly decreased the protein level of PRA(P <0.05) and 0.6 g/kg KTC increased the protein level of PRB in the uteri(P < 0.05). VEGF was highly expressed after treatment with 0.24 and 0.6 g/kg KTC,and Ki-67 was markedly reduced in ovariectomized rats treated with 1.5 g/kg KTC. No difference was found in the expression of PCNA. KTC 0.24 and0.6 g/kg promoted endometrial transformation in immature rabbit uteri.CONCLUSION: KTC does not demonstrate obvious estrogen-like effect on uteri after ovariectomy, but it does exhibit weak progestogen-like effect, by which mechanism of action is yet to be further investigated.展开更多
文摘We have previously found that several families of nonpolar short chain 11β-ethers and esters ofestradiol are selective estrogen receptor modulators （SERMs）. Surprisingly, the transformation from potent estrogen to anti-estrogen occurs when the 11β-side chain is increased slightly in length from four to five non-hydrogen atoms. To generate strong antagonists for preclinical development, we have synthesized other similar ER ligands with 11β-ethers and with an additional ethinyl group at the 17β-position in order to slow metabolism of the steroidal moiety. Here we report the synthesis and biological activity of two such compounds （11β-i-PrO-propyl and 11β-t-BuO-propyl ethers） with extremely strong antagonist activities.
文摘Objective: To study the effect of Chineseherbal medicine for replenishing Kidney combined with acupuncture in treating anovulationand infertility, and the relationship betweenits ovulation inducing effect and endometrialcontents of estradiol receptor (ER) and progesterone receptor (PR). Methods: Twentynine cases were treated with replenishing Kidney drugs combined with acupuncture for 1～3months. Patients' ER and PR were measuredby immunohistochemical method. And pa- tients were classified according to PR contentinto PR positive group and mild PR positivegroup. Results: Fifteen cases of PR positivegroup, completed treatment for 45 cycles, among them, 40 cycles showed ovulation, theovulation rate being 88. 89 %. Ten in 14 cases, who complicated with infertility, becamepregnant, the pregnant rate being 71. 43%.While in 11 cases of Ph mild positive group, 9complicated with in fertility, completed treatment for 33 cycle, 10 cycles showed ovulation(30. 30 % ), and pregnant rate 22. 22 % (2/9). The difference between the two groupswas significant (P < 0. 01 ). Conclusion: Thereplenishing Kidney drugs combined withacupuncture treatment could result a good effect in treating infertility due to anovulation,especially on those with high endometrial PRcontent.
文摘OBJECTIVE: To investigate the hormone-like activities of Kuntai capsule(KTC) in the uteri of ovariectomized rats and immature rabbits.METHODS: Following bilateral ovariectomy, rats were randomly divided into six groups including sham group, control group, estradiol valerate group, KTC 0.24, 0.6, and 1.5 g/kg groups. The rats were treated with 0.5% CMC-Na, estradiol valerate and KTC(0.24, 0.6, and 1.5 g/kg), respectively for 28 consecutive days. Then the estrous cycle, uterine changes and pathological changes were examined.Serum levels of estradiol(E2), and progesterone(P4)were measured by enzyme-linked immunosorbent assay(ELISA). Protein levels of estradiol receptor(ER), progesterone receptor(PR), vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA) and nuclear-associated antigen-67(Ki-67) in uterine tissues were detected by western blot. Immature rabbits were estrogen-primed prior to intragastric administration with KTC for 6 d consecutively. Then, the uteri underwent hematoxylin-eosin staining to observe endometrial transformation.RESULTS: Compared with the control group, 0.6and 1.5 g/kg KTC markedly decreased the uterine organ coefficient and endometrial thickness(P <0.05). The serum level of P4 was increased in the KTC 0.6 g/kg group(P < 0.05). There were no significant variations in the serum level of E2 in the KTC groups compared with the control group. ERβ, but not ERα, was markedly upregulated after KTC administration(P < 0.05). Furthermore, 1.5 g/kg KTC significantly decreased the protein level of PRA(P <0.05) and 0.6 g/kg KTC increased the protein level of PRB in the uteri(P < 0.05). VEGF was highly expressed after treatment with 0.24 and 0.6 g/kg KTC,and Ki-67 was markedly reduced in ovariectomized rats treated with 1.5 g/kg KTC. No difference was found in the expression of PCNA. KTC 0.24 and0.6 g/kg promoted endometrial transformation in immature rabbit uteri.CONCLUSION: KTC does not demonstrate obvious estrogen-like effect on uteri after ovariectomy, but it does exhibit weak progestogen-like effect, by which mechanism of action is yet to be further investigated.
